- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01703117
Riluzole in Mild Alzheimer's Disease
Glutamatergic Dysfunction in Cognitive Aging: Riluzole in Mild Alzheimer's Disease
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
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New York
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New York, New York, United States, 10029
- Icahn School of Medicine at Mount Sinai
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New York, New York, United States, 10065
- The Rockefeller University
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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+)
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Double
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Experimental: age matched cohort 50-95 years old
20-22 subjects between the ages of 50-95 will receive riluzole
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20-22 subjects between the ages of 60-85 will receive study drug.
Other Names:
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Placebo Comparator: 24 subjects between 50-95 years old
20-22 subjects between 50-95 will receive placebo
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20-22 subjects between the ages of 60-85 will receive placebo
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Imaging Biomarkers FDG-PET SUVR in Regions of Interest
Time Frame: Change from baseline to 6 months
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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. |
Change from baseline to 6 months
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Imaging Biomarkers N-acetylaspartate (NAA) in Posterior Cingulate (PC) Measured Through 1H MRS
Time Frame: Changes from baseline to 6 months
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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.
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Changes from baseline to 6 months
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Glutamate Levels Measured Through 1H MRS
Time Frame: Change from baseline to 6 months
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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.
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Change from baseline to 6 months
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Alzheimer's Disease Assessment Scale (ADAS) - Cognitive Subscale (ADAScog)
Time Frame: baseline to 6 months
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The 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.
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baseline to 6 months
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Neuropsychiatry Inventory - NPI
Time Frame: baseline to 6 months
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NPI 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 |
baseline to 6 months
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ADCS Activities of Daily Living
Time Frame: baseline to 6 months
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ADCS-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 |
baseline to 6 months
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Collaborators and Investigators
Collaborators
Investigators
- Principal Investigator: Ana Pereira, MD, Icahn School of Medicine at Mount Sinai
Publications and helpful links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Mental Disorders
- Brain Diseases
- Central Nervous System Diseases
- Nervous System Diseases
- Neurocognitive Disorders
- Neurodegenerative Diseases
- Dementia
- Tauopathies
- Alzheimer Disease
- Physiological Effects of Drugs
- Neurotransmitter Agents
- Molecular Mechanisms of Pharmacological Action
- Excitatory Amino Acid Antagonists
- Excitatory Amino Acid Agents
- Neuroprotective Agents
- Protective Agents
- Anticonvulsants
- Riluzole
Other Study ID Numbers
- GCO 18-0623
- APE-0792 (Other Identifier: Rockefeller University)
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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