Trial Outcomes & Findings for Riluzole in Mild Alzheimer's Disease (NCT NCT01703117)
NCT ID: NCT01703117
Last Updated: 2021-09-22
Results Overview
Change from baseline to 6 months in cerebral glucose metabolism measured with FDG PET in posterior cingulate cortex, hippocampus, precuneus, and medial temporal, lateral temporal, inferior parietal, and frontal lobes, referred to collectively as our pre-specified regions of interest. Fluorodeoxyglucose (FDG)-positron emission tomography (PET) is an imaging procedure that measures glucose metabolism in the brain.It is a well-established Alzheimer's disease biomarker and predictor of disease progression. For each FDG PET scan, 5 mCi of fluorodeoxyglucose was administered followed by a 40 minute uptake period during which the participant was in a resting state. Images were acquired on a Siemens Biograph 64mCT scanner as a series of 4 frames of 5 minutes each. Using SPM12 (Wellcome Trust), motion correction was performed and frames averaged into a static image. Each 6 month scan was coregistered to the baseline FDG scan, which was co-registered to the participant's T1-weighted MRI scan.
COMPLETED
PHASE2
50 participants
Change from baseline to 6 months
2021-09-22
Participant Flow
Participant milestones
| Measure |
Riluzole
Riluzole 50mg twice a day
|
Placebo
Matching placebo twice a day
|
|---|---|---|
|
Overall Study
STARTED
|
26
|
24
|
|
Overall Study
COMPLETED
|
22
|
20
|
|
Overall Study
NOT COMPLETED
|
4
|
4
|
Reasons for withdrawal
| Measure |
Riluzole
Riluzole 50mg twice a day
|
Placebo
Matching placebo twice a day
|
|---|---|---|
|
Overall Study
Adverse Event
|
4
|
3
|
|
Overall Study
Withdrawal by Subject
|
0
|
1
|
Baseline Characteristics
Riluzole in Mild Alzheimer's Disease
Baseline characteristics by cohort
| Measure |
Placebo
n=20 Participants
Matching placebo twice a day
|
Riluzole
n=22 Participants
Riluzole 50mg twice a day
|
Total
n=42 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
74.6 years
STANDARD_DEVIATION 7.7 • n=5 Participants
|
75.3 years
STANDARD_DEVIATION 5.8 • n=7 Participants
|
74.98 years
STANDARD_DEVIATION 6.7 • n=5 Participants
|
|
Sex: Female, Male
Female
|
14 Participants
n=5 Participants
|
12 Participants
n=7 Participants
|
26 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
6 Participants
n=5 Participants
|
10 Participants
n=7 Participants
|
16 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Black or African American
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Black/non-Hispanic
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Latino/Hispanic
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
White/non-Hispanic
|
19 Participants
n=5 Participants
|
20 Participants
n=7 Participants
|
39 Participants
n=5 Participants
|
|
Education
|
15.1 years
STANDARD_DEVIATION 3.1 • n=5 Participants
|
15.9 years
STANDARD_DEVIATION 3.0 • n=7 Participants
|
15.5 years
STANDARD_DEVIATION 3.0 • n=5 Participants
|
PRIMARY outcome
Timeframe: Change from baseline to 6 monthsChange from baseline to 6 months in cerebral glucose metabolism measured with FDG PET in posterior cingulate cortex, hippocampus, precuneus, and medial temporal, lateral temporal, inferior parietal, and frontal lobes, referred to collectively as our pre-specified regions of interest. Fluorodeoxyglucose (FDG)-positron emission tomography (PET) is an imaging procedure that measures glucose metabolism in the brain.It is a well-established Alzheimer's disease biomarker and predictor of disease progression. For each FDG PET scan, 5 mCi of fluorodeoxyglucose was administered followed by a 40 minute uptake period during which the participant was in a resting state. Images were acquired on a Siemens Biograph 64mCT scanner as a series of 4 frames of 5 minutes each. Using SPM12 (Wellcome Trust), motion correction was performed and frames averaged into a static image. Each 6 month scan was coregistered to the baseline FDG scan, which was co-registered to the participant's T1-weighted MRI scan.
Outcome measures
| Measure |
Placebo
n=20 Participants
Matching placebo twice a day
|
Riluzole
n=22 Participants
Riluzole 50mg twice a day
|
|---|---|---|
|
Imaging Biomarkers FDG-PET SUVR in Regions of Interest
Posterior cingulate
|
-0.048 Standardized Uptake Value Ratios (SUVRs)
Standard Deviation 0.035
|
-0.005 Standardized Uptake Value Ratios (SUVRs)
Standard Deviation 0.035
|
|
Imaging Biomarkers FDG-PET SUVR in Regions of Interest
Precuneus
|
-0.032 Standardized Uptake Value Ratios (SUVRs)
Standard Deviation 0.028
|
-0.007 Standardized Uptake Value Ratios (SUVRs)
Standard Deviation 0.032
|
|
Imaging Biomarkers FDG-PET SUVR in Regions of Interest
Temporal
|
-0.023 Standardized Uptake Value Ratios (SUVRs)
Standard Deviation 0.033
|
0.002 Standardized Uptake Value Ratios (SUVRs)
Standard Deviation 0.029
|
|
Imaging Biomarkers FDG-PET SUVR in Regions of Interest
Frontal
|
-0.129 Standardized Uptake Value Ratios (SUVRs)
Standard Deviation 0.066
|
-0.077 Standardized Uptake Value Ratios (SUVRs)
Standard Deviation 0.072
|
|
Imaging Biomarkers FDG-PET SUVR in Regions of Interest
Parietal
|
-0.020 Standardized Uptake Value Ratios (SUVRs)
Standard Deviation 0.027
|
-0.005 Standardized Uptake Value Ratios (SUVRs)
Standard Deviation 0.024
|
|
Imaging Biomarkers FDG-PET SUVR in Regions of Interest
Hippocampus
|
-0.018 Standardized Uptake Value Ratios (SUVRs)
Standard Deviation 0.034
|
-0.002 Standardized Uptake Value Ratios (SUVRs)
Standard Deviation 0.029
|
|
Imaging Biomarkers FDG-PET SUVR in Regions of Interest
Right Hippocampus
|
-0.021 Standardized Uptake Value Ratios (SUVRs)
Standard Deviation 0.036
|
0.002 Standardized Uptake Value Ratios (SUVRs)
Standard Deviation 0.027
|
|
Imaging Biomarkers FDG-PET SUVR in Regions of Interest
AD Progression score
|
0.579 Standardized Uptake Value Ratios (SUVRs)
Standard Deviation 0.607
|
0.245 Standardized Uptake Value Ratios (SUVRs)
Standard Deviation 0.558
|
|
Imaging Biomarkers FDG-PET SUVR in Regions of Interest
Post Cing - Precuneus
|
-0.041 Standardized Uptake Value Ratios (SUVRs)
Standard Deviation 0.042
|
-0.006 Standardized Uptake Value Ratios (SUVRs)
Standard Deviation 0.038
|
|
Imaging Biomarkers FDG-PET SUVR in Regions of Interest
Orbitofrontal
|
-0.019 Standardized Uptake Value Ratios (SUVRs)
Standard Deviation 0.044
|
0.014 Standardized Uptake Value Ratios (SUVRs)
Standard Deviation 0.036
|
PRIMARY outcome
Timeframe: Changes from baseline to 6 monthsPopulation: Some participants could not complete MRS study due to multiple reasons (eg could not tolerate lengthy exam, did not return to visit etc) or did complete it but quality control of the MRS spectra did not pass screening criteria for analysis.
N-acetylaspartate (NAA) is a neuronal viability marker measured through magnetic resonance spectroscopy (1H MRS).In vivo brain levels of NAA, glutamate, tCr and other major metabolites were obtained using 1H MRS and a 2x2x2-cm3 Posterior Cingulate Cortex (PC) voxel of interest in approximately 6.5 minutes using the constant-time point-resolved spectroscopy (CT-PRESS) technique with TE 30 ms, 129 constant-time increments (t1) of 0.8ms, and TR 1500 ms and a receive-only 8-channel phased-array head coil.The levels of NAA and other metabolites were expressed semi-quantitatively as ratios of peak areas relative to that of the unsuppressed water signal (W) from the same voxels. For consistency with earlier MRS literature, levels of the same metabolites were also expressed as peak ratios relative to tCr area in the same voxel.
Outcome measures
| Measure |
Placebo
n=19 Participants
Matching placebo twice a day
|
Riluzole
n=19 Participants
Riluzole 50mg twice a day
|
|---|---|---|
|
Imaging Biomarkers N-acetylaspartate (NAA) in Posterior Cingulate (PC) Measured Through 1H MRS
BASELINE (NAA/W)
|
0.3843874 Ratios
Standard Deviation 0.0815156
|
0.4274546 Ratios
Standard Deviation 0.0684472
|
|
Imaging Biomarkers N-acetylaspartate (NAA) in Posterior Cingulate (PC) Measured Through 1H MRS
3 MONTHS (NAA/W)
|
0.3996655 Ratios
Standard Deviation 0.0927727
|
0.4248429 Ratios
Standard Deviation 0.0774599
|
|
Imaging Biomarkers N-acetylaspartate (NAA) in Posterior Cingulate (PC) Measured Through 1H MRS
6 MONTHS (NAA/W)
|
0.3784181 Ratios
Standard Deviation 0.0758756
|
0.4415926 Ratios
Standard Deviation 0.1039630
|
|
Imaging Biomarkers N-acetylaspartate (NAA) in Posterior Cingulate (PC) Measured Through 1H MRS
BASELINE (NAA/tCr)
|
1.4488809 Ratios
Standard Deviation 0.1731644
|
1.4802620 Ratios
Standard Deviation 0.1412636
|
|
Imaging Biomarkers N-acetylaspartate (NAA) in Posterior Cingulate (PC) Measured Through 1H MRS
3 MONTHS (NAA/tCr)
|
1.4271889 Ratios
Standard Deviation 0.1140340
|
1.4766125 Ratios
Standard Deviation 0.1304353
|
|
Imaging Biomarkers N-acetylaspartate (NAA) in Posterior Cingulate (PC) Measured Through 1H MRS
6 MONTHS (NAA/tCr)
|
1.4594796 Ratios
Standard Deviation 0.1458860
|
1.4811814 Ratios
Standard Deviation 0.1474927
|
SECONDARY outcome
Timeframe: Change from baseline to 6 monthsPopulation: Some participants could not complete MRS study due to multiple reasons (eg could not tolerate lengthy exam, did not return to visit etc) or did complete it but quality control of the MRS spectra did not pass screening criteria for analysis.
In vivo measurement of glutamate with 1H magnetic resonance spectroscopy (MRS) (a neuroimaging study) in posterior cingulate as a marker of target engagement at three and six months compared to baseline.In vivo brain levels of glutamate, tCr and other major metabolites were obtained using 1H MRS and a 2x2x2-cm3 Posterior Cingulate Cortex voxel of interest in approximately 6.5 minutes using the constant-time point-resolved spectroscopy (CT-PRESS) technique with TE 30 ms, 129 constant-time increments (t1) of 0.8ms, and TR 1500 ms and a receive-only 8-channel phased-array head coil.The levels of glutamate and other metabolites were expressed semi-quantitatively as ratios of peak areas relative to that of the unsuppressed water signal (W) from the same voxels. For consistency with earlier MRS literature, levels of the same metabolites were also expressed as peak ratios relative to tCr area in the same voxel.
Outcome measures
| Measure |
Placebo
n=19 Participants
Matching placebo twice a day
|
Riluzole
n=19 Participants
Riluzole 50mg twice a day
|
|---|---|---|
|
Glutamate Levels Measured Through 1H MRS
BASELINE (Glu/W)
|
0.0598059 Ratios
Standard Deviation 0.0164069
|
0.0677906 Ratios
Standard Deviation 0.0133271
|
|
Glutamate Levels Measured Through 1H MRS
3 MONTHS (Glu/W)
|
0.0579899 Ratios
Standard Deviation 0.0181040
|
0.0646162 Ratios
Standard Deviation 0.0107094
|
|
Glutamate Levels Measured Through 1H MRS
6 MONTHS (Glu/W)
|
0.0609985 Ratios
Standard Deviation 0.0156960
|
0.0633453 Ratios
Standard Deviation 0.0147764
|
|
Glutamate Levels Measured Through 1H MRS
BASELINE (Glu/tCr)
|
0.2280186 Ratios
Standard Deviation 0.0543718
|
0.2367567 Ratios
Standard Deviation 0.0484442
|
|
Glutamate Levels Measured Through 1H MRS
3 MONTHS (Glu/tCr)
|
0.2080647 Ratios
Standard Deviation 0.0515160
|
0.2285644 Ratios
Standard Deviation 0.0441709
|
|
Glutamate Levels Measured Through 1H MRS
6 MONTHS (Glu/tCr)
|
0.2339366 Ratios
Standard Deviation 0.0370164
|
0.2162526 Ratios
Standard Deviation 0.0426140
|
SECONDARY outcome
Timeframe: baseline to 6 monthsThe ADAS comprises two subscales, cognitive and non-cognitive. The Cognitive Subscale (ADAScog) is a psychometric instrument that includes 11 tasks and evaluates memory, attention, reasoning, language, orientation, and praxis, scored from 0 to 70. The full ADAS total is scored by summing the number of errors made on each task on a range from 0 to 150 so that higher scores indicate worse performance.The non-cognitive component was not used in this study. Obtained for correlation with neuroimaging biomarkers.
Outcome measures
| Measure |
Placebo
n=22 Participants
Matching placebo twice a day
|
Riluzole
n=20 Participants
Riluzole 50mg twice a day
|
|---|---|---|
|
Alzheimer's Disease Assessment Scale (ADAS) - Cognitive Subscale (ADAScog)
BASELINE
|
22.4981818 score on a scale
Standard Deviation 7.8875264
|
17.9005000 score on a scale
Standard Deviation 7.4614719
|
|
Alzheimer's Disease Assessment Scale (ADAS) - Cognitive Subscale (ADAScog)
6 MONTHS
|
21.8022727 score on a scale
Standard Deviation 9.7334313
|
18.8495000 score on a scale
Standard Deviation 9.2608983
|
SECONDARY outcome
Timeframe: baseline to 6 monthsNPI assesses psychopathology in participants with dementia and other neurologic disorders. Information is obtained from a caregiver familiar with the participant's behavior. Total score ranges from 0 to 144; Higher scores indicate greater disease severity. Obtained for correlation with neuroimaging
Outcome measures
| Measure |
Placebo
n=22 Participants
Matching placebo twice a day
|
Riluzole
n=20 Participants
Riluzole 50mg twice a day
|
|---|---|---|
|
Neuropsychiatry Inventory - NPI
6 MONTHS
|
9.0909091 score on a scale
Standard Deviation 6.6254135
|
14.0500000 score on a scale
Standard Deviation 12.8082005
|
|
Neuropsychiatry Inventory - NPI
BASELINE
|
9.6363636 score on a scale
Standard Deviation 9.1627894
|
10.2000000 score on a scale
Standard Deviation 11.1383642
|
SECONDARY outcome
Timeframe: baseline to 6 monthsADCS-ADL is a 23-item inventory developed as a Rater-administered questionnaire answered by the participant's caregiver. It measures performance of basic and instrumental activities of daily living by participants. The total score ranges from 0 to 78, with lower scores indicating greater disease severity. Obtained for correlation with neuroimaging
Outcome measures
| Measure |
Placebo
n=22 Participants
Matching placebo twice a day
|
Riluzole
n=20 Participants
Riluzole 50mg twice a day
|
|---|---|---|
|
ADCS Activities of Daily Living
BASELINE
|
68.3636364 score on a scale
Standard Deviation 9.5096215
|
68.0500000 score on a scale
Standard Deviation 9.3215935
|
|
ADCS Activities of Daily Living
6 MONTHS
|
65.5000000 score on a scale
Standard Deviation 11.5377228
|
64.3000000 score on a scale
Standard Deviation 10.7757037
|
Adverse Events
Riluzole
Placebo
Serious adverse events
| Measure |
Riluzole
n=26 participants at risk
Riluzole 50mg twice a day
|
Placebo
n=24 participants at risk
Matching placebo twice a day
|
|---|---|---|
|
Gastrointestinal disorders
GI
|
3.8%
1/26 • Number of events 1 • 6 months
|
0.00%
0/24 • 6 months
|
|
Blood and lymphatic system disorders
Blood disorder
|
3.8%
1/26 • Number of events 1 • 6 months
|
0.00%
0/24 • 6 months
|
|
Cardiac disorders
Cardiac
|
0.00%
0/26 • 6 months
|
4.2%
1/24 • Number of events 1 • 6 months
|
Other adverse events
| Measure |
Riluzole
n=26 participants at risk
Riluzole 50mg twice a day
|
Placebo
n=24 participants at risk
Matching placebo twice a day
|
|---|---|---|
|
Gastrointestinal disorders
Abdominal discomfort
|
15.4%
4/26 • 6 months
|
0.00%
0/24 • 6 months
|
|
Gastrointestinal disorders
Diarrhea
|
15.4%
4/26 • 6 months
|
8.3%
2/24 • 6 months
|
|
General disorders
Dizziness
|
15.4%
4/26 • 6 months
|
4.2%
1/24 • 6 months
|
|
Renal and urinary disorders
Urinary frequency
|
11.5%
3/26 • 6 months
|
0.00%
0/24 • 6 months
|
|
Gastrointestinal disorders
Nausea
|
7.7%
2/26 • 6 months
|
0.00%
0/24 • 6 months
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
19.2%
5/26 • 6 months
|
12.5%
3/24 • 6 months
|
|
Hepatobiliary disorders
Elevated liver enzymes
|
7.7%
2/26 • 6 months
|
4.2%
1/24 • 6 months
|
|
Psychiatric disorders
Anxiety
|
7.7%
2/26 • 6 months
|
16.7%
4/24 • 6 months
|
|
Psychiatric disorders
Paranoia
|
3.8%
1/26 • 6 months
|
12.5%
3/24 • 6 months
|
|
Skin and subcutaneous tissue disorders
Rash
|
3.8%
1/26 • 6 months
|
8.3%
2/24 • 6 months
|
|
General disorders
Fatigue
|
3.8%
1/26 • 6 months
|
8.3%
2/24 • 6 months
|
|
General disorders
Somnolence
|
0.00%
0/26 • 6 months
|
12.5%
3/24 • 6 months
|
|
Musculoskeletal and connective tissue disorders
Back Pain
|
7.7%
2/26 • 6 months
|
8.3%
2/24 • 6 months
|
Additional Information
Dr. Ana Pereira
Icahn School of Medicine at Mount Sinai
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place