Riluzole in Mild Alzheimer's Disease
Condition: Alzheimer's Disease
MeSH terms: Alzheimer Disease
Intervention: Riluzole; Placebo
Intervention description: 20-22 subjects between the ages of 60-85 will receive study drug.; 20-22 subjects between the ages of 60-85 will receive placebo
Intervention MeSH terms: Riluzole
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 50.0
Sex: All
Minimum age: 50 Years
Maximum age: 95 Years
Healthy volunteers: No
Keywords: Alzheimer's Disease; Dementia

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.
    

Eligibility criteria:

        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+)