Working... Menu

Riluzole in Mild Alzheimer's Disease

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT01703117
Recruitment Status : Recruiting
First Posted : October 10, 2012
Last Update Posted : March 18, 2019
Rockefeller University
Information provided by (Responsible Party):
Ana Pereira, Icahn School of Medicine at Mount Sinai

Brief Summary:
Cognitive aging is a major source of disability in an increasingly aging population. The paucity of effective treatments for cognitive aging disorders, and most importantly in Alzheimer's disease instigates a need for further research into novel therapeutic possibilities. Alzheimer's disease is the most common neurodegenerative disorder and its prevalence steeply increases. Glutamate-mediated excitotoxicity in neuropsychiatric disorders and in particular in Alzheimer's disease has been shown to cause significant cerebral damage. Early effective therapeutic intervention in Alzheimer's disease is critical in order to prevent or at least slow down neuropathological progression that will lead to widespread irreversible neuronal loss and significant cognitive dysfunction. Riluzole, a glutamate modulator agent, will be tested in mild Alzheimer's disease patients. Cognitive functional changes along with two established in vivo biomarkers, namely, Magnetic Resonance Spectroscopy (MRS) and Fluorodeoxyglucose (18F) positron emission tomography (FDG-PET) will be evaluated.

Condition or disease Intervention/treatment Phase
Alzheimer's Disease Drug: Riluzole Drug: Placebo Phase 2

Detailed Description:
A double-blinded, randomized, placebo-controlled study will be performed. Forty-eight individuals with a diagnosis of mild Alzheimer's disease between 50-95 years old will complete the study. All forty-eight individuals will have been on an acetylcholinesterase inhibitor, which is FDA approved for the treatment of Alzheimer's disease, for at least 2 months prior to initiating the study, unless the medication was not previously tolerated. Twenty-four mild Alzheimer's disease patients will receive riluzole and another 24 will receive a placebo. All patients will have a neurological evaluation and neuropsychological tests performed to confirm that they meet criteria for probable Alzheimer's disease set out by the National Institute on Aging - Alzheimer's disease Association that recently revisited the NINCDS-ADRDA criteria along with FDG-PET biomarker consistent with Alzheimer's disease.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 48 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: Glutamatergic Dysfunction in Cognitive Aging: Riluzole in Mild Alzheimer's Disease
Actual Study Start Date : November 2013
Estimated Primary Completion Date : November 2020
Estimated Study Completion Date : November 2020

Resource links provided by the National Library of Medicine

Drug Information available for: Riluzole

Arm Intervention/treatment
Experimental: age matched cohort 50-95 years old
24 subjects between the ages of 50-95 will receive riluzole
Drug: Riluzole
24 subjects between the ages of 60-85 will receive study drug.
Other Name: no other names

Placebo Comparator: 24 subjects between 50-95 years old
24 subjects between 50-95 will receive placebo
Drug: Placebo
24 subjects between the ages of 60-85 will receive placebo
Other Name: no other names

Primary Outcome Measures :
  1. Imaging Biomarkers N-acetylaspartate (NAA) and FDG-PET values in regions of interest [ Time Frame: Change from baseline at 6 months ]
    To determine if after administration of the drug riluzole over 6 months, patients with mild Alzheimer's disease will have changes in regions of interest, less decline in the levels of N-acetylaspartate (NAA), a neuronal viability marker (obtained through Magnetic Resonance Spectroscopy-MRS) in comparison to the control group, and a less prominent decline in cerebral metabolism in the regions of interest affected in mild Alzheimer's disease in FDG-PET as compared to the control group.

Secondary Outcome Measures :
  1. Cognitive function (neuropsychological tests); Glutamate levels obtained through MRS [ Time Frame: Change from baseline at 3 and 6 months ]

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

Layout table for eligibility information
Ages Eligible for Study:   50 Years to 95 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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+)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01703117

Layout table for location contacts
Contact: Ana Pereira, MD 212 241-6984

Layout table for location information
United States, New York
Icahn School of Medicine at Mount Sinai Recruiting
New York, New York, United States, 10029
Contact: Ana Pereira, MD   
The Rockefeller University Recruiting
New York, New York, United States, 10065
Contact: RU Cares    800-782-2737   
Sponsors and Collaborators
Icahn School of Medicine at Mount Sinai
Rockefeller University
Layout table for investigator information
Principal Investigator: Ana Pereira, MD Icahn School of Medicine at Mount Sinai

Layout table for additonal information
Responsible Party: Ana Pereira, Principal Investigator; Assistant Professor of Neurology and Neuroscience, Icahn School of Medicine at Mount Sinai Identifier: NCT01703117     History of Changes
Other Study ID Numbers: GCO 18-0623
APE-0792 ( Other Identifier: Rockefeller University )
First Posted: October 10, 2012    Key Record Dates
Last Update Posted: March 18, 2019
Last Verified: February 2019

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes

Keywords provided by Ana Pereira, Icahn School of Medicine at Mount Sinai:
Alzheimer's Disease

Additional relevant MeSH terms:
Layout table for MeSH terms
Alzheimer Disease
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Neurodegenerative Diseases
Neurocognitive Disorders
Mental Disorders
Excitatory Amino Acid Antagonists
Excitatory Amino Acid Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Neuroprotective Agents
Protective Agents