Trial Outcomes & Findings for Low-dose Intra-arterial Bevacizumab for Edema and Radiation Necrosis Therapeutic Intervention (LIBERTI) (NCT NCT02819479)
NCT ID: NCT02819479
Last Updated: 2022-05-24
Results Overview
Imaging response to therapy will be quantitatively assessed on MRI using volumetric analysis. Regions of T2 and FLAIR prolongation above contralateral white matter will be calculated and quantified in cubic centimeters. Region of interest (ROI) will be created using a semi-automated, thresholding and region-growing technique. Enhancement of the lesion will be calculated using similar volumetric ROI analysis with a contrast threshold of 40% above background and measured in cubic centimeters.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
10 participants
Primary outcome timeframe
Baseline (before treatment), and 3 months and 12 months after single dose intra-arterial Avastin (bevacizumab)
Results posted on
2022-05-24
Participant Flow
Adults recruited from outpatient medical clinics at 2 academic medical centers (5 subjects per center) between Nov 2016 and Jan 2018. Enrollment was closed once 10 adult subjects were enrolled.
This was a single-arm study. There was no wash out or run-in period after enrollment. There was no assignment to groups.
Participant milestones
| Measure |
Low-dose Intra-arterial Bevacizumab
A single intra-arterial dose of 2.5 mg/kg bevacizumab will be administered after osmotic blood-brain-barrier disruption with intra-arterial 25% mannitol at rate of 4-12 ml/sec for 30 seconds.
25% Mannitol: Route of administration: In this study, the first step of the treatment will be performing osmotic blood-brain-barrier disruption with administration of intra-arterial 25% Mannitol into the appropriate cervical artery.
Low-dose Intra-arterial Bevacizumab: Route of administration:
In this study, the second step of the treatment will be administering intra-arterial bevacizumab into the appropriate cervical artery.
|
|---|---|
|
Overall Study
STARTED
|
10
|
|
Overall Study
COMPLETED
|
8
|
|
Overall Study
NOT COMPLETED
|
2
|
Reasons for withdrawal
| Measure |
Low-dose Intra-arterial Bevacizumab
A single intra-arterial dose of 2.5 mg/kg bevacizumab will be administered after osmotic blood-brain-barrier disruption with intra-arterial 25% mannitol at rate of 4-12 ml/sec for 30 seconds.
25% Mannitol: Route of administration: In this study, the first step of the treatment will be performing osmotic blood-brain-barrier disruption with administration of intra-arterial 25% Mannitol into the appropriate cervical artery.
Low-dose Intra-arterial Bevacizumab: Route of administration:
In this study, the second step of the treatment will be administering intra-arterial bevacizumab into the appropriate cervical artery.
|
|---|---|
|
Overall Study
Adverse Event
|
2
|
Baseline Characteristics
Low-dose Intra-arterial Bevacizumab for Edema and Radiation Necrosis Therapeutic Intervention (LIBERTI)
Baseline characteristics by cohort
| Measure |
Low-dose Intra-arterial Avastin (Bevacizumab)
n=10 Participants
A single intra-arterial dose of 2.5 mg/kg bevacizumab will be administered after osmotic blood-brain-barrier disruption with intra-arterial 25% mannitol at rate of 4-12 ml/sec for 30 seconds.
25% Mannitol: Route of administration: In this study, the first step of the treatment will be performing osmotic blood-brain-barrier disruption with administration of intra-arterial 25% Mannitol into the appropriate cervical artery.
Low-dose Intra-arterial Bevacizumab: Route of administration:
In this study, the second step of the treatment will be administering intra-arterial bevacizumab into the appropriate cervical artery.
|
|---|---|
|
Age, Continuous
|
35.1 years
STANDARD_DEVIATION 14.8 • n=99 Participants
|
|
Sex: Female, Male
Female
|
8 Participants
n=99 Participants
|
|
Sex: Female, Male
Male
|
2 Participants
n=99 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
1 Participants
n=99 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
9 Participants
n=99 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=99 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=99 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=99 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=99 Participants
|
|
Race (NIH/OMB)
Black or African American
|
1 Participants
n=99 Participants
|
|
Race (NIH/OMB)
White
|
9 Participants
n=99 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=99 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=99 Participants
|
|
Region of Enrollment
United States
|
10 participants
n=99 Participants
|
|
MRI of Brain: volume of radiation necrosis
|
14.5 cubic centimeters, or cm^3
STANDARD_DEVIATION 12.1 • n=99 Participants
|
|
MRI of Brain: volume of edema
|
86.8 cubic centimeters, or cm^3
STANDARD_DEVIATION 95.9 • n=99 Participants
|
|
Headache severity via Migraine Disability Assessment (MIDAS) TOTAL SCORE
|
81.7 units on a scale from 0 to 450
STANDARD_DEVIATION 110.1 • n=99 Participants
|
|
DAYS of Headache via Migraine Disability Assessment (MIDAS)
|
33.3 Days of headache over past 3 months
STANDARD_DEVIATION 29.8 • n=99 Participants
|
|
Headache PAIN LEVEL via Migraine Disability Assessment (MIDAS)
|
6.9 units on a scale from 0 to 10
STANDARD_DEVIATION 2.2 • n=99 Participants
|
|
Headache severity via Headache Impact Test (HIT-6)
|
62.4 units on a scale from 36 - 78
STANDARD_DEVIATION 7.5 • n=99 Participants
|
|
Cumulative Days of Steroid use during 12 months Pre-Bevacizumab
|
52.5 Days
n=99 Participants
|
|
Karnofsky Performance Status Scale
|
79.0 % on Karnofsky scale
STANDARD_DEVIATION 9.9 • n=99 Participants
|
|
Digits Forward via Neuropsychological Assessment Battery
|
41.1 T score with Mean=50, SD=10
STANDARD_DEVIATION 11.8 • n=99 Participants
|
|
Digits Backward via Neuropsychological Assessment Battery
|
44.9 T score with Mean=50, SD=10
STANDARD_DEVIATION 8.3 • n=99 Participants
|
|
Numbers and Letters Speed via Neuropsychological Assessment Battery
|
38.2 T score with Mean=50, SD=10
STANDARD_DEVIATION 10.7 • n=99 Participants
|
|
Numbers and Letters Errors via Neuropsychological Assessment Battery
|
44.6 T score with Mean=50, SD=10
STANDARD_DEVIATION 3.8 • n=99 Participants
|
|
Numbers and Letters Efficiency via Neuropsychological Assessment Battery
|
41.0 T score with Mean=50, SD=10
STANDARD_DEVIATION 14.6 • n=99 Participants
|
|
Naming via Neuropsychological Assessment Battery
|
47.6 T score with Mean=50, SD=10
STANDARD_DEVIATION 3.4 • n=99 Participants
|
|
List Learning List Immediate Recall via Neuropsychological Assessment Battery
|
44.6 T score with Mean=50, SD=10
STANDARD_DEVIATION 2.4 • n=99 Participants
|
|
List Learning List Long Delayed Recall via Neuropsychological Assessment Battery
|
44.6 T score with Mean=50, SD=10
STANDARD_DEVIATION 3.5 • n=99 Participants
|
|
Shape Learning Immediate Recognition via Neuropsychological Assessment Battery
|
42.9 T score with Mean=50, SD=10
STANDARD_DEVIATION 3.0 • n=99 Participants
|
|
Shape Learning Delayed Recognition via Neuropsychological Assessment Battery
|
41.3 T score with Mean=50, SD=10
STANDARD_DEVIATION 3.6 • n=99 Participants
|
|
Story Learning Phrase Unit Immediate Recall via Neuropsychological Assessment Battery
|
43.2 T score with Mean=50, SD=10
STANDARD_DEVIATION 2.9 • n=99 Participants
|
|
Story Learning Phrase Unit Delayed Recall via Neuropsychological Assessment Battery
|
43.7 T score with Mean=50, SD=10
STANDARD_DEVIATION 2.3 • n=99 Participants
|
|
Design Construction via Neuropsychological Assessment Battery
|
41.4 T score with Mean=50, SD=10
STANDARD_DEVIATION 3.5 • n=99 Participants
|
|
Mazes via Neuropsychological Assessment Battery
|
39.8 T score with Mean=50, SD=10
STANDARD_DEVIATION 2.9 • n=99 Participants
|
|
Categories via Neuropsychological Assessment Battery
|
41.8 T score with Mean=50, SD=10
STANDARD_DEVIATION 2.2 • n=99 Participants
|
|
Word Generation via Neuropsychological Assessment Battery
|
45.0 T score with Mean=50, SD=10
STANDARD_DEVIATION 3.7 • n=99 Participants
|
|
Full Scale Intelligence Quotient (FSIQ) via Wechsler Test of Adult Reading
|
95.8 units on a scale from 28 to 210
STANDARD_DEVIATION 4.1 • n=99 Participants
|
PRIMARY outcome
Timeframe: Baseline (before treatment), and 3 months and 12 months after single dose intra-arterial Avastin (bevacizumab)Population: 10 adult subjects presented with medically refractory radiation necrosis of the brain and disabling headache. All were treated with steroids prior to study enrollment.
Imaging response to therapy will be quantitatively assessed on MRI using volumetric analysis. Regions of T2 and FLAIR prolongation above contralateral white matter will be calculated and quantified in cubic centimeters. Region of interest (ROI) will be created using a semi-automated, thresholding and region-growing technique. Enhancement of the lesion will be calculated using similar volumetric ROI analysis with a contrast threshold of 40% above background and measured in cubic centimeters.
Outcome measures
| Measure |
Low-dose Intra-arterial Avastin (Bevacizumab)
n=10 Participants
A single intra-arterial dose of 2.5 mg/kg bevacizumab will be administered after osmotic blood-brain-barrier disruption with intra-arterial 25% mannitol at rate of 4-12 ml/sec for 30 seconds.
25% Mannitol: Route of administration: In this study, the first step of the treatment will be performing osmotic blood-brain-barrier disruption with administration of intra-arterial 25% Mannitol into the appropriate cervical artery.
Low-dose Intra-arterial bevacizumab: Route of administration:
In this study, the second step of the treatment will be administering intra-arterial bevacizumab into the appropriate cervical artery.
|
|---|---|
|
Change in Radiation Necrosis and Cerebral Edema After a Single Treatment of Low Dose Intra-arterial Avastin (Bevacizumab)
Vol EDEMA at Baseline
|
86.8 cm^3
Standard Deviation 95.9
|
|
Change in Radiation Necrosis and Cerebral Edema After a Single Treatment of Low Dose Intra-arterial Avastin (Bevacizumab)
Vol EDEMA at 3 months
|
38.6 cm^3
Standard Deviation 37.5
|
|
Change in Radiation Necrosis and Cerebral Edema After a Single Treatment of Low Dose Intra-arterial Avastin (Bevacizumab)
Vol EDEMA at 12 months
|
32.6 cm^3
Standard Deviation 33.7
|
|
Change in Radiation Necrosis and Cerebral Edema After a Single Treatment of Low Dose Intra-arterial Avastin (Bevacizumab)
Vol Radiation Necrosis at Baseline
|
14.5 cm^3
Standard Deviation 12.1
|
|
Change in Radiation Necrosis and Cerebral Edema After a Single Treatment of Low Dose Intra-arterial Avastin (Bevacizumab)
Vol Radiation Necrosis at 3 months
|
6.6 cm^3
Standard Deviation 7.5
|
|
Change in Radiation Necrosis and Cerebral Edema After a Single Treatment of Low Dose Intra-arterial Avastin (Bevacizumab)
Vol Radiation Necrosis at 12 months
|
3.2 cm^3
Standard Deviation 3.3
|
SECONDARY outcome
Timeframe: Baseline (before treatment), and 6 weeks, 3 months, 6 months, 9 months, and 12 months after single dose intra-arterial Avastin (bevacizumab)Population: 10 adult subjects presented with medically refractory radiation necrosis of the brain and disabling headache.
We will determine how severely headache affect the patient's life before and after treatment by performing the Migraine Disability Assessment (MIDAS) questionnaire. MIDAS TOTAL SCORE is the sum of Items 1 through 5. A Total Score of 0-5 signifies little or no disability, score of 6-10 signifies mild disability, score of 11-20 signifies moderate disability, and score of 21+ signifies severe disability. The theoretical maximum score would be 450.
Outcome measures
| Measure |
Low-dose Intra-arterial Avastin (Bevacizumab)
n=10 Participants
A single intra-arterial dose of 2.5 mg/kg bevacizumab will be administered after osmotic blood-brain-barrier disruption with intra-arterial 25% mannitol at rate of 4-12 ml/sec for 30 seconds.
25% Mannitol: Route of administration: In this study, the first step of the treatment will be performing osmotic blood-brain-barrier disruption with administration of intra-arterial 25% Mannitol into the appropriate cervical artery.
Low-dose Intra-arterial bevacizumab: Route of administration:
In this study, the second step of the treatment will be administering intra-arterial bevacizumab into the appropriate cervical artery.
|
|---|---|
|
Change in Headache Associated Morbidity Measured With MIDAS TOTAL SCORE After a Single Treatment of Low Dose Intra-arterial Avastin (Bevacizumab) Will be Measured.
MIDAS TOTAL at Baseline
|
81.7 score on a scale
Standard Deviation 110.1
|
|
Change in Headache Associated Morbidity Measured With MIDAS TOTAL SCORE After a Single Treatment of Low Dose Intra-arterial Avastin (Bevacizumab) Will be Measured.
MIDAS TOTAL at 6 weeks
|
49.7 score on a scale
Standard Deviation 66.6
|
|
Change in Headache Associated Morbidity Measured With MIDAS TOTAL SCORE After a Single Treatment of Low Dose Intra-arterial Avastin (Bevacizumab) Will be Measured.
MIDAS TOTAL at 3 months
|
22.1 score on a scale
Standard Deviation 30.3
|
|
Change in Headache Associated Morbidity Measured With MIDAS TOTAL SCORE After a Single Treatment of Low Dose Intra-arterial Avastin (Bevacizumab) Will be Measured.
MIDAS TOTAL at 6 months
|
28.3 score on a scale
Standard Deviation 46.2
|
|
Change in Headache Associated Morbidity Measured With MIDAS TOTAL SCORE After a Single Treatment of Low Dose Intra-arterial Avastin (Bevacizumab) Will be Measured.
MIDAS TOTAL at 9 months
|
24.4 score on a scale
Standard Deviation 33.7
|
|
Change in Headache Associated Morbidity Measured With MIDAS TOTAL SCORE After a Single Treatment of Low Dose Intra-arterial Avastin (Bevacizumab) Will be Measured.
MIDAS TOTAL at 12 months
|
15.6 score on a scale
Standard Deviation 26.5
|
SECONDARY outcome
Timeframe: Baseline (before treatment), and 6 weeks, 3 months, 6 months, 9 months, and 12 months after single dose intra-arterial Avastin (bevacizumab)Population: 10 adult subjects presented with medically refractory radiation necrosis of the brain and disabling headache.
We will determine how severely headache affect the patient's life before and after treatment by performing the Migraine Disability Assessment (MIDAS) questionnaire. MIDAS DAYS of HEADACHE is Item 6 of the questionnaire which sums total number of days the patient had headache symptoms over the past 3 months regardless of headache severity or resultant disability. Min score of 0 days is the best possible score. Max Score of 90 days is worse possible score, meaning the patient experienced headache pain every day over past 3 months.
Outcome measures
| Measure |
Low-dose Intra-arterial Avastin (Bevacizumab)
n=10 Participants
A single intra-arterial dose of 2.5 mg/kg bevacizumab will be administered after osmotic blood-brain-barrier disruption with intra-arterial 25% mannitol at rate of 4-12 ml/sec for 30 seconds.
25% Mannitol: Route of administration: In this study, the first step of the treatment will be performing osmotic blood-brain-barrier disruption with administration of intra-arterial 25% Mannitol into the appropriate cervical artery.
Low-dose Intra-arterial bevacizumab: Route of administration:
In this study, the second step of the treatment will be administering intra-arterial bevacizumab into the appropriate cervical artery.
|
|---|---|
|
Change in Headache Associated Morbidity Measured With MIDAS DAYS of HEADACHE After a Single Treatment of Low Dose Intra-arterial Avastin (Bevacizumab) Will be Measured.
MIDAS DAYS of HEADACHE at Baseline
|
33.3 Days
Standard Deviation 29.8
|
|
Change in Headache Associated Morbidity Measured With MIDAS DAYS of HEADACHE After a Single Treatment of Low Dose Intra-arterial Avastin (Bevacizumab) Will be Measured.
MIDAS DAYS of HEADACHE at 6 weeks
|
25.8 Days
Standard Deviation 35.0
|
|
Change in Headache Associated Morbidity Measured With MIDAS DAYS of HEADACHE After a Single Treatment of Low Dose Intra-arterial Avastin (Bevacizumab) Will be Measured.
MIDAS DAYS of HEADACHE at 3 months
|
9.0 Days
Standard Deviation 9.3
|
|
Change in Headache Associated Morbidity Measured With MIDAS DAYS of HEADACHE After a Single Treatment of Low Dose Intra-arterial Avastin (Bevacizumab) Will be Measured.
MIDAS DAYS of HEADACHE at 6 months
|
14.6 Days
Standard Deviation 14.1
|
|
Change in Headache Associated Morbidity Measured With MIDAS DAYS of HEADACHE After a Single Treatment of Low Dose Intra-arterial Avastin (Bevacizumab) Will be Measured.
MIDAS DAYS of HEADACHE at 9 months
|
12.4 Days
Standard Deviation 17.6
|
|
Change in Headache Associated Morbidity Measured With MIDAS DAYS of HEADACHE After a Single Treatment of Low Dose Intra-arterial Avastin (Bevacizumab) Will be Measured.
MIDAS DAYS of HEADACHE at 12 months
|
11.5 Days
Standard Deviation 17.0
|
SECONDARY outcome
Timeframe: Baseline (before treatment), and 6 weeks, 3 months, 6 months, 9 months, and 12 months after single dose intra-arterial Avastin (bevacizumab)Population: 10 adult subjects presented with medically refractory radiation necrosis of the brain and disabling headache.
We will determine how severely headache affect the patient's life before and after treatment by performing the Migraine Disability Assessment (MIDAS) questionnaire. MIDAS PAIN LEVEL is Item 7 which rates the 3-month average headache PAIN LEVEL on scale from 0 to 10 where 0 = no pain at all, and 10 = pain as bad as it can be.
Outcome measures
| Measure |
Low-dose Intra-arterial Avastin (Bevacizumab)
n=10 Participants
A single intra-arterial dose of 2.5 mg/kg bevacizumab will be administered after osmotic blood-brain-barrier disruption with intra-arterial 25% mannitol at rate of 4-12 ml/sec for 30 seconds.
25% Mannitol: Route of administration: In this study, the first step of the treatment will be performing osmotic blood-brain-barrier disruption with administration of intra-arterial 25% Mannitol into the appropriate cervical artery.
Low-dose Intra-arterial bevacizumab: Route of administration:
In this study, the second step of the treatment will be administering intra-arterial bevacizumab into the appropriate cervical artery.
|
|---|---|
|
Change in Headache Associated Morbidity Measured With MIDAS PAIN LEVEL After a Single Treatment of Low Dose Intra-arterial Avastin (Bevacizumab) Will be Measured.
MIDAS PAIN LEVEL at Baseline
|
6.9 score on a scale
Standard Deviation 2.2
|
|
Change in Headache Associated Morbidity Measured With MIDAS PAIN LEVEL After a Single Treatment of Low Dose Intra-arterial Avastin (Bevacizumab) Will be Measured.
MIDAS PAIN LEVEL at 6 weeks
|
6.4 score on a scale
Standard Deviation 1.8
|
|
Change in Headache Associated Morbidity Measured With MIDAS PAIN LEVEL After a Single Treatment of Low Dose Intra-arterial Avastin (Bevacizumab) Will be Measured.
MIDAS PAIN LEVEL at 3 months
|
4.7 score on a scale
Standard Deviation 2.9
|
|
Change in Headache Associated Morbidity Measured With MIDAS PAIN LEVEL After a Single Treatment of Low Dose Intra-arterial Avastin (Bevacizumab) Will be Measured.
MIDAS PAIN LEVEL at 6 months
|
5.0 score on a scale
Standard Deviation 2.9
|
|
Change in Headache Associated Morbidity Measured With MIDAS PAIN LEVEL After a Single Treatment of Low Dose Intra-arterial Avastin (Bevacizumab) Will be Measured.
MIDAS PAIN LEVEL at 9 months
|
4.8 score on a scale
Standard Deviation 3.0
|
|
Change in Headache Associated Morbidity Measured With MIDAS PAIN LEVEL After a Single Treatment of Low Dose Intra-arterial Avastin (Bevacizumab) Will be Measured.
MIDAS PAIN LEVEL at 12 months
|
4.8 score on a scale
Standard Deviation 3.5
|
SECONDARY outcome
Timeframe: Baseline (before treatment), and 6 weeks, 3 months, 6 months, 9 months, and 12 months after single dose intra-arterial Avastin (bevacizumab)Population: 10 adult subjects presented with medically refractory radiation necrosis of the brain and disabling headache. All 10 received single treatment of low dose intra-arterial bevacizumab.
Quantitative change in headache will be assessed by performing the Headache Impact Test (HIT-6), which is a fixed-length 6-item questionnaire. The score for this questionnaire can range from 36 to 78, with 36 indicating minimum headache impact and the max score of 78 indicating worst possible headache impact.
Outcome measures
| Measure |
Low-dose Intra-arterial Avastin (Bevacizumab)
n=10 Participants
A single intra-arterial dose of 2.5 mg/kg bevacizumab will be administered after osmotic blood-brain-barrier disruption with intra-arterial 25% mannitol at rate of 4-12 ml/sec for 30 seconds.
25% Mannitol: Route of administration: In this study, the first step of the treatment will be performing osmotic blood-brain-barrier disruption with administration of intra-arterial 25% Mannitol into the appropriate cervical artery.
Low-dose Intra-arterial bevacizumab: Route of administration:
In this study, the second step of the treatment will be administering intra-arterial bevacizumab into the appropriate cervical artery.
|
|---|---|
|
Change in Headache Measured With Headache Impact Test (HIT-6) After a Single Treatment of Low Dose Intra-arterial Avastin (Bevacizumab)
Headache Impact Test-6, Baseline
|
62.4 score on a scale
Standard Deviation 7.5
|
|
Change in Headache Measured With Headache Impact Test (HIT-6) After a Single Treatment of Low Dose Intra-arterial Avastin (Bevacizumab)
Headache Impact Test-6, 6 Weeks
|
54.5 score on a scale
Standard Deviation 11.4
|
|
Change in Headache Measured With Headache Impact Test (HIT-6) After a Single Treatment of Low Dose Intra-arterial Avastin (Bevacizumab)
Headache Impact Test-6, 3 months
|
52.3 score on a scale
Standard Deviation 13.0
|
|
Change in Headache Measured With Headache Impact Test (HIT-6) After a Single Treatment of Low Dose Intra-arterial Avastin (Bevacizumab)
Headache Impact Test-6, 6 months
|
53.3 score on a scale
Standard Deviation 13.6
|
|
Change in Headache Measured With Headache Impact Test (HIT-6) After a Single Treatment of Low Dose Intra-arterial Avastin (Bevacizumab)
Headache Impact Test-6, 9 months
|
53.2 score on a scale
Standard Deviation 15.4
|
|
Change in Headache Measured With Headache Impact Test (HIT-6) After a Single Treatment of Low Dose Intra-arterial Avastin (Bevacizumab)
Headache Impact Test-6, 12 months
|
52.1 score on a scale
Standard Deviation 14.4
|
SECONDARY outcome
Timeframe: Baseline (before treatment), Day 1, and at 3 months, and 12 months after single dose intra-arterial Avastin (bevacizumab)Population: 10 adult subjects presented with medically refractory radiation necrosis of the brain and disabling headache. All were treated with steroids prior to study enrollment.
Quantitative change in functional status will be assessed by performing Karnofsky Performance Status Scale (KPS). The KPS score can range from 0 to 100 where 0 is dead and 100 is fully alive and normal with no complaints and no evidence of disease.
Outcome measures
| Measure |
Low-dose Intra-arterial Avastin (Bevacizumab)
n=10 Participants
A single intra-arterial dose of 2.5 mg/kg bevacizumab will be administered after osmotic blood-brain-barrier disruption with intra-arterial 25% mannitol at rate of 4-12 ml/sec for 30 seconds.
25% Mannitol: Route of administration: In this study, the first step of the treatment will be performing osmotic blood-brain-barrier disruption with administration of intra-arterial 25% Mannitol into the appropriate cervical artery.
Low-dose Intra-arterial bevacizumab: Route of administration:
In this study, the second step of the treatment will be administering intra-arterial bevacizumab into the appropriate cervical artery.
|
|---|---|
|
Change in Functional Status After a Single Treatment of Low Dose Intra-arterial Bevacizumab
Karnofsky at Baseline
|
79.0 units on a scale
Standard Deviation 9.9
|
|
Change in Functional Status After a Single Treatment of Low Dose Intra-arterial Bevacizumab
Karnofsky at Day 1
|
81.0 units on a scale
Standard Deviation 7.4
|
|
Change in Functional Status After a Single Treatment of Low Dose Intra-arterial Bevacizumab
Karnofsky at Month 3
|
83.0 units on a scale
Standard Deviation 11.6
|
|
Change in Functional Status After a Single Treatment of Low Dose Intra-arterial Bevacizumab
Karnofsky at Month 12
|
86.3 units on a scale
Standard Deviation 7.4
|
SECONDARY outcome
Timeframe: 12 months prior to single dose of IA bevacizumab; 12 months following single dose of IA bevacizumabPopulation: 10 adult patients age 31.0 (IQR 24.3, 42.8) years, including 8 (80%) women, 2 (20%) men, 9 (90%) white, 1 (10%) black, 9 (90%) Non-Hispanic, and 1 (10%) Hispanic
To assess the utility of intra-arterial (IA) bevacizumab treatment in allowing decreased steroid usage, total cumulative days of steroid usage were compared between the 12 months PRIOR TO and the 12 months IMMEDIATELY FOLLOWING IA bevacizumab. Days of steroid usage were tabulated via medical history and chart review at the baseline visit for the 12 months prior to IA bevacizumab and post-treatment on days 0 and 1, week 6, and months 3, 6, 9 and 12 for the 12 month total after IA bevacizumab treatment. Excluding topical steroid preparations, all days of enteral or parenteral steroid intake of any dose were included in the cumulative summation.
Outcome measures
| Measure |
Low-dose Intra-arterial Avastin (Bevacizumab)
n=10 Participants
A single intra-arterial dose of 2.5 mg/kg bevacizumab will be administered after osmotic blood-brain-barrier disruption with intra-arterial 25% mannitol at rate of 4-12 ml/sec for 30 seconds.
25% Mannitol: Route of administration: In this study, the first step of the treatment will be performing osmotic blood-brain-barrier disruption with administration of intra-arterial 25% Mannitol into the appropriate cervical artery.
Low-dose Intra-arterial bevacizumab: Route of administration:
In this study, the second step of the treatment will be administering intra-arterial bevacizumab into the appropriate cervical artery.
|
|---|---|
|
Change in Steroid Usage After a Single Treatment of Low Dose Intra-arterial Avastin (Bevacizumab)
12 months PRIOR to IA bevacizumab
|
61.5 Days
Interval 0.0 to 156.25
|
|
Change in Steroid Usage After a Single Treatment of Low Dose Intra-arterial Avastin (Bevacizumab)
12 months AFTER IA bevacizumab
|
13.0 Days
Interval 0.0 to 87.25
|
SECONDARY outcome
Timeframe: Baseline (before bevacizumab), and 3 months and 12 months after single dose intra-arterial Avastin (bevacizumab)Population: 10 adult subjects, 2 male and 8 female, 1 black and 9 white, 1 Hispanic and 9 non-Hispanic, recruited from outpatient medical clinics at 2 academic medical centers (5 subjects per center) between Nov 2016 and Jan 2018. 2 subjects experienced progression of radiation necrosis requiring intervention at approx. month 11. Their 12-month data are not included in the Neurocognitive reporting.
In order to investigate post-operative changes in Neurocognitive performance after intra-arterial bevacizumab, patients who consented underwent formal neuropsychological battery testing. Sixteen subtests from the Neuropsychological Assessment Battery (Stern \& White, PAR Inc.) were chosen for brevity, sensitivity, and due to the wide range of available normative data (ages 18-97). For each subtest, T-score = 50 is the normative mean with SD = 10. Thus T-scores of 40-60 are within one standard deviation of the mean and are considered generally normal. Scores increasingly below 40 indicate decreased neurocognitive performance compared to healthy demographically matched persons. Scores significantly above 60 indicate increase neurocognitive performance compared to healthy demographically matched persons.
Outcome measures
| Measure |
Low-dose Intra-arterial Avastin (Bevacizumab)
n=10 Participants
A single intra-arterial dose of 2.5 mg/kg bevacizumab will be administered after osmotic blood-brain-barrier disruption with intra-arterial 25% mannitol at rate of 4-12 ml/sec for 30 seconds.
25% Mannitol: Route of administration: In this study, the first step of the treatment will be performing osmotic blood-brain-barrier disruption with administration of intra-arterial 25% Mannitol into the appropriate cervical artery.
Low-dose Intra-arterial bevacizumab: Route of administration:
In this study, the second step of the treatment will be administering intra-arterial bevacizumab into the appropriate cervical artery.
|
|---|---|
|
Post-operative Neurocognitive Change After Intra-arterial Bevacizumab
Story Learning Phrase Unit Immediate Recall at BASELINE
|
43.2 T score where mean T=50, SD=10
Standard Deviation 9.2
|
|
Post-operative Neurocognitive Change After Intra-arterial Bevacizumab
Story Learning Phrase Unit Immediate Recall at 3 months
|
47.1 T score where mean T=50, SD=10
Standard Deviation 12.7
|
|
Post-operative Neurocognitive Change After Intra-arterial Bevacizumab
Story Learning Phrase Unit Immediate Recall at 12 months
|
49.6 T score where mean T=50, SD=10
Standard Deviation 12.8
|
|
Post-operative Neurocognitive Change After Intra-arterial Bevacizumab
Story Learning Phrase Unit Delayed Recall at BASELINE
|
43.7 T score where mean T=50, SD=10
Standard Deviation 7.3
|
|
Post-operative Neurocognitive Change After Intra-arterial Bevacizumab
Digits Forward at Baseline
|
41.1 T score where mean T=50, SD=10
Standard Deviation 11.8
|
|
Post-operative Neurocognitive Change After Intra-arterial Bevacizumab
Digits Forward at 3 months
|
44.1 T score where mean T=50, SD=10
Standard Deviation 12.2
|
|
Post-operative Neurocognitive Change After Intra-arterial Bevacizumab
Digits Forward at 12 months
|
42.3 T score where mean T=50, SD=10
Standard Deviation 11.7
|
|
Post-operative Neurocognitive Change After Intra-arterial Bevacizumab
Digits Backward at Baseline
|
44.9 T score where mean T=50, SD=10
Standard Deviation 8.3
|
|
Post-operative Neurocognitive Change After Intra-arterial Bevacizumab
Digits Backward at 3 months
|
44.9 T score where mean T=50, SD=10
Standard Deviation 11.9
|
|
Post-operative Neurocognitive Change After Intra-arterial Bevacizumab
Digits Backward at 12 months
|
40.3 T score where mean T=50, SD=10
Standard Deviation 13.1
|
|
Post-operative Neurocognitive Change After Intra-arterial Bevacizumab
Numbers & Letters SPEED at Baseline
|
38.2 T score where mean T=50, SD=10
Standard Deviation 10.7
|
|
Post-operative Neurocognitive Change After Intra-arterial Bevacizumab
Numbers & Letters SPEED at 3 months
|
36.7 T score where mean T=50, SD=10
Standard Deviation 10.8
|
|
Post-operative Neurocognitive Change After Intra-arterial Bevacizumab
Numbers & Letters SPEED at 12 months
|
36.8 T score where mean T=50, SD=10
Standard Deviation 10.7
|
|
Post-operative Neurocognitive Change After Intra-arterial Bevacizumab
Numbers & Letters Errors at BASELINE
|
44.6 T score where mean T=50, SD=10
Standard Deviation 12.0
|
|
Post-operative Neurocognitive Change After Intra-arterial Bevacizumab
Numbers & Letters Errors at 3 months
|
47.4 T score where mean T=50, SD=10
Standard Deviation 12.6
|
|
Post-operative Neurocognitive Change After Intra-arterial Bevacizumab
Numbers & Letters Errors at 12 months
|
52.9 T score where mean T=50, SD=10
Standard Deviation 10.1
|
|
Post-operative Neurocognitive Change After Intra-arterial Bevacizumab
Numbers & Letters EFFICIENCY at Baseline
|
41.0 T score where mean T=50, SD=10
Standard Deviation 14.6
|
|
Post-operative Neurocognitive Change After Intra-arterial Bevacizumab
Numbers & Letters EFFICIENCY at 3 Months
|
36.6 T score where mean T=50, SD=10
Standard Deviation 11.8
|
|
Post-operative Neurocognitive Change After Intra-arterial Bevacizumab
Numbers & Letters EFFICIENCY at 12 months
|
36.6 T score where mean T=50, SD=10
Standard Deviation 11.1
|
|
Post-operative Neurocognitive Change After Intra-arterial Bevacizumab
Naming at BASELINE
|
47.6 T score where mean T=50, SD=10
Standard Deviation 10.6
|
|
Post-operative Neurocognitive Change After Intra-arterial Bevacizumab
Naming at 3 months
|
49.9 T score where mean T=50, SD=10
Standard Deviation 7.3
|
|
Post-operative Neurocognitive Change After Intra-arterial Bevacizumab
Naming at 12 months
|
49.1 T score where mean T=50, SD=10
Standard Deviation 10.9
|
|
Post-operative Neurocognitive Change After Intra-arterial Bevacizumab
List Learning List Immediate Recall at BASELINE
|
44.6 T score where mean T=50, SD=10
Standard Deviation 7.7
|
|
Post-operative Neurocognitive Change After Intra-arterial Bevacizumab
List Learning List Immediate Recall at 3 months
|
44.2 T score where mean T=50, SD=10
Standard Deviation 13.1
|
|
Post-operative Neurocognitive Change After Intra-arterial Bevacizumab
List Learning List Immediate Recall at 12 months
|
46.4 T score where mean T=50, SD=10
Standard Deviation 7.8
|
|
Post-operative Neurocognitive Change After Intra-arterial Bevacizumab
List Learning List Long Delayed Recall at BASELINE
|
44.6 T score where mean T=50, SD=10
Standard Deviation 11.1
|
|
Post-operative Neurocognitive Change After Intra-arterial Bevacizumab
List Learning List Long Delayed Recall at 3 months
|
42.6 T score where mean T=50, SD=10
Standard Deviation 11.0
|
|
Post-operative Neurocognitive Change After Intra-arterial Bevacizumab
List Learning List Long Delayed Recall at 12 months
|
51.3 T score where mean T=50, SD=10
Standard Deviation 12.1
|
|
Post-operative Neurocognitive Change After Intra-arterial Bevacizumab
Shape Learning Immediate Recognition at BASELINE
|
42.9 T score where mean T=50, SD=10
Standard Deviation 9.5
|
|
Post-operative Neurocognitive Change After Intra-arterial Bevacizumab
Shape Learning Immediate Recognition at 3 months
|
48.6 T score where mean T=50, SD=10
Standard Deviation 10.7
|
|
Post-operative Neurocognitive Change After Intra-arterial Bevacizumab
Shape Learning Immediate Recognition at 12 months
|
50.0 T score where mean T=50, SD=10
Standard Deviation 11.3
|
|
Post-operative Neurocognitive Change After Intra-arterial Bevacizumab
Shape Learning Delayed Recognition at BASELINE
|
41.3 T score where mean T=50, SD=10
Standard Deviation 11.3
|
|
Post-operative Neurocognitive Change After Intra-arterial Bevacizumab
Shape Learning Delayed Recognition at 3 months
|
46.0 T score where mean T=50, SD=10
Standard Deviation 12.2
|
|
Post-operative Neurocognitive Change After Intra-arterial Bevacizumab
Shape Learning Delayed Recognition at 12 months
|
47.3 T score where mean T=50, SD=10
Standard Deviation 9.1
|
|
Post-operative Neurocognitive Change After Intra-arterial Bevacizumab
Story Learning Phrase Unit Delayed Recall at 3 months
|
48.5 T score where mean T=50, SD=10
Standard Deviation 9.2
|
|
Post-operative Neurocognitive Change After Intra-arterial Bevacizumab
Story Learning Phrase Unit Delayed Recall at 12 months
|
47.1 T score where mean T=50, SD=10
Standard Deviation 8.0
|
|
Post-operative Neurocognitive Change After Intra-arterial Bevacizumab
Design Construction at BASELINE
|
41.4 T score where mean T=50, SD=10
Standard Deviation 11.1
|
|
Post-operative Neurocognitive Change After Intra-arterial Bevacizumab
Design Construction at 3 months
|
41.6 T score where mean T=50, SD=10
Standard Deviation 14.3
|
|
Post-operative Neurocognitive Change After Intra-arterial Bevacizumab
Design Construction at 12 months
|
45.8 T score where mean T=50, SD=10
Standard Deviation 9.6
|
|
Post-operative Neurocognitive Change After Intra-arterial Bevacizumab
Mazes at BASELINE
|
39.8 T score where mean T=50, SD=10
Standard Deviation 9.2
|
|
Post-operative Neurocognitive Change After Intra-arterial Bevacizumab
Mazes at 3 months
|
43.3 T score where mean T=50, SD=10
Standard Deviation 12.3
|
|
Post-operative Neurocognitive Change After Intra-arterial Bevacizumab
Mazes at 12 months
|
43.0 T score where mean T=50, SD=10
Standard Deviation 11.7
|
|
Post-operative Neurocognitive Change After Intra-arterial Bevacizumab
Categories at BASELINE
|
41.8 T score where mean T=50, SD=10
Standard Deviation 6.8
|
|
Post-operative Neurocognitive Change After Intra-arterial Bevacizumab
Categories at 3 months
|
44.5 T score where mean T=50, SD=10
Standard Deviation 10.4
|
|
Post-operative Neurocognitive Change After Intra-arterial Bevacizumab
Categories at 12 months
|
39.9 T score where mean T=50, SD=10
Standard Deviation 8.2
|
|
Post-operative Neurocognitive Change After Intra-arterial Bevacizumab
Word Generation at BASELINE
|
45.0 T score where mean T=50, SD=10
Standard Deviation 11.8
|
|
Post-operative Neurocognitive Change After Intra-arterial Bevacizumab
Word Generation at 3 months
|
45.6 T score where mean T=50, SD=10
Standard Deviation 9.8
|
|
Post-operative Neurocognitive Change After Intra-arterial Bevacizumab
Word Generation at 12 months
|
49.0 T score where mean T=50, SD=10
Standard Deviation 11.3
|
Adverse Events
Low-dose Intra-arterial Bevacizumab
Serious events: 6 serious events
Other events: 9 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Low-dose Intra-arterial Bevacizumab
n=10 participants at risk
A single intra-arterial dose of 2.5 mg/kg bevacizumab will be administered after osmotic blood-brain-barrier disruption with intra-arterial 25% mannitol at rate of 4-12 ml/sec for 30 seconds.
25% Mannitol: Route of administration: In this study, the first step of the treatment will be performing osmotic blood-brain-barrier disruption with administration of intra-arterial 25% Mannitol into the appropriate cervical artery.
Low-dose Intra-arterial Bevacizumab: Route of administration:
In this study, the second step of the treatment will be administering intra-arterial bevacizumab into the appropriate cervical artery.
|
|---|---|
|
Nervous system disorders
Seizure
|
20.0%
2/10 • Number of events 2 • 1 year
Adverse Event Monitoring performed on Day 0, Day 1, Week 6, Month 3, and Month 12
|
|
Nervous system disorders
Acute encephalopathy
|
10.0%
1/10 • Number of events 1 • 1 year
Adverse Event Monitoring performed on Day 0, Day 1, Week 6, Month 3, and Month 12
|
|
Nervous system disorders
Double Vision
|
10.0%
1/10 • Number of events 1 • 1 year
Adverse Event Monitoring performed on Day 0, Day 1, Week 6, Month 3, and Month 12
|
|
Cardiac disorders
Chest Pain
|
10.0%
1/10 • Number of events 1 • 1 year
Adverse Event Monitoring performed on Day 0, Day 1, Week 6, Month 3, and Month 12
|
|
Nervous system disorders
Headache
|
10.0%
1/10 • Number of events 1 • 1 year
Adverse Event Monitoring performed on Day 0, Day 1, Week 6, Month 3, and Month 12
|
|
Nervous system disorders
Dizziness
|
10.0%
1/10 • Number of events 1 • 1 year
Adverse Event Monitoring performed on Day 0, Day 1, Week 6, Month 3, and Month 12
|
|
Nervous system disorders
Dysarthria
|
10.0%
1/10 • Number of events 1 • 1 year
Adverse Event Monitoring performed on Day 0, Day 1, Week 6, Month 3, and Month 12
|
|
Nervous system disorders
Left Lower Extremity Hemiparesis
|
10.0%
1/10 • Number of events 1 • 1 year
Adverse Event Monitoring performed on Day 0, Day 1, Week 6, Month 3, and Month 12
|
|
Nervous system disorders
Left Upper Extremity Hemiparesis
|
10.0%
1/10 • Number of events 1 • 1 year
Adverse Event Monitoring performed on Day 0, Day 1, Week 6, Month 3, and Month 12
|
|
Nervous system disorders
Cerebral Edema
|
10.0%
1/10 • Number of events 1 • 1 year
Adverse Event Monitoring performed on Day 0, Day 1, Week 6, Month 3, and Month 12
|
Other adverse events
| Measure |
Low-dose Intra-arterial Bevacizumab
n=10 participants at risk
A single intra-arterial dose of 2.5 mg/kg bevacizumab will be administered after osmotic blood-brain-barrier disruption with intra-arterial 25% mannitol at rate of 4-12 ml/sec for 30 seconds.
25% Mannitol: Route of administration: In this study, the first step of the treatment will be performing osmotic blood-brain-barrier disruption with administration of intra-arterial 25% Mannitol into the appropriate cervical artery.
Low-dose Intra-arterial Bevacizumab: Route of administration:
In this study, the second step of the treatment will be administering intra-arterial bevacizumab into the appropriate cervical artery.
|
|---|---|
|
Cardiac disorders
1st degree AV block
|
10.0%
1/10 • Number of events 1 • 1 year
Adverse Event Monitoring performed on Day 0, Day 1, Week 6, Month 3, and Month 12
|
|
Skin and subcutaneous tissue disorders
Acne
|
10.0%
1/10 • Number of events 1 • 1 year
Adverse Event Monitoring performed on Day 0, Day 1, Week 6, Month 3, and Month 12
|
|
Nervous system disorders
Altered Mental Status
|
10.0%
1/10 • Number of events 1 • 1 year
Adverse Event Monitoring performed on Day 0, Day 1, Week 6, Month 3, and Month 12
|
|
Nervous system disorders
Amnesia
|
10.0%
1/10 • Number of events 1 • 1 year
Adverse Event Monitoring performed on Day 0, Day 1, Week 6, Month 3, and Month 12
|
|
Nervous system disorders
Anxiety
|
10.0%
1/10 • Number of events 1 • 1 year
Adverse Event Monitoring performed on Day 0, Day 1, Week 6, Month 3, and Month 12
|
|
Respiratory, thoracic and mediastinal disorders
Asthma episode
|
10.0%
1/10 • Number of events 1 • 1 year
Adverse Event Monitoring performed on Day 0, Day 1, Week 6, Month 3, and Month 12
|
|
Vascular disorders
Bilateral lower leg edema
|
10.0%
1/10 • Number of events 1 • 1 year
Adverse Event Monitoring performed on Day 0, Day 1, Week 6, Month 3, and Month 12
|
|
Eye disorders
Blurred vision
|
40.0%
4/10 • Number of events 6 • 1 year
Adverse Event Monitoring performed on Day 0, Day 1, Week 6, Month 3, and Month 12
|
|
Musculoskeletal and connective tissue disorders
Cervical strain
|
10.0%
1/10 • Number of events 1 • 1 year
Adverse Event Monitoring performed on Day 0, Day 1, Week 6, Month 3, and Month 12
|
|
Nervous system disorders
Confusion
|
10.0%
1/10 • Number of events 2 • 1 year
Adverse Event Monitoring performed on Day 0, Day 1, Week 6, Month 3, and Month 12
|
|
Gastrointestinal disorders
Decreased appetite
|
10.0%
1/10 • Number of events 1 • 1 year
Adverse Event Monitoring performed on Day 0, Day 1, Week 6, Month 3, and Month 12
|
|
General disorders
Dehydration
|
10.0%
1/10 • Number of events 1 • 1 year
Adverse Event Monitoring performed on Day 0, Day 1, Week 6, Month 3, and Month 12
|
|
Eye disorders
Diplopia
|
10.0%
1/10 • Number of events 1 • 1 year
Adverse Event Monitoring performed on Day 0, Day 1, Week 6, Month 3, and Month 12
|
|
Nervous system disorders
Expressive aphasia
|
10.0%
1/10 • Number of events 1 • 1 year
Adverse Event Monitoring performed on Day 0, Day 1, Week 6, Month 3, and Month 12
|
|
General disorders
Fall
|
20.0%
2/10 • Number of events 2 • 1 year
Adverse Event Monitoring performed on Day 0, Day 1, Week 6, Month 3, and Month 12
|
|
Injury, poisoning and procedural complications
Fracture Left Hand
|
10.0%
1/10 • Number of events 1 • 1 year
Adverse Event Monitoring performed on Day 0, Day 1, Week 6, Month 3, and Month 12
|
|
Nervous system disorders
Headache
|
50.0%
5/10 • Number of events 7 • 1 year
Adverse Event Monitoring performed on Day 0, Day 1, Week 6, Month 3, and Month 12
|
|
Psychiatric disorders
Generalized Anxiety
|
10.0%
1/10 • Number of events 1 • 1 year
Adverse Event Monitoring performed on Day 0, Day 1, Week 6, Month 3, and Month 12
|
|
General disorders
Generalized Malaise
|
10.0%
1/10 • Number of events 1 • 1 year
Adverse Event Monitoring performed on Day 0, Day 1, Week 6, Month 3, and Month 12
|
|
Skin and subcutaneous tissue disorders
hair loss
|
10.0%
1/10 • Number of events 1 • 1 year
Adverse Event Monitoring performed on Day 0, Day 1, Week 6, Month 3, and Month 12
|
|
Psychiatric disorders
Hallucinations
|
10.0%
1/10 • Number of events 1 • 1 year
Adverse Event Monitoring performed on Day 0, Day 1, Week 6, Month 3, and Month 12
|
|
Injury, poisoning and procedural complications
Head Trauma
|
10.0%
1/10 • Number of events 1 • 1 year
Adverse Event Monitoring performed on Day 0, Day 1, Week 6, Month 3, and Month 12
|
|
General disorders
Hypercholesterolemia
|
10.0%
1/10 • Number of events 1 • 1 year
Adverse Event Monitoring performed on Day 0, Day 1, Week 6, Month 3, and Month 12
|
|
Nervous system disorders
Hypersomnia
|
10.0%
1/10 • Number of events 1 • 1 year
Adverse Event Monitoring performed on Day 0, Day 1, Week 6, Month 3, and Month 12
|
|
Cardiac disorders
Hypertension
|
10.0%
1/10 • Number of events 1 • 1 year
Adverse Event Monitoring performed on Day 0, Day 1, Week 6, Month 3, and Month 12
|
|
General disorders
Hypertriglyceridemia
|
10.0%
1/10 • Number of events 1 • 1 year
Adverse Event Monitoring performed on Day 0, Day 1, Week 6, Month 3, and Month 12
|
|
Eye disorders
Inability to focus
|
10.0%
1/10 • Number of events 1 • 1 year
Adverse Event Monitoring performed on Day 0, Day 1, Week 6, Month 3, and Month 12
|
|
Nervous system disorders
Inability to focus attention
|
10.0%
1/10 • Number of events 1 • 1 year
Adverse Event Monitoring performed on Day 0, Day 1, Week 6, Month 3, and Month 12
|
|
Pregnancy, puerperium and perinatal conditions
Incomplete Spontaneous Abortion
|
10.0%
1/10 • Number of events 1 • 1 year
Adverse Event Monitoring performed on Day 0, Day 1, Week 6, Month 3, and Month 12
|
|
Nervous system disorders
Dizziness
|
10.0%
1/10 • Number of events 1 • 1 year
Adverse Event Monitoring performed on Day 0, Day 1, Week 6, Month 3, and Month 12
|
|
Eye disorders
Eye twitches
|
10.0%
1/10 • Number of events 1 • 1 year
Adverse Event Monitoring performed on Day 0, Day 1, Week 6, Month 3, and Month 12
|
|
Eye disorders
Homonymous Hemianopia
|
10.0%
1/10 • Number of events 1 • 1 year
Adverse Event Monitoring performed on Day 0, Day 1, Week 6, Month 3, and Month 12
|
|
Skin and subcutaneous tissue disorders
Leg skin tear non-healing wound
|
10.0%
1/10 • Number of events 1 • 1 year
Adverse Event Monitoring performed on Day 0, Day 1, Week 6, Month 3, and Month 12
|
|
Injury, poisoning and procedural complications
Leg traumatic injury
|
10.0%
1/10 • Number of events 1 • 1 year
Adverse Event Monitoring performed on Day 0, Day 1, Week 6, Month 3, and Month 12
|
|
Gastrointestinal disorders
Loss of appetite
|
10.0%
1/10 • Number of events 1 • 1 year
Adverse Event Monitoring performed on Day 0, Day 1, Week 6, Month 3, and Month 12
|
|
Eye disorders
Loss of vision
|
10.0%
1/10 • Number of events 1 • 1 year
Adverse Event Monitoring performed on Day 0, Day 1, Week 6, Month 3, and Month 12
|
|
Musculoskeletal and connective tissue disorders
Lower Back pain
|
10.0%
1/10 • Number of events 1 • 1 year
Adverse Event Monitoring performed on Day 0, Day 1, Week 6, Month 3, and Month 12
|
|
Psychiatric disorders
Major Depressive Disorder
|
10.0%
1/10 • Number of events 1 • 1 year
Adverse Event Monitoring performed on Day 0, Day 1, Week 6, Month 3, and Month 12
|
|
Gastrointestinal disorders
Abdominal Pain
|
10.0%
1/10 • Number of events 1 • 1 year
Adverse Event Monitoring performed on Day 0, Day 1, Week 6, Month 3, and Month 12
|
|
Gastrointestinal disorders
Nausea
|
10.0%
1/10 • Number of events 1 • 1 year
Adverse Event Monitoring performed on Day 0, Day 1, Week 6, Month 3, and Month 12
|
|
Musculoskeletal and connective tissue disorders
Neck pain
|
20.0%
2/10 • Number of events 2 • 1 year
Adverse Event Monitoring performed on Day 0, Day 1, Week 6, Month 3, and Month 12
|
|
Musculoskeletal and connective tissue disorders
Neck stiffness
|
10.0%
1/10 • Number of events 1 • 1 year
Adverse Event Monitoring performed on Day 0, Day 1, Week 6, Month 3, and Month 12
|
|
General disorders
Nosebleeds
|
10.0%
1/10 • Number of events 1 • 1 year
Adverse Event Monitoring performed on Day 0, Day 1, Week 6, Month 3, and Month 12
|
|
Psychiatric disorders
Panic attacks
|
10.0%
1/10 • Number of events 1 • 1 year
Adverse Event Monitoring performed on Day 0, Day 1, Week 6, Month 3, and Month 12
|
|
Psychiatric disorders
Personality Changes
|
10.0%
1/10 • Number of events 1 • 1 year
Adverse Event Monitoring performed on Day 0, Day 1, Week 6, Month 3, and Month 12
|
|
Pregnancy, puerperium and perinatal conditions
Pregnancy
|
10.0%
1/10 • Number of events 1 • 1 year
Adverse Event Monitoring performed on Day 0, Day 1, Week 6, Month 3, and Month 12
|
|
Nervous system disorders
Numbness
|
20.0%
2/10 • Number of events 2 • 1 year
Adverse Event Monitoring performed on Day 0, Day 1, Week 6, Month 3, and Month 12
|
|
Skin and subcutaneous tissue disorders
Scalp Pain
|
10.0%
1/10 • Number of events 1 • 1 year
Adverse Event Monitoring performed on Day 0, Day 1, Week 6, Month 3, and Month 12
|
|
Injury, poisoning and procedural complications
Ankle sprain due to fall
|
10.0%
1/10 • Number of events 2 • 1 year
Adverse Event Monitoring performed on Day 0, Day 1, Week 6, Month 3, and Month 12
|
|
Musculoskeletal and connective tissue disorders
Hip Pain
|
10.0%
1/10 • Number of events 1 • 1 year
Adverse Event Monitoring performed on Day 0, Day 1, Week 6, Month 3, and Month 12
|
|
Ear and labyrinth disorders
Inner Ear pain
|
10.0%
1/10 • Number of events 1 • 1 year
Adverse Event Monitoring performed on Day 0, Day 1, Week 6, Month 3, and Month 12
|
|
Musculoskeletal and connective tissue disorders
Knee pain
|
10.0%
1/10 • Number of events 1 • 1 year
Adverse Event Monitoring performed on Day 0, Day 1, Week 6, Month 3, and Month 12
|
|
Nervous system disorders
Cold sensation leg
|
10.0%
1/10 • Number of events 1 • 1 year
Adverse Event Monitoring performed on Day 0, Day 1, Week 6, Month 3, and Month 12
|
|
Musculoskeletal and connective tissue disorders
Leg cramps
|
20.0%
2/10 • Number of events 3 • 1 year
Adverse Event Monitoring performed on Day 0, Day 1, Week 6, Month 3, and Month 12
|
|
Musculoskeletal and connective tissue disorders
Leg Muscle aches
|
10.0%
1/10 • Number of events 1 • 1 year
Adverse Event Monitoring performed on Day 0, Day 1, Week 6, Month 3, and Month 12
|
|
Musculoskeletal and connective tissue disorders
Partial toenail ingrown
|
10.0%
1/10 • Number of events 1 • 1 year
Adverse Event Monitoring performed on Day 0, Day 1, Week 6, Month 3, and Month 12
|
|
Nervous system disorders
Calf muscle loss of tone
|
10.0%
1/10 • Number of events 1 • 1 year
Adverse Event Monitoring performed on Day 0, Day 1, Week 6, Month 3, and Month 12
|
|
Nervous system disorders
Seizures
|
20.0%
2/10 • Number of events 2 • 1 year
Adverse Event Monitoring performed on Day 0, Day 1, Week 6, Month 3, and Month 12
|
|
Nervous system disorders
Generalized Seizures
|
10.0%
1/10 • Number of events 1 • 1 year
Adverse Event Monitoring performed on Day 0, Day 1, Week 6, Month 3, and Month 12
|
|
Nervous system disorders
Tonic/clonic Seizures
|
10.0%
1/10 • Number of events 2 • 1 year
Adverse Event Monitoring performed on Day 0, Day 1, Week 6, Month 3, and Month 12
|
|
Nervous system disorders
Shot term memory problems
|
10.0%
1/10 • Number of events 1 • 1 year
Adverse Event Monitoring performed on Day 0, Day 1, Week 6, Month 3, and Month 12
|
|
Endocrine disorders
Steroid Induced Hyperglycemia
|
10.0%
1/10 • Number of events 1 • 1 year
Adverse Event Monitoring performed on Day 0, Day 1, Week 6, Month 3, and Month 12
|
|
Eye disorders
Vision loss in left eye
|
10.0%
1/10 • Number of events 1 • 1 year
Adverse Event Monitoring performed on Day 0, Day 1, Week 6, Month 3, and Month 12
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
10.0%
1/10 • Number of events 1 • 1 year
Adverse Event Monitoring performed on Day 0, Day 1, Week 6, Month 3, and Month 12
|
|
Injury, poisoning and procedural complications
Traumatic Fall
|
20.0%
2/10 • Number of events 2 • 1 year
Adverse Event Monitoring performed on Day 0, Day 1, Week 6, Month 3, and Month 12
|
|
Nervous system disorders
Trouble performing simple tasks
|
10.0%
1/10 • Number of events 1 • 1 year
Adverse Event Monitoring performed on Day 0, Day 1, Week 6, Month 3, and Month 12
|
|
Nervous system disorders
Unsteadiness
|
10.0%
1/10 • Number of events 1 • 1 year
Adverse Event Monitoring performed on Day 0, Day 1, Week 6, Month 3, and Month 12
|
|
Respiratory, thoracic and mediastinal disorders
Upper Respiratory Infection
|
10.0%
1/10 • Number of events 1 • 1 year
Adverse Event Monitoring performed on Day 0, Day 1, Week 6, Month 3, and Month 12
|
|
Renal and urinary disorders
Urinary incontinence
|
10.0%
1/10 • Number of events 1 • 1 year
Adverse Event Monitoring performed on Day 0, Day 1, Week 6, Month 3, and Month 12
|
|
Nervous system disorders
Visual seizure
|
10.0%
1/10 • Number of events 1 • 1 year
Adverse Event Monitoring performed on Day 0, Day 1, Week 6, Month 3, and Month 12
|
|
Gastrointestinal disorders
Vomiting
|
20.0%
2/10 • Number of events 2 • 1 year
Adverse Event Monitoring performed on Day 0, Day 1, Week 6, Month 3, and Month 12
|
|
Metabolism and nutrition disorders
Weight Loss
|
10.0%
1/10 • Number of events 1 • 1 year
Adverse Event Monitoring performed on Day 0, Day 1, Week 6, Month 3, and Month 12
|
|
Nervous system disorders
Whole body shaking associated with seizures
|
10.0%
1/10 • Number of events 1 • 1 year
Adverse Event Monitoring performed on Day 0, Day 1, Week 6, Month 3, and Month 12
|
|
Skin and subcutaneous tissue disorders
Worsening Acne on extremities
|
10.0%
1/10 • Number of events 1 • 1 year
Adverse Event Monitoring performed on Day 0, Day 1, Week 6, Month 3, and Month 12
|
|
Cardiac disorders
Worsening chest pain
|
10.0%
1/10 • Number of events 1 • 1 year
Adverse Event Monitoring performed on Day 0, Day 1, Week 6, Month 3, and Month 12
|
|
Nervous system disorders
Worsening of left sided weakness
|
10.0%
1/10 • Number of events 1 • 1 year
Adverse Event Monitoring performed on Day 0, Day 1, Week 6, Month 3, and Month 12
|
|
Skin and subcutaneous tissue disorders
Worsening of striae bilateral arms
|
10.0%
1/10 • Number of events 1 • 1 year
Adverse Event Monitoring performed on Day 0, Day 1, Week 6, Month 3, and Month 12
|
Additional Information
Shervin R. Dashti, MD, PhD, Principal Investigator
Norton Neuroscience Institute
Phone: 502-394-6390
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place