Trial Outcomes & Findings for Effects of Riluzole on CNS Glutamate and Fatigue in Breast Cancer Survivors With High Inflammation (NCT NCT02796755)
NCT ID: NCT02796755
Last Updated: 2021-04-14
Results Overview
Magnetic resonance spectroscopy (MRS) is a specialized technique associated with magnetic resonance imaging (MRI). MRS is a non-invasive way to obtain biochemical information about the tissues of the human body. Participants underwent single voxel (3-dimensional volume X pixel) MRS to measure CNS glutamate before and after 1 and 8 weeks of riluzole or placebo treatment. Voxels were placed in the right and left basal ganglia and the dorsal anterior cingulate cortex (dACC), well known targets of inflammatory cytokines on the brain, and cytokine effects on these brain regions have been associated with symptoms of fatigue and cognitive dysfunction as well as reduced motivation. MRS has shown that chronic exposure to the inflammatory cytokine interferon (IFN)-alpha leads to increased CNS glutamate (as reflected by the glutamate/creatine (Glu/Cr) ratio) which correlated with symptoms of fatigue and cognitive dysfunction.
COMPLETED
PHASE4
30 participants
Baseline, Week 1, Week 8
2021-04-14
Participant Flow
Participants were enrolled beginning April 2016 and all follow-up visits were complete by October 24, 2019. Participants were enrolled from the patient population at the Emory University Winship Cancer Institute in Atlanta, Georgia.
Participant milestones
| Measure |
Riluzole Arm
Participants took a daily oral dose of 100 mg of riluzole (50 mg two times per day) for 8 weeks. Participants were instructed to take the study medication on an empty stomach (1 hour before or 2 hours after meals).
|
Placebo Arm
Participants took a daily oral dose of 100 mg of a placebo that appears identical to riluzole (50 mg two times per day), for 8 weeks. Participants will be instructed to take the study medication on an empty stomach (1 hour before or 2 hours after meals).
|
|---|---|---|
|
Overall Study
STARTED
|
15
|
15
|
|
Overall Study
COMPLETED
|
13
|
15
|
|
Overall Study
NOT COMPLETED
|
2
|
0
|
Reasons for withdrawal
| Measure |
Riluzole Arm
Participants took a daily oral dose of 100 mg of riluzole (50 mg two times per day) for 8 weeks. Participants were instructed to take the study medication on an empty stomach (1 hour before or 2 hours after meals).
|
Placebo Arm
Participants took a daily oral dose of 100 mg of a placebo that appears identical to riluzole (50 mg two times per day), for 8 weeks. Participants will be instructed to take the study medication on an empty stomach (1 hour before or 2 hours after meals).
|
|---|---|---|
|
Overall Study
Adverse Event
|
2
|
0
|
Baseline Characteristics
Effects of Riluzole on CNS Glutamate and Fatigue in Breast Cancer Survivors With High Inflammation
Baseline characteristics by cohort
| Measure |
Riluzole Arm
n=15 Participants
Participants took a daily oral dose of 100 mg of riluzole (50 mg two times per day) for 8 weeks. Participants were instructed to take the study medication on an empty stomach (1 hour before or 2 hours after meals).
|
Placebo Arm
n=15 Participants
Participants took a daily oral dose of 100 mg of a placebo that appears identical to riluzole (50 mg two times per day), for 8 weeks. Participants will be instructed to take the study medication on an empty stomach (1 hour before or 2 hours after meals).
|
Total
n=30 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
15 Participants
n=99 Participants
|
15 Participants
n=107 Participants
|
30 Participants
n=206 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Age, Continuous
|
54.2 years
STANDARD_DEVIATION 6.7 • n=99 Participants
|
53.7 years
STANDARD_DEVIATION 5.3 • n=107 Participants
|
53.9 years
STANDARD_DEVIATION 5.9 • n=206 Participants
|
|
Sex: Female, Male
Female
|
15 Participants
n=99 Participants
|
15 Participants
n=107 Participants
|
30 Participants
n=206 Participants
|
|
Sex: Female, Male
Male
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
15 Participants
n=99 Participants
|
15 Participants
n=107 Participants
|
30 Participants
n=206 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 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
|
11 Participants
n=99 Participants
|
7 Participants
n=107 Participants
|
18 Participants
n=206 Participants
|
|
Race (NIH/OMB)
White
|
4 Participants
n=99 Participants
|
8 Participants
n=107 Participants
|
12 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
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Region of Enrollment
United States
|
15 Participants
n=99 Participants
|
15 Participants
n=107 Participants
|
30 Participants
n=206 Participants
|
PRIMARY outcome
Timeframe: Baseline, Week 1, Week 8Magnetic resonance spectroscopy (MRS) is a specialized technique associated with magnetic resonance imaging (MRI). MRS is a non-invasive way to obtain biochemical information about the tissues of the human body. Participants underwent single voxel (3-dimensional volume X pixel) MRS to measure CNS glutamate before and after 1 and 8 weeks of riluzole or placebo treatment. Voxels were placed in the right and left basal ganglia and the dorsal anterior cingulate cortex (dACC), well known targets of inflammatory cytokines on the brain, and cytokine effects on these brain regions have been associated with symptoms of fatigue and cognitive dysfunction as well as reduced motivation. MRS has shown that chronic exposure to the inflammatory cytokine interferon (IFN)-alpha leads to increased CNS glutamate (as reflected by the glutamate/creatine (Glu/Cr) ratio) which correlated with symptoms of fatigue and cognitive dysfunction.
Outcome measures
| Measure |
Riluzole Arm
n=15 Participants
Participants took a daily oral dose of 100 mg of riluzole (50 mg two times per day) for 8 weeks. Participants were instructed to take the study medication on an empty stomach (1 hour before or 2 hours after meals).
|
Placebo Arm
n=15 Participants
Participants took a daily oral dose of 100 mg of a placebo that appears identical to riluzole (50 mg two times per day), for 8 weeks. Participants will be instructed to take the study medication on an empty stomach (1 hour before or 2 hours after meals).
|
|---|---|---|
|
Central Nervous System (CNS) Glutamate Measured by Magnetic Resonance Spectroscopy (MRS)
Baseline dorsal anterior cingulate cortex (dACC)
|
1.26 Glu/Cr
Standard Deviation 0.09
|
1.2 Glu/Cr
Standard Deviation 0.15
|
|
Central Nervous System (CNS) Glutamate Measured by Magnetic Resonance Spectroscopy (MRS)
Week 1 dACC
|
1.26 Glu/Cr
Standard Deviation 1.26
|
1.27 Glu/Cr
Standard Deviation 0.12
|
|
Central Nervous System (CNS) Glutamate Measured by Magnetic Resonance Spectroscopy (MRS)
Week 8 dACC
|
1.27 Glu/Cr
Standard Deviation 0.12
|
1.27 Glu/Cr
Standard Deviation 0.07
|
|
Central Nervous System (CNS) Glutamate Measured by Magnetic Resonance Spectroscopy (MRS)
Baseline left basal ganglia
|
0.85 Glu/Cr
Standard Deviation 0.09
|
0.91 Glu/Cr
Standard Deviation 0.12
|
|
Central Nervous System (CNS) Glutamate Measured by Magnetic Resonance Spectroscopy (MRS)
Week 1 left basal ganglia
|
0.93 Glu/Cr
Standard Deviation 0.16
|
0.96 Glu/Cr
Standard Deviation 0.13
|
|
Central Nervous System (CNS) Glutamate Measured by Magnetic Resonance Spectroscopy (MRS)
Week 8 left basal ganglia
|
0.96 Glu/Cr
Standard Deviation 0.2
|
0.98 Glu/Cr
Standard Deviation 0.11
|
|
Central Nervous System (CNS) Glutamate Measured by Magnetic Resonance Spectroscopy (MRS)
Baseline right basal ganglia
|
0.9 Glu/Cr
Standard Deviation 0.09
|
0.92 Glu/Cr
Standard Deviation 0.14
|
|
Central Nervous System (CNS) Glutamate Measured by Magnetic Resonance Spectroscopy (MRS)
Week 1 right basal ganglia
|
0.9 Glu/Cr
Standard Deviation 0.08
|
0.89 Glu/Cr
Standard Deviation 0.11
|
|
Central Nervous System (CNS) Glutamate Measured by Magnetic Resonance Spectroscopy (MRS)
Week 8 right basal ganglia
|
0.93 Glu/Cr
Standard Deviation 0.13
|
0.93 Glu/Cr
Standard Deviation 0.1
|
SECONDARY outcome
Timeframe: Baseline, Weeks 1, 2, 4, 8The Multidimensional Fatigue Inventory (MFI) is a 20-item scale used to evaluate the presence and severity of fatigue among subjects by self-reports. The MFI assesses 5 dimensions of fatigue, including general fatigue, physical fatigue, mental fatigue, reduced activity, and reduced motivation. Participants respond to fatigue related statements using a 5 point scale where 1 = "yes, that is true" and 5 = "no, that is not true". Total scores range from 20 to 100 and higher scores indicate greater fatigue.
Outcome measures
| Measure |
Riluzole Arm
n=15 Participants
Participants took a daily oral dose of 100 mg of riluzole (50 mg two times per day) for 8 weeks. Participants were instructed to take the study medication on an empty stomach (1 hour before or 2 hours after meals).
|
Placebo Arm
n=15 Participants
Participants took a daily oral dose of 100 mg of a placebo that appears identical to riluzole (50 mg two times per day), for 8 weeks. Participants will be instructed to take the study medication on an empty stomach (1 hour before or 2 hours after meals).
|
|---|---|---|
|
Multidimensional Fatigue Inventory (MFI) Score
Week 8
|
58.92 score on a scale
Standard Deviation 16.47
|
46.50 score on a scale
Standard Deviation 13.85
|
|
Multidimensional Fatigue Inventory (MFI) Score
Baseline
|
66.90 score on a scale
Standard Deviation 10.99
|
58.90 score on a scale
Standard Deviation 13.86
|
|
Multidimensional Fatigue Inventory (MFI) Score
Week 1
|
63.80 score on a scale
Standard Deviation 12.10
|
53.50 score on a scale
Standard Deviation 15.80
|
|
Multidimensional Fatigue Inventory (MFI) Score
Week 2
|
62.00 score on a scale
Standard Deviation 14.60
|
53.21 score on a scale
Standard Deviation 16.85
|
|
Multidimensional Fatigue Inventory (MFI) Score
Week 4
|
61.07 score on a scale
Standard Deviation 12.40
|
51.14 score on a scale
Standard Deviation 15.64
|
SECONDARY outcome
Timeframe: Baseline, Weeks 1, 2, 4, 8PROMIS-Fatigue Short Form is a 7-item scale developed by the Patient-Reported Outcome Measurement Information System (PROMIS), a part of the NIH Roadmap Initiative which is focused on developing a publicly available resource of standardized, accurate, and efficient outcome measures of symptoms, distress, and functioning. The criterion for a minimally clinically important difference in patients with advanced-stage cancer is a 3 to 5 point difference in raw score. Recommendations for high priority research on cancer-related fatigue recommend use of the PROMIS fatigue scale to allow comparison of results across studies. Respondents indicate how much they agree with the item statements on a scale from 1 (not at all) to 5 (very much). Total scores range from 7 to 35 with higher scores indicating greater fatigue.
Outcome measures
| Measure |
Riluzole Arm
n=15 Participants
Participants took a daily oral dose of 100 mg of riluzole (50 mg two times per day) for 8 weeks. Participants were instructed to take the study medication on an empty stomach (1 hour before or 2 hours after meals).
|
Placebo Arm
n=15 Participants
Participants took a daily oral dose of 100 mg of a placebo that appears identical to riluzole (50 mg two times per day), for 8 weeks. Participants will be instructed to take the study medication on an empty stomach (1 hour before or 2 hours after meals).
|
|---|---|---|
|
Patient-Reported Outcomes Measurement Information System (PROMIS) - Fatigue Short Form Score
Baseline
|
25.1 score on a scale
Standard Deviation 3.8
|
21.8 score on a scale
Standard Deviation 5.0
|
|
Patient-Reported Outcomes Measurement Information System (PROMIS) - Fatigue Short Form Score
Week 1
|
22.5 score on a scale
Standard Deviation 4.3
|
18.71 score on a scale
Standard Deviation 5.06
|
|
Patient-Reported Outcomes Measurement Information System (PROMIS) - Fatigue Short Form Score
Week 2
|
23.7 score on a scale
Standard Deviation 5.5
|
17.07 score on a scale
Standard Deviation 6.18
|
|
Patient-Reported Outcomes Measurement Information System (PROMIS) - Fatigue Short Form Score
Week 4
|
21.6 score on a scale
Standard Deviation 5.8
|
17.36 score on a scale
Standard Deviation 6.07
|
|
Patient-Reported Outcomes Measurement Information System (PROMIS) - Fatigue Short Form Score
Week 8
|
18.8 score on a scale
Standard Deviation 6.1
|
15.07 score on a scale
Standard Deviation 6.11
|
Adverse Events
Riluzole Arm
Placebo Arm
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Riluzole Arm
n=15 participants at risk
Participants took a daily oral dose of 100 mg of riluzole (50 mg two times per day) for 8 weeks. Participants were instructed to take the study medication on an empty stomach (1 hour before or 2 hours after meals).
|
Placebo Arm
n=15 participants at risk
Participants took a daily oral dose of 100 mg of a placebo that appears identical to riluzole (50 mg two times per day), for 8 weeks. Participants will be instructed to take the study medication on an empty stomach (1 hour before or 2 hours after meals).
|
|---|---|---|
|
General disorders
Headache
|
26.7%
4/15 • Number of events 4 • Information on adverse events was collected from the time consent to participate in the study was given through the Week 8 study visit.
|
13.3%
2/15 • Number of events 2 • Information on adverse events was collected from the time consent to participate in the study was given through the Week 8 study visit.
|
|
Gastrointestinal disorders
Gastrointestinal distress
|
40.0%
6/15 • Number of events 6 • Information on adverse events was collected from the time consent to participate in the study was given through the Week 8 study visit.
|
20.0%
3/15 • Number of events 3 • Information on adverse events was collected from the time consent to participate in the study was given through the Week 8 study visit.
|
|
Skin and subcutaneous tissue disorders
Itch/Rash
|
13.3%
2/15 • Number of events 2 • Information on adverse events was collected from the time consent to participate in the study was given through the Week 8 study visit.
|
0.00%
0/15 • Information on adverse events was collected from the time consent to participate in the study was given through the Week 8 study visit.
|
|
General disorders
Fatigue
|
6.7%
1/15 • Number of events 1 • Information on adverse events was collected from the time consent to participate in the study was given through the Week 8 study visit.
|
0.00%
0/15 • Information on adverse events was collected from the time consent to participate in the study was given through the Week 8 study visit.
|
|
General disorders
Irritability
|
6.7%
1/15 • Number of events 1 • Information on adverse events was collected from the time consent to participate in the study was given through the Week 8 study visit.
|
6.7%
1/15 • Number of events 1 • Information on adverse events was collected from the time consent to participate in the study was given through the Week 8 study visit.
|
|
General disorders
Paresthesia
|
0.00%
0/15 • Information on adverse events was collected from the time consent to participate in the study was given through the Week 8 study visit.
|
6.7%
1/15 • Number of events 1 • Information on adverse events was collected from the time consent to participate in the study was given through the Week 8 study visit.
|
|
General disorders
Increased white blood cell count
|
0.00%
0/15 • Information on adverse events was collected from the time consent to participate in the study was given through the Week 8 study visit.
|
6.7%
1/15 • Number of events 1 • Information on adverse events was collected from the time consent to participate in the study was given through the Week 8 study visit.
|
|
Surgical and medical procedures
Venipuncture complications
|
13.3%
2/15 • Number of events 2 • Information on adverse events was collected from the time consent to participate in the study was given through the Week 8 study visit.
|
0.00%
0/15 • Information on adverse events was collected from the time consent to participate in the study was given through the Week 8 study visit.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place