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The Effect of Memantine on Brain Structure and Chemistry in Alzheimer's Disease Patients

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ClinicalTrials.gov Identifier: NCT00255086
Recruitment Status : Completed
First Posted : November 17, 2005
Results First Posted : April 7, 2017
Last Update Posted : April 7, 2017
Sponsor:
Collaborators:
Information provided by (Responsible Party):

Study Description
Brief Summary:
The aim of the proposed study is to determine if the NMDA receptor antagonist memantine has a neuroprotective effect on magnetic resonance spectroscopic imaging (MRS) measures of brain NAA and magnetic resonance imaging (MRI) volumetric measures of hippocampal volume. In secondary analyses, we will determine if measures of clinical stabilization produced by memantine in the treatment of Alzheimer's disease (AD) parallels stabilization of MRS measures of brain NAA and MRI volumetric measures of hippocampal volume.

Condition or disease Intervention/treatment Phase
Alzheimer Disease Drug: Memantine Drug: Placebo pill Phase 3

Detailed Description:

Alzheimer's disease (AD) is the most common form of dementia. Currently, there are more than 4 million individuals with dementia in the United States with at least 400,000 deaths annually. AD is a progressive, neurodegenerative disorder, characterized neuropathologically by widespread neuronal loss, presence of neurofibrillary tangles, and deposits of beta amyloid in cerebral blood vessels and neuritic plaques. Since the medial-temporal lobes, hippocampus, and association cortex are significantly impacted it is not surprising that the primary symptom of AD is a decline in cognitive functioning that leads to marked impairment in daily functioning. In particular, memory impairments, visuospatial decline, language difficulties, and loss of executive function are central cognitive symptoms of this illness. Behavioral disturbances such as agitation and hallucinations often accompany disease progression. The illness lasts approximately 7 to 10 years, with patients requiring total care in the latter stages. Thus, AD places a tremendous emotional and economic burden on both patients and their caregivers. Beyond a cure, therapeutic approaches which would alleviate the symptoms or delay progression could be of substantial psychological and economic benefit. Recent placebo controlled clinical trials have shown memantine to be efficacious in the treatment of patients with moderate to severe AD.

The aim of the proposed study is to determine if the NMDA receptor antagonist memantine has a neuroprotective effect on magnetic resonance spectroscopic imaging (MRS) measures of brain NAA and magnetic resonance imaging (MRI) volumetric measures of hippocampal volume. In secondary analyses, we will determine if measures of clinical stabilization produced by memantine in the treatment of Alzheimer's disease (AD) parallels stabilization of MRS measures of brain NAA and MRI volumetric measures of hippocampal volume.


Study Design

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 17 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: The Effect of Memantine on Brain Structure and Chemistry in Alzheimer's Disease Patients: A Randomized, Placebo-Controlled, 52-Week Clinical Trial
Study Start Date : May 2005
Primary Completion Date : June 2009
Study Completion Date : February 2010


Arms and Interventions

Arm Intervention/treatment
Experimental: Memantine
10mg Memantine
Drug: Memantine
10mg Memantine
Other Name: Namenda
Placebo Comparator: Control
10 mg Placebo pill
Drug: Placebo pill
10mg placebo pill
Other Name: placebo


Outcome Measures

Primary Outcome Measures :
  1. NAA/Cr Ratio [ Time Frame: Baseline; Year 1 ]
    To determine if memantine has a neuroprotective effect on magnetic resonance spectroscopic imaging (MRS) measures of hippocampal n-acetyl aspartate (NAA) and magnetic resonance imaging volumetric measures (MRI) of hippocampal volume.


Secondary Outcome Measures :
  1. Mean Change on the ADAS-Cog Score After 1 Year [ Time Frame: Baseline; Year 1 ]
    Progression of cognitive functioning as measured by performance on the Alzheimer's Disease (AD) Assessment Scale-cognitive subscale (ADAS-Cog). ADAS-cog is the most popular cognitive testing instrument used in clinical trials of nootropics, and measures disturbances of of memory, language, praxis, attention and other cognitive abilities which are often referred to as the core symptoms of AD. Responses are summed for an overall score which can range from 0-70. The greater the dysfunction, the higher the score. A typical score for a person without dementia is 5.


Eligibility Criteria

Information from the National Library of Medicine

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Ages Eligible for Study:   50 Years to 95 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:1. Dementia criteria by DSM-IV.

2. 50-95 years of age inclusive.

3. MMSE at screen and baseline 7-28 inclusive.

4. Conversant in English.

5. Caregiver/study partner willing to participate, supervise the patient and be available for administration of study medication.

6. Able to ingest oral medication.

Exclusion Criteria:1. History of clinically significant stroke without substantial recovery.

2. Neurological or medical conditions causing significant disability independent of dementia.

3. Parkinson's disease.

4. History in past two years of focal brain lesion, head injury with loss of consciousness or DSM-IV criteria for any major psychiatric disorder including psychosis, major depression, bipolar disorder, alcohol or substance abuse.

5. Dementia due to Korsakoff's syndrome or infectious diseases such as Creutzfeldt-Jakob disease, herpes, encephalitis, or human immunodeficiency virus.

6. Sensory impairment that would prevent subject from participating in or cooperating with the protocol.

7. Significant clinical disorder or laboratory finding that renders the subject unsuitable for receiving an investigational drug including: clinically significant or unstable hematologic, hepatic, cardiovascular, pulmonary, gastrointestinal, endocrine, metabolic, renal, or other systemic disease or laboratory abnormality.

8. Clinical contraindication to the use of memantine (e.g., hypersensitivity).

9. History of seizure within past 5 years prior to screening.

10. Platelet count < 100,000/mm3.

11. History of claustrophobia

12. Presence of metallic implants such as pacemakers, surgical aneurysm clips, or known metal fragments embedded in the body

Contacts and Locations

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 ClinicalTrials.gov identifier (NCT number): NCT00255086


Locations
United States, California
VA Palo Alto Health Care System
Palo Alto, California, United States, 94304
Sponsors and Collaborators
Stanford University
Palo Alto Veterans Institute for Research
Forest Laboratories
Investigators
Study Director: J. Wesson Ashford Jr., MD, PhD Stanford University
Principal Investigator: Jerome A Yesavage Stanford University
More Information

Responsible Party: Jerome A Yesavage,, Principle Investigator, Stanford University
ClinicalTrials.gov Identifier: NCT00255086     History of Changes
Other Study ID Numbers: 95722
First Posted: November 17, 2005    Key Record Dates
Results First Posted: April 7, 2017
Last Update Posted: April 7, 2017
Last Verified: February 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Additional relevant MeSH terms:
Alzheimer Disease
Dementia
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Tauopathies
Neurodegenerative Diseases
Neurocognitive Disorders
Mental Disorders
Memantine
Antiparkinson Agents
Anti-Dyskinesia Agents
Dopamine Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Excitatory Amino Acid Antagonists
Excitatory Amino Acid Agents