Magnetic Resonance Spectroscopy Study of Memantine in Alzheimer's Disease
Condition: Alzheimer Disease
MeSH terms: Alzheimer Disease
Intervention: memantine
Intervention description: 24-week observational lead-in period, wherein patients already on a stable dose of donepezil, rivastigmine, or galantamine continue on that dose, followed by a 24-week open-label memantine period, wherein patients receive open-label memantine treatment titrated to a dose of 10 mg orally b.i.d., in addition to their ongoing stable cholinesterase inhibitor treatment
Intervention MeSH terms: Memantine
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 12.0
Sex: All
Minimum age: 50 Years
Healthy volunteers: No
Keywords: Alzheimer disease; memantine; cholinesterase inhibitors; magnetic resonance spectroscopy; N-acetylaspartate; inositol; cerebrospinal fluid; tau proteins; amyloid beta-protein

Summary:

      We are studying subjects with mild to moderate Alzheimer's disease who have been on a stable
      dose of any cholinesterase inhibitor [donepezil (Aricept), rivastigmine (Exelon), or
      galantamine (Razadyne)] for at least 3 months, and have not previously taken memantine
      (Namenda). This is an open-label study, with magnetic resonance spectroscopy (MRS) as the
      primary outcome measure, along with neuropsychological testing, and optional lumbar puncture,
      evaluating patients on their stable dose of a cholinesterase inhibitor over 24 weeks,
      followed by another 24 weeks on memantine in combination with stable dose of cholinesterase
      inhibitor. The purpose of this study is to characterize the progression of disease using MRS,
      cerebrospinal fluid (CSF) biomarkers, and cognitive outcome measures, and to determine
      whether changes in cognitive function on neuropsychological testing are correlated to changes
      in MR spectroscopic and/or CSF biomarkers.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Written informed consent must be obtained from either the subject (if they have
             decisional capacity) or a Legally Authorized Representative (LAR) (as required by
             state or local law and the IRB), prior to the initiation of any study-specific
             procedures. (If a subject is unable to fully consent for himself/herself, but has
             capacity to appoint a research proxy, the legally authorized research proxy will be
             asked to sign consent, with the subject signing assent.)

          -  Male or female outpatients at least 50 years of age at Screening.

          -  If female, the patient must be at least two years postmenopausal or surgically sterile
             at Screening.

          -  The patient has a current diagnosis of probable Alzheimer's disease consistent with
             NINCDS-ADRDA criteria.

          -  The patient has a knowledgeable and reliable caregiver who will accompany the patient
             to all clinic visits during the course of the study.

          -  Mini-Mental State Examination (MMSE) score of at least 15 and not greater than 26 at
             Screening.

          -  Ongoing therapy with a stable dose of donepezil, rivastigmine, or galantamine for at
             least three months at the time of Screening.

          -  Physical examination, laboratory evaluations, and EKG results at Screening must be
             normal, or abnormal findings must be judged not clinically significant by the
             Investigator.

          -  The patient's MRI scan conducted as part of Screening (Visit 1) must be consistent
             with a diagnosis of Alzheimer's disease, and must not include any findings that could
             confound the spectroscopic analysis of subsequent MRIs (e.g., large cortical stroke,
             tumor, or other space-occupying brain lesions).

          -  Vision and hearing (hearing aid permissible) must be sufficient for compliance with
             testing procedures.

          -  The patient and/or their Legally Authorized Representative, and their caregiver must
             be able to speak, read, and understand English sufficiently to understand the nature
             of the study, to provide written informed consent, and to allow completion of all
             study assessments.

        Exclusion Criteria:

          -  Clinically significant vitamin B12 deficiency at Screening.

          -  Patients with a modified Hachinski ischemia score greater than 4 at Screening.

          -  Patients with evidence of clinically significant and active pulmonary,
             gastrointestinal, renal, hepatic, endocrine, or cardiovascular system disease.
             Patients with controlled hypertension and right bundle branch block (complete or
             partial) may be included in the study. Patients with thyroid disease may also be
             included in the study provided they are euthyroid on treatment. Patients with
             controlled diabetes may also be included.

          -  Patients with severe renal impairment (estimated creatinine clearance < 35 mL/min).

          -  Patients with systolic blood pressure (while sitting) greater then than 180 mm Hg or
             less then 90 mm Hg, or diastolic blood pressure (while sitting) greater than 100 mm Hg
             or less than 50 mm Hg at Screening.

          -  Patients with evidence of other neurological disorders including, but not limited to,
             stroke, Parkinson's disease, seizure disorder, hydrocephalus, or head injury with loss
             of consciousness within the past five years at Screening.

          -  Patients with a current DSM-IV Axis I disorder other than Alzheimer's disease,
             including schizophrenia or schizoaffective disorder, bipolar disorder, current major
             depressive episode, psychosis, panic disorder, or post-traumatic stress disorder.

          -  Patients with dementia complicated by other organic disease.

          -  Patients who have had a previous brain scan (MRI or CT) with results inconsistent with
             a diagnosis of probable Alzheimer's disease.

          -  Patients with an oncological diagnosis (hematological or solid tumor) which is
             currently being treated, or for which there has been treatment within the year
             preceding Screening, or for which there is still evidence of active disease. (Note:
             Patients with local dermatological tumors at such as basal or squamous cell carcinoma
             may be included.)

          -  Patients with an object in the head or neck which would invalidate or obstruct the
             successful completion of an MRI scan, or patients who have other contraindications to
             MRI, including those with implanted ferromagnetic material or devices such as cardiac
             pacemakers, deep brain stimulators, cochlear implants, or intraocular metallic shards.

          -  Patients who are claustrophobic and/or unable to tolerate MRI at Screening, or whom
             the Investigator believes will not be able to tolerate further scans scheduled during
             the course of the study.

          -  Patients with a known or suspected history (within the past 5 years at Screening) of
             alcoholism or drug abuse.

          -  Patients who are on an unstable dose of a cholinesterase inhibitor (donepezil,
             rivastigmine, or galantamine), are currently taking more than one cholinesterase
             inhibitor at Screening, who are likely to require a change in cholinesterase drug dose
             during the course of the study, or for whom a cholinesterase inhibitor therapy is
             contraindicated.

          -  Patients with a history of severe drug allergy or hypersensitivity, or patients with
             known hypersensitivity to memantine, amantadine, rimantadine, or lactose.

          -  Patients who have been previously treated with or have participated in an
             investigational study of neramexane, memantine, or amantadine.

          -  Patients previously treated with commercial memantine.

          -  Patients who have been in an investigational drug study or who have received treatment
             with an investigational drug within 30 days or 5 half-lives (whichever is longer) of
             Screening.

          -  Patients or caregivers who are unwilling or unable to abide by the visit schedule and
             other requirements of the study.

          -  Any condition which would make the patient or caregiver unsuitable for the study in
             the opinion of the Investigator.