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Riluzole in Mild Alzheimer's Disease

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ClinicalTrials.gov Identifier: NCT01703117
Recruitment Status : Recruiting
First Posted : October 10, 2012
Last Update Posted : March 18, 2019
Sponsor:
Collaborator:
Rockefeller University
Information provided by (Responsible Party):
Ana Pereira, Icahn School of Medicine at Mount Sinai

Tracking Information
First Submitted Date  ICMJE October 4, 2012
First Posted Date  ICMJE October 10, 2012
Last Update Posted Date March 18, 2019
Actual Study Start Date  ICMJE November 2013
Estimated Primary Completion Date November 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 21, 2017)
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.
Original Primary Outcome Measures  ICMJE
 (submitted: October 5, 2012)
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 in the hippocampus and prefrontal cortex, 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.
Change History Complete list of historical versions of study NCT01703117 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: October 5, 2012)
Cognitive function (neuropsychological tests); Glutamate levels obtained through MRS [ Time Frame: Change from baseline at 3 and 6 months ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Riluzole in Mild Alzheimer's Disease
Official Title  ICMJE Glutamatergic Dysfunction in Cognitive Aging: Riluzole in Mild Alzheimer's Disease
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.
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Condition  ICMJE Alzheimer's Disease
Intervention  ICMJE
  • Drug: Riluzole
    24 subjects between the ages of 60-85 will receive study drug.
    Other Name: no other names
  • Drug: Placebo
    24 subjects between the ages of 60-85 will receive placebo
    Other Name: no other names
Study Arms  ICMJE
  • Experimental: age matched cohort 50-95 years old
    24 subjects between the ages of 50-95 will receive riluzole
    Intervention: Drug: Riluzole
  • Placebo Comparator: 24 subjects between 50-95 years old
    24 subjects between 50-95 will receive placebo
    Intervention: Drug: Placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: October 5, 2012)
48
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE November 2020
Estimated Primary Completion Date November 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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+)
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 50 Years to 95 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Ana Pereira, MD 212 241-6984 ana.pereira@mssm.edu
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01703117
Other Study ID Numbers  ICMJE GCO 18-0623
APE-0792 ( Other Identifier: Rockefeller University )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Ana Pereira, Icahn School of Medicine at Mount Sinai
Study Sponsor  ICMJE Icahn School of Medicine at Mount Sinai
Collaborators  ICMJE Rockefeller University
Investigators  ICMJE
Principal Investigator: Ana Pereira, MD Icahn School of Medicine at Mount Sinai
PRS Account Icahn School of Medicine at Mount Sinai
Verification Date February 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP