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VITAL - VITamins to Slow ALzheimer's Disease (Homocysteine Study)

Phase 3
Completed
Conditions
Alzheimer's Disease
Registration Number
NCT00056225
Lead Sponsor
National Institute on Aging (NIA)
Brief Summary

The purpose of this study is to determine whether reduction of homocysteine levels with high-dose folate (folic acid), B6, and B12 supplementation will slow the rate of cognitive decline in persons with Alzheimer's disease.

Detailed Description

Blood levels of homocysteine are elevated in Alzheimer's disease (AD), and hyperhomocysteinemia may contribute to disease pathophysiology by vascular and direct neurotoxic mechanisms. Homocysteine levels can be reduced by administration of high dose supplements of folate (folic acid) and vitamins B6 and B12. The proposed study is for a multicenter, randomized, controlled clinical trial to determine whether reduction of homocysteine levels with high-dose folate/B6/B12 supplementation will slow the rate of cognitive decline in subjects with AD.

This will be a parallel design study, including two groups of unequal size: 60% of subjects will receive daily high-dose supplements (folate 5mg, vitamin B6 25mg, vitamin B12 1 mg), and 40% will receive an identical looking placebo. The duration of treatment will be 18 months, and participants will make eight visits to the assigned study site for safety and efficacy assessments of the medications. The primary outcome measure will be the longitudinal decline in the ADAScog, a psychometric instrument that evaluates memory, attention, reasoning, language, orientation and praxis (Rosen et al 1984). To power the trial to detect a 25% reduction in rate of ADAScog decline (80% power, alpha=0.05, drop-out estimate 20%, drop-in estimate 10%), it will enroll a total of 400 participants. Persons of minority racial groups are also being recruited, although all participants must be able to speak either English or Spanish.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
340
Inclusion Criteria
  • National Institute of Neurological Disorders and Stroke (NINDS)/Alzheimer's Disease and Related Disorders Association (ADRDA) criteria for probable Alzheimer's disease.
  • Mini-Mental Status Examination (MMSE) score between 14 and 26, inclusive
  • Stable medical condition for 3 months
  • Stable medications for 4 weeks prior to the screening visit
  • Physically acceptable for this study as confirmed by medical history, physical exam, neurologic exam and clinical laboratory tests
  • Supervision available for administration of study medications
  • Study partner to accompany subject to all scheduled visits
  • Fluent in English or Spanish
  • Modified Hachinski equal to or less than 4 CT or magnetic resonance imaging (MRI) since onset of memory impairment demonstrating absence of clinically significant focal lesion
  • Able to complete baseline assessments
  • 6 years of education or work history sufficient to exclude mental retardation
  • Able to ingest oral medication
Exclusion Criteria
  • B12 or folate deficiency
  • Renal insufficiency (serum creatinine >=2.0)
  • Active neoplastic disease (skin tumors other than melanoma are not exclusionary; patients with stable prostate cancer may be included at the discretion of the project director)
  • Use of another investigational agent within 2 months
  • History of clinically significant stroke
  • Current evidence or history in the past 2 years of epilepsy, focal brain lesion, head injury with loss of consciousness and/or immediate confusion after the injury, or DSM-IV criteria for any major psychiatric disorder including psychosis, major depression, bipolar disorder, alcohol or substance abuse
  • Blindness, deafness, language difficulties or any other disability which may prevent the subject from participating or cooperating in the protocol

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Primary Outcome Measures
NameTimeMethod
Secondary Outcome Measures
NameTimeMethod

Trial Locations

Locations (38)

Georgetown University

🇺🇸

Washington, DC, District of Columbia, United States

Mayo Clinic, Scottsdale

🇺🇸

Scottsdale, Arizona, United States

Southern Illinois University

🇺🇸

Springfield, Illinois, United States

ClinSearch

🇺🇸

Kenilworth, New Jersey, United States

Sun Health Research Institute

🇺🇸

Sun City, Arizona, United States

University of Arizona, Arizona Health Sciences Center

🇺🇸

Tucson, Arizona, United States

Memorial Hospital of Rhode Island, Alzheimer's Disease and Memory Disorder Clinic

🇺🇸

Pawtucket, Rhode Island, United States

Mayo Clinic

🇺🇸

Jacksonville, Florida, United States

University of California, San Diego

🇺🇸

La Jolla, California, United States

Howard University

🇺🇸

Washington, DC, District of Columbia, United States

New York University Medical Center

🇺🇸

New York, New York, United States

Mt. Sinai School of Medicine

🇺🇸

New York, New York, United States

Columbia University

🇺🇸

New York, New York, United States

Stanford University

🇺🇸

Palo Alto, California, United States

University of Rochester Medical Center, Alzheimer's Disease Center

🇺🇸

Rochester, New York, United States

University of California, Los Angeles

🇺🇸

Los Angeles, California, United States

University of Alabama

🇺🇸

Birmingham, Alabama, United States

University of California, Irvine, Institute for Brain Aging and Dementia

🇺🇸

Irvine, California, United States

University of California, Davis

🇺🇸

Sacramento, California, United States

University of Southern California

🇺🇸

Los Angeles, California, United States

Yale University

🇺🇸

New Haven, Connecticut, United States

University of South Florida

🇺🇸

Tampa, Florida, United States

Emory University

🇺🇸

Atlanta, Georgia, United States

Northwestern University

🇺🇸

Chicago, Illinois, United States

Rush Presbyterian/St. Lukes Medical Center, Rush Alzheimer's Disease Center

🇺🇸

Chicago, Illinois, United States

Indiana University

🇺🇸

Indianapolis, Indiana, United States

Brigham and Women's Hospital

🇺🇸

Boston, Massachusetts, United States

Boston University School of Medicine

🇺🇸

Boston, Massachusetts, United States

University of Michigan

🇺🇸

Ann Arbor, Michigan, United States

University of Nevada School of Medicine, Center for Cognitive Aging

🇺🇸

Las Vegas, Nevada, United States

University Memory and Aging Center, Case Western Reserve University/University Hospitals of Cleveland

🇺🇸

Cleveland, Ohio, United States

Oregon Health and Science University, Oregon Aging and Alzheimer's Disease Center

🇺🇸

Portland, Oregon, United States

University of Pennsylvania

🇺🇸

Philadelphia, Pennsylvania, United States

University of Pittsburgh

🇺🇸

Pittsburgh, Pennsylvania, United States

Medical University of South Carolina

🇺🇸

North Charleston, South Carolina, United States

University of Texas, Southwestern Medical Center

🇺🇸

Dallas, Texas, United States

Baylor College of Medicine

🇺🇸

Houston, Texas, United States

University of Washington

🇺🇸

Seattle, Washington, United States

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