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

Alzheimer Disease Clinical Trial

Official title:

The Effect of Memantine on Brain Structure and Chemistry in Alzheimer's Disease Patients: A Randomized, Placebo-Controlled, 52-Week Clinical Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00255086
• Other study ID #: 95722
• Status: Completed
• Phase: Phase 3
• First received: November 15, 2005
• Last updated: October 14, 2010
• Start date: May 2005
• Est. completion date: February 2010

Study information

• Verified date: October 2010
• Source: Stanford University
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 17
• Est. completion date: February 2010
• Est. primary completion date: June 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 50 Years to 95 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Pharmacokinetics/Dynamics Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Alzheimer Disease

Intervention

Drug:
• Memantine

Locations

Country	Name	City	State
United States	VA Palo Alto Health Care System	Palo Alto	California

Sponsors (3)

Lead Sponsor	Collaborator
Stanford University	Forest Laboratories, Palo Alto Veterans Institute for Research

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	NAA/Cr ratio		1 year	No
Secondary	Progression as measured by performance on the ADAS-Cog and caregiver and clinician ratings.		1 year	No

External Links

•   Click here for more information about the Stanford/VA Aging Clinical Research Center