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

This study has been completed.
Sponsor:
Collaborators:
Palo Alto Institute for Research and Education, Inc
Forest Laboratories
Information provided by:
Stanford University
ClinicalTrials.gov Identifier:
NCT00255086
First received: November 15, 2005
Last updated: October 14, 2010
Last verified: October 2010
  Purpose

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 Intervention Phase
Alzheimer Disease
Drug: Memantine
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, 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

Resource links provided by NLM:


Further study details as provided by Stanford University:

Primary Outcome Measures:
  • NAA/Cr ratio [ Time Frame: 1 year ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Progression as measured by performance on the ADAS-Cog and caregiver and clinician ratings. [ Time Frame: 1 year ] [ Designated as safety issue: No ]

Enrollment: 17
Study Start Date: May 2005
Study Completion Date: February 2010
Primary Completion Date: June 2009 (Final data collection date for primary outcome measure)
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.

  Eligibility

Ages Eligible for Study:   50 Years to 95 Years
Genders Eligible for Study:   Both
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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00255086

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

Additional Information:
No publications provided

Responsible Party: Jerome A Yesavage, Stanford University School of Medicine
ClinicalTrials.gov Identifier: NCT00255086     History of Changes
Other Study ID Numbers: 95722
Study First Received: November 15, 2005
Last Updated: October 14, 2010
Health Authority: United States: Food and Drug Administration

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

ClinicalTrials.gov processed this record on August 28, 2014