Trial Outcomes & Findings for A Pilot Study To Evaluate The Effects of Everolimus on Brain mTOR Activity and Cortical Hyperexcitability in TSC and FCD (NCT NCT02451696)
NCT ID: NCT02451696
Last Updated: 2021-09-01
Results Overview
.Adverse event monitoring should be continued for at least 30 days (or 5 half-lives, whichever is longer) following the last dose of study treatment
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
15 participants
Primary outcome timeframe
6 weeks
Results posted on
2021-09-01
Participant Flow
Participant milestones
| Measure |
Treated Subjects
This group will be treated with everolimus 7-28 days prior to surgery Everolimus: This study will measure if the drug called Everolimus effects mTOR signaling (an electrical activity signal in the brain) in patients with Tuberous Sclerosis Complex (TSC) and Focal Cortical Dysplasia (FCD) with treatment resistant epilepsy (TRE) who will be undergoing brain surgery. One group of patients will be treated with Everolimus, for 7-28 days prior to epilepsy surgery and another will not. We will determine if there is a difference in mTOR signaling between the patients who were treated with Everolimus and those who were not
|
Reference Subjects
This group will be enrolled as reference subjects, and will be undergoing routine surgery as part of standard of care treatment. No intervention will be provided to these subjects as part of the study
|
|---|---|---|
|
Overall Study
STARTED
|
5
|
10
|
|
Overall Study
COMPLETED
|
4
|
10
|
|
Overall Study
NOT COMPLETED
|
1
|
0
|
Reasons for withdrawal
| Measure |
Treated Subjects
This group will be treated with everolimus 7-28 days prior to surgery Everolimus: This study will measure if the drug called Everolimus effects mTOR signaling (an electrical activity signal in the brain) in patients with Tuberous Sclerosis Complex (TSC) and Focal Cortical Dysplasia (FCD) with treatment resistant epilepsy (TRE) who will be undergoing brain surgery. One group of patients will be treated with Everolimus, for 7-28 days prior to epilepsy surgery and another will not. We will determine if there is a difference in mTOR signaling between the patients who were treated with Everolimus and those who were not
|
Reference Subjects
This group will be enrolled as reference subjects, and will be undergoing routine surgery as part of standard of care treatment. No intervention will be provided to these subjects as part of the study
|
|---|---|---|
|
Overall Study
Surgery postponed
|
1
|
0
|
Baseline Characteristics
A Pilot Study To Evaluate The Effects of Everolimus on Brain mTOR Activity and Cortical Hyperexcitability in TSC and FCD
Baseline characteristics by cohort
| Measure |
Treated Subjects
n=4 Participants
This group will be treated with everolimus 7-28 days prior to surgery
Everolimus: This study will measure if the drug called Everolimus effects mTOR signaling (an electrical activity signal in the brain) in patients with Tuberous Sclerosis Complex (TSC) and Focal Cortical Dysplasia (FCD) with treatment resistant epilepsy (TRE) who will be undergoing brain surgery. One group of patients will be treated with Everolimus, for 7-28 days prior to epilepsy surgery and another will not. We will determine if there is a difference in mTOR signaling between the patients who were treated with Everolimus and those who were not
|
Reference Subjects
n=10 Participants
This group will be enrolled as reference subjects, and will be undergoing routine surgery as part of standard of care treatment. No intervention will be provided to these subjects as part of the study.
|
Total
n=14 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
18.25 years
STANDARD_DEVIATION 10.1 • n=99 Participants
|
13.1 years
STANDARD_DEVIATION 12.3 • n=107 Participants
|
14.6 years
STANDARD_DEVIATION 11.6 • n=206 Participants
|
|
Sex: Female, Male
Female
|
3 Participants
n=99 Participants
|
6 Participants
n=107 Participants
|
9 Participants
n=206 Participants
|
|
Sex: Female, Male
Male
|
1 Participants
n=99 Participants
|
4 Participants
n=107 Participants
|
5 Participants
n=206 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Race (NIH/OMB)
White
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
4 Participants
n=99 Participants
|
10 Participants
n=107 Participants
|
14 Participants
n=206 Participants
|
|
Region of Enrollment
United States
|
4 participants
n=99 Participants
|
10 participants
n=107 Participants
|
14 participants
n=206 Participants
|
PRIMARY outcome
Timeframe: 6 weeks.Adverse event monitoring should be continued for at least 30 days (or 5 half-lives, whichever is longer) following the last dose of study treatment
Outcome measures
| Measure |
Treated Subjects
n=4 Participants
This group will be treated with everolimus 7-28 days prior to surgery
Everolimus: This study will measure if the drug called Everolimus effects mTOR signaling (an electrical activity signal in the brain) in patients with Tuberous Sclerosis Complex (TSC) and Focal Cortical Dysplasia (FCD) with treatment resistant epilepsy (TRE) who will be undergoing brain surgery. One group of patients will be treated with Everolimus, for 7-28 days prior to epilepsy surgery and another will not. We will determine if there is a difference in mTOR signaling between the patients who were treated with Everolimus and those who were not
|
Reference Subjects
n=10 Participants
This group will be enrolled as reference subjects, and will be undergoing routine surgery as part of standard of care treatment. No intervention will be provided to these subjects as part of the study.
|
|---|---|---|
|
Number of Patients With Adverse Events
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: 28 daysmTOR signaling in blood
Outcome measures
| Measure |
Treated Subjects
n=4 Participants
This group will be treated with everolimus 7-28 days prior to surgery
Everolimus: This study will measure if the drug called Everolimus effects mTOR signaling (an electrical activity signal in the brain) in patients with Tuberous Sclerosis Complex (TSC) and Focal Cortical Dysplasia (FCD) with treatment resistant epilepsy (TRE) who will be undergoing brain surgery. One group of patients will be treated with Everolimus, for 7-28 days prior to epilepsy surgery and another will not. We will determine if there is a difference in mTOR signaling between the patients who were treated with Everolimus and those who were not
|
Reference Subjects
n=10 Participants
This group will be enrolled as reference subjects, and will be undergoing routine surgery as part of standard of care treatment. No intervention will be provided to these subjects as part of the study.
|
|---|---|---|
|
Blood Everolimus Levels
|
12.35 ng/ml
Standard Deviation 5.36
|
2 ng/ml
Standard Deviation 0
|
SECONDARY outcome
Timeframe: 28 daysOutcome measures
| Measure |
Treated Subjects
n=4 Participants
This group will be treated with everolimus 7-28 days prior to surgery
Everolimus: This study will measure if the drug called Everolimus effects mTOR signaling (an electrical activity signal in the brain) in patients with Tuberous Sclerosis Complex (TSC) and Focal Cortical Dysplasia (FCD) with treatment resistant epilepsy (TRE) who will be undergoing brain surgery. One group of patients will be treated with Everolimus, for 7-28 days prior to epilepsy surgery and another will not. We will determine if there is a difference in mTOR signaling between the patients who were treated with Everolimus and those who were not
|
Reference Subjects
n=10 Participants
This group will be enrolled as reference subjects, and will be undergoing routine surgery as part of standard of care treatment. No intervention will be provided to these subjects as part of the study.
|
|---|---|---|
|
Blood Total VEGF Levels (Not Only VEGF-D)
|
56.5 pg/ml
Standard Deviation 46.9
|
50.85 pg/ml
Standard Deviation 54.1
|
SECONDARY outcome
Timeframe: 28 daysOutcome measures
| Measure |
Treated Subjects
n=4 Participants
This group will be treated with everolimus 7-28 days prior to surgery
Everolimus: This study will measure if the drug called Everolimus effects mTOR signaling (an electrical activity signal in the brain) in patients with Tuberous Sclerosis Complex (TSC) and Focal Cortical Dysplasia (FCD) with treatment resistant epilepsy (TRE) who will be undergoing brain surgery. One group of patients will be treated with Everolimus, for 7-28 days prior to epilepsy surgery and another will not. We will determine if there is a difference in mTOR signaling between the patients who were treated with Everolimus and those who were not
|
Reference Subjects
n=10 Participants
This group will be enrolled as reference subjects, and will be undergoing routine surgery as part of standard of care treatment. No intervention will be provided to these subjects as part of the study.
|
|---|---|---|
|
mTOR Brain Tissue-S6 Phosphate by Western Blot
|
0.49 normalized val-protein relative to actin
Standard Deviation 0.54
|
0.81 normalized val-protein relative to actin
Standard Deviation 0.22
|
SECONDARY outcome
Timeframe: 28 daysHMGB1 expression is measured through label-free quantification (LFQ). LFQ is a method in mass spectroscopy that determines the relative amount of proteins in biological samples. The unit of measure is LFQ intensity; a higher LFQ intensity indicates greater HMGB1 expression.
Outcome measures
| Measure |
Treated Subjects
n=4 Participants
This group will be treated with everolimus 7-28 days prior to surgery
Everolimus: This study will measure if the drug called Everolimus effects mTOR signaling (an electrical activity signal in the brain) in patients with Tuberous Sclerosis Complex (TSC) and Focal Cortical Dysplasia (FCD) with treatment resistant epilepsy (TRE) who will be undergoing brain surgery. One group of patients will be treated with Everolimus, for 7-28 days prior to epilepsy surgery and another will not. We will determine if there is a difference in mTOR signaling between the patients who were treated with Everolimus and those who were not
|
Reference Subjects
n=10 Participants
This group will be enrolled as reference subjects, and will be undergoing routine surgery as part of standard of care treatment. No intervention will be provided to these subjects as part of the study.
|
|---|---|---|
|
HMGB1 Expression in Brain Tissue
|
14.85 LFQ intensity
Standard Deviation 0.6
|
15.06 LFQ intensity
Standard Deviation 0.35
|
Adverse Events
Treated Subject
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Reference Subject
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
Adverse event data not reported
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place