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CompletedPhase 2Results posted

Riluzole in Mild Alzheimer's Disease

Glutamatergic Dysfunction in Cognitive Aging: Riluzole in Mild Alzheimer's Disease

Lead sponsor

Icahn School of Medicine at Mount Sinai

Asset

Riluzole

Listed sites

Recruiting sites

Enrollment

actual

Study population

Alzheimer’s disease

Key I/E criteria

•MMSE 19-27•MRI contraindications excluded

Primary endpoints

•Imaging Biomarkers FDG-PET SUVR in Regions of Interest•Imaging Biomarkers N-acetylaspartate (NAA) in Posterior Cingulate (PC) Measured

Footprint

Where this trial recruits

Site locations as reported to ClinicalTrials.gov. Site count is not enrollment count; per-site enrollment is not available from source.

Identifiers

Registered as

Secondary IDAPE-0792Rockefeller University

Org study IDGCO 18-0623

NCT IDNCT01703117

Timeline

Milestones

Study first posted2012-10-10estimated

Study start2013-11actual (month precision)

Primary completion2020-05-26actual

Study completion2020-05-26actual

Last update posted2021-09-22actual

Results first posted2021-09-22actual

Assets

Drug assets

Riluzole

Study populations

Who this study enrolls

Alzheimer’s disease

Eligibility

Who can enroll

Minimum age50 Years

Maximum age95 Years

SexAll

Healthy volunteersNot accepted

Inclusion criteria

•Male or female; 50 - 95 years old with mild Alzheimer's disease determined after neurological and neuropsychological evaluation following the National Institute on Aging - Alzheimer's disease Association criteria that recently revisited the NINCDS-ADRDA criteria. For mild Alzheimer's disease, Clinical Dementia Ratings Scale (CDR) should be 0.5 or 1 and Mini Mental State Examination (MMSS) between 19 and 27.

•Must be on donepezil (Aricept®) or rivastigmine (Exelon®) or galantamine (Razadyne®) at a consistent dose for at least 2 months. Patients will be considered for inclusion if they were previously unable to tolerate acetylcholinesterase inhibitors and as a result, are no longer on the medication for at least 2 months.

•Must be fluent in English

•The subject will appoint or have previously appointed a health care proxy specifically designated for research consent and that this be documented

Exclusion criteria

•Severe Alzheimer's disease and other dementias as determined by neuropsychological testing and neurological evaluation.

•Previous riluzole treatment.

•MRI contraindication (severe claustrophobia, metal implants, shunts, pacemaker, joint implants, metal valves).

•Currently taking medications that either have evidence of glutamatergic activity or has previous MRS evidence of effects on brain glutamate levels at the discretion of the PI such as memantine, lamotrigine, lithium, opiates, bupropion, psychostimulants such as amphetamines and methylphenidate, tricyclic antidepressants, benzodiazepines and any other drug that the investigators judge might interfere with the study. (subjects on those medications may still be included in the study however only the values of NAA from MRS will be utilized and not the glutamate measurements).

•Currently a user of the following illicit drugs: cocaine, methylenedioxymethamphetamine (MDMA) ("ecstasy"), heroin and other opioids or has a history of drug or alcohol abuse within the past 5 years.

•Serum creatinine >1.5 times the upper limit of normal.

•Abnormal liver function test (greater than 2 times the upper limit of normal for alanine aminotransferase (ALT) or aspartate aminotransferase (AST); or bilirubin >1.5 times the upper limit of normal.

•History of brain disease including Parkinson's Disease, severe brain trauma, seizures, history of stroke, clinically significant lacunar infarct in a region important for cognition or multiple lacunes or a cortical infarct or focal lesions of clinical significance, multiple sclerosis, mental retardation, normal pressure hydrocephalus, central nervous system (CNS) tumor, Huntington's disease, subdural hematoma or other serious neurological disorder.

•Uncontrolled diabetes mellitus (Hba1c higher than 7) or chronically uncontrolled hypertension.

•Subject must not be taking Namenda® (memantine) for 6-weeks prior to study entrance.

•Currently taking any concomitant hepatotoxic drugs such as allopurinol, methyldopa and sulfasalazine.

•Any unstable serious co-existing medical condition(s) including but not limited to myocardial infarction, coronary artery disease requiring coronary bypass surgery, unstable angina, clinically evident congestive heart failure within 6 months prior to the screening visit.

•Current smoker or user of nicotine-containing products, such as chewing tobacco, nicotine patch or gum for the past 2 months.

•Current untreated major depression defined by Geriatric Depression Scale > 20.

•Participation in any investigational or marketed drug or device trial within 30 days prior to the screening visit.

•Significant neuropsychiatric illnesses such as bipolar disorder, schizophrenia, moderate-severe anxiety, vascular dementia, Creutzfeldt-Jakob dementia, HIV dementia, and dementia in other specified diseases.

•Subjects who have been on donepezil for longer than 5 years.

•Weight> 300 pounds.

•Lactose intolerance.

•Any medical or social condition that, in the opinion of the Investigator, might pose additional risk to the participant or confound the results of the study.

•Positive Hepatitis Serology (Hep. B antigen+ or Hep. C antibody+)

Endpoints (12)

What's being measured

Protocol endpoints and posted registry outcome measures, grouped into outcome categories. Composite endpoints show their component event types. Standard codes (LOINC, SNOMED CT) are shown where available.

Coverage by outcome category

Neuroimaging

Global cognition

Function / daily living

Behavior / neuropsychiatric

Disease progression

Global cognition

2 endpoints

Secondary/protocol endpoint

Alzheimer's Disease Assessment Scale (ADAS) - Cognitive Subscale (ADAScog)

Time frame:baseline to 6 months

ADAS-Cog

event count, event

Secondary/registry result

Alzheimer's Disease Assessment Scale (ADAS) - Cognitive Subscale (ADAScog)

Time frame:baseline to 6 months

ADAS-Cog

event count, event

Posted result

Group	Value (mean), score on a scale	Standard deviation
RiluzoleBASELINEn=22 Participants	22.4981818	7.8875264
6 MONTHSn=22 Participants	21.8022727	9.7334313
PlaceboBASELINEn=20 Participants	17.9005000	7.4614719
6 MONTHSn=20 Participants	18.8495000	9.2608983

Function / daily living

2 endpoints

Secondary/protocol endpoint

ADCS Activities of Daily Living

Time frame:baseline to 6 months

ADCS-Activities of Daily Living (ADCS-ADL)

descriptive

Secondary/registry result

ADCS Activities of Daily Living

Time frame:baseline to 6 months

ADCS-Activities of Daily Living (ADCS-ADL)

descriptive

Posted result

Group	Value (mean), score on a scale	Standard deviation
RiluzoleBASELINEn=22 Participants	68.3636364	9.5096215
6 MONTHSn=22 Participants	65.5000000	11.5377228
PlaceboBASELINEn=20 Participants	68.0500000	9.3215935
6 MONTHSn=20 Participants	64.3000000	10.7757037

Behavior / neuropsychiatric

2 endpoints

Secondary/protocol endpoint

Neuropsychiatry Inventory - NPI

Time frame:baseline to 6 months

Neuropsychiatric Inventory (NPI)

descriptive

Secondary/registry result

Neuropsychiatry Inventory - NPI

Time frame:baseline to 6 months

Neuropsychiatric Inventory (NPI)

descriptive

Posted result

Group	Value (mean), score on a scale	Standard deviation
RiluzoleBASELINEn=22 Participants	9.6363636	9.1627894
6 MONTHSn=22 Participants	9.0909091	6.6254135
PlaceboBASELINEn=20 Participants	10.2000000	11.1383642
6 MONTHSn=20 Participants	14.0500000	12.8082005

Disease progression

2 endpoints

Primary/protocol endpoint

Imaging Biomarkers FDG-PET SUVR in Regions of Interest

Time frame:Change from baseline to 6 months

change from baseline, improvement

Primary/registry result

Imaging Biomarkers FDG-PET SUVR in Regions of Interest

Time frame:Change from baseline to 6 months

change from baseline, improvement

Posted result

Group	Value (mean), Standardized Uptake Value Ratios (SUVRs)	Standard deviation
PlaceboPosterior cingulaten=20 Participants	-0.048	0.035
Precuneusn=20 Participants	-0.032	0.028
Temporaln=20 Participants	-0.023	0.033
Frontaln=20 Participants	-0.129	0.066
Parietaln=20 Participants	-0.020	0.027
Hippocampusn=20 Participants	-0.018	0.034
Right Hippocampusn=20 Participants	-0.021	0.036
AD Progression scoren=20 Participants	0.579	0.607
Post Cing - Precuneusn=20 Participants	-0.041	0.042
Orbitofrontaln=20 Participants	-0.019	0.044
RiluzolePosterior cingulaten=22 Participants	-0.005	0.035
Precuneusn=22 Participants	-0.007	0.032
Temporaln=22 Participants	0.002	0.029
Frontaln=22 Participants	-0.077	0.072
Parietaln=22 Participants	-0.005	0.024
Hippocampusn=22 Participants	-0.002	0.029
Right Hippocampusn=22 Participants	0.002	0.027
AD Progression scoren=22 Participants	0.245	0.558
Post Cing - Precuneusn=22 Participants	-0.006	0.038
Orbitofrontaln=22 Participants	0.014	0.036

Neuroimaging

4 endpoints

Primary/protocol endpoint

Imaging Biomarkers N-acetylaspartate (NAA) in Posterior Cingulate (PC) Measured Through 1H MRS

Time frame:Changes from baseline to 6 months

ratio, descriptive

Primary/registry result

Imaging Biomarkers N-acetylaspartate (NAA) in Posterior Cingulate (PC) Measured Through 1H MRS

Time frame:Changes from baseline to 6 months

ratio, descriptive

Posted result

Group	Value (mean), Ratios	Standard deviation
RiluzoleBASELINE (NAA/W)n=19 Participants	0.3843874	0.0815156
3 MONTHS (NAA/W)n=19 Participants	0.3996655	0.0927727
6 MONTHS (NAA/W)n=17 Participants	0.3784181	0.0758756
BASELINE (NAA/tCr)n=19 Participants	1.4488809	0.1731644
3 MONTHS (NAA/tCr)n=19 Participants	1.4271889	0.1140340
6 MONTHS (NAA/tCr)n=17 Participants	1.4594796	0.1458860
PlaceboBASELINE (NAA/W)n=19 Participants	0.4274546	0.0684472
3 MONTHS (NAA/W)n=18 Participants	0.4248429	0.0774599
6 MONTHS (NAA/W)n=18 Participants	0.4415926	0.1039630
BASELINE (NAA/tCr)n=19 Participants	1.4802620	0.1412636
3 MONTHS (NAA/tCr)n=18 Participants	1.4766125	0.1304353
6 MONTHS (NAA/tCr)n=18 Participants	1.4811814	0.1474927

Secondary/protocol endpoint

Glutamate Levels Measured Through 1H MRS

Time frame:Change from baseline to 6 months

ratio, descriptive

Secondary/registry result

Glutamate Levels Measured Through 1H MRS

Time frame:Change from baseline to 6 months

ratio, descriptive

Posted result

Group	Value (mean), Ratios	Standard deviation
RiluzoleBASELINE (Glu/W)n=19 Participants	0.0598059	0.0164069
3 MONTHS (Glu/W)n=19 Participants	0.0579899	0.0181040
6 MONTHS (Glu/W)n=17 Participants	0.0609985	0.0156960
BASELINE (Glu/tCr)n=19 Participants	0.2280186	0.0543718
3 MONTHS (Glu/tCr)n=19 Participants	0.2080647	0.0515160
6 MONTHS (Glu/tCr)n=17 Participants	0.2339366	0.0370164
PlaceboBASELINE (Glu/W)n=19 Participants	0.0677906	0.0133271
3 MONTHS (Glu/W)n=18 Participants	0.0646162	0.0107094
6 MONTHS (Glu/W)n=18 Participants	0.0633453	0.0147764
BASELINE (Glu/tCr)n=19 Participants	0.2367567	0.0484442
3 MONTHS (Glu/tCr)n=18 Participants	0.2285644	0.0441709
6 MONTHS (Glu/tCr)n=18 Participants	0.2162526	0.0426140

Publications (1)

Bibliography

Records linked to this trial through ClinicalTrials.gov references, PubMed NCT search, and curated study seeds. 'Canonical' marks design/result papers; others are registry references or candidates.

Registry references + supporting bibliography

Matthews DC, Mao X, Dowd K, Tsakanikas D, Jiang CS, Meuser C, Andrews RD, Lukic AS, Lee J, Hampilos N, Shafiian N, Sano M, David Mozley P, Fillit H, McEwen BS, Shungu DC, Pereira AC. Riluzole, a glutamate modulator, slows cerebral glucose metabolism decline in patients with Alzheimer's disease. Brain. 2021 Dec 31;144(12):3742-3755. doi: 10.1093/brain/awab222.
PMID34145880via RESULT

Provenance

Sources

Trial identity, design, statusClinicalTrials.gov API v2

Snapshot dateJuly 21, 2026

Endpoint classificationDelfa ADRD endpoint taxonomy

Results tableClinicalTrials.gov results section

Trial facts come from public ClinicalTrials.gov records. Endpoint categories are Delfa's classification of those records, not a ClinicalTrials.gov field. All figures reflect the July 21, 2026 snapshot.