Magnetic Resonance Spectroscopy Study of Memantine in Alzheimer's Disease

NCT00551161 | Completed Phase 4 Results

• 1 other identifier: NAM-MD-50
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Alzheimer Disease

Keywords

Alzheimer disease; memantine; cholinesterase inhibitors; magnetic resonance spectroscopy; N-acetylaspartate; inositol; cerebrospinal fluid; tau proteins; amyloid beta-protein

Outcome Measures

Primary Outcomes (1)

• Changes in the Metabolite Ratios of N-acetylaspartate (NAA) to Creatine (Cr), Myo-inositol (mI) to Cr, Choline (Cho) to Cr, NAA to Cho, and NAA to mI, on Cholinesterase Monotherapy vs Combination of Memantine and Cholinesterase Inhibitor

  Ratios of myo-inositol (mI), N-acetylaspartate (NAA), total creatine (Cr), and choline (Cho) by single voxel 1H MRS (proton magnetic resonance spectroscopy). Mean (± SD) metabolite levels (normalized to T2-corrected water signal intensity) and metabolite ratios for Alzheimer's disease subjects at baseline (t0), after 24 weeks of ongoing monotherapy with stable-dose cholinesterase inhibitor (t1), and after another 24 weeks of combination therapy with memantine in addition to stable-dose cholinesterase inhibitor (t2). The Wilcoxon signed-rank test was used to examine whether the change between t0 and t1 differed from the change between t1 and t2 \[(t2 - t1) - (t1 - t0)\].

  Baseline, 24 weeks, and 48 weeks

Study Arms (1)

single-arm

EXPERIMENTAL

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 20 mg per day, in addition to their ongoing stable cholinesterase inhibitor treatment

Drug: memantine

Interventions

memantine DRUG

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

Also known as: Namenda

single-arm

Eligibility Criteria

• Age: 50 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Northwell Health: lead
• Forest Laboratories: collaborator

Study Sites (1)

The Litwin-Zucker Research Center

Manhasset, New York, 11030, United States

Location

Related Publications (22)

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MeSH Terms

Conditions

Alzheimer Disease; Plaque, Amyloid

Interventions

Memantine

Condition Hierarchy (Ancestors)

Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders; Pathological Conditions, Anatomical; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Amantadine; Adamantane; Bridged-Ring Compounds; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals

Results Point of Contact

• Title: Marc L. Gordon,MD
• Organization: North Shore-LIJ Health System

MLGordon@nshs.edu

516-562-3492

Study Officials

• Marc L Gordon, M.D.

  Northwell Health

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD

Study Record Dates

• First Submitted: October 29, 2007
• First Posted: October 30, 2007
• Study Start: August 1, 2007
• Primary Completion: December 1, 2011
• Study Completion: December 1, 2011
• Last Updated: January 28, 2014
• Results First Posted: December 18, 2013

Record last verified: 2013-12

Locations

US (1)