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

NCT ID: NCT00056225

Last Updated: 2009-06-12

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

340 participants

Study Classification

INTERVENTIONAL

Study Start Date

2003-01-31

Study Completion Date

2007-06-30

Brief Summary

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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

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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.

Conditions

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Alzheimer's Disease

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Interventions

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Folate

Intervention Type DRUG

Vitamin B6

Intervention Type DRUG

Vitamin B12

Intervention Type DRUG

Eligibility Criteria

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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
Minimum Eligible Age

55 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Alzheimer's Disease Cooperative Study (ADCS)

OTHER

Sponsor Role collaborator

National Institute on Aging (NIA)

NIH

Sponsor Role lead

Principal Investigators

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Paul Aisen, MD

Role: PRINCIPAL_INVESTIGATOR

Georgetown University, Department of Neurology

Locations

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University of Alabama

Birmingham, Alabama, United States

Site Status

Mayo Clinic, Scottsdale

Scottsdale, Arizona, United States

Site Status

Sun Health Research Institute

Sun City, Arizona, United States

Site Status

University of Arizona, Arizona Health Sciences Center

Tucson, Arizona, United States

Site Status

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

Irvine, California, United States

Site Status

University of California, San Diego

La Jolla, California, United States

Site Status

University of Southern California

Los Angeles, California, United States

Site Status

University of California, Los Angeles

Los Angeles, California, United States

Site Status

Stanford University

Palo Alto, California, United States

Site Status

University of California, Davis

Sacramento, California, United States

Site Status

Yale University

New Haven, Connecticut, United States

Site Status

Georgetown University

Washington D.C., District of Columbia, United States

Site Status

Howard University

Washington D.C., District of Columbia, United States

Site Status

Mayo Clinic

Jacksonville, Florida, United States

Site Status

University of South Florida

Tampa, Florida, United States

Site Status

Emory University

Atlanta, Georgia, United States

Site Status

Northwestern University

Chicago, Illinois, United States

Site Status

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

Chicago, Illinois, United States

Site Status

Southern Illinois University

Springfield, Illinois, United States

Site Status

Indiana University

Indianapolis, Indiana, United States

Site Status

Brigham and Women's Hospital

Boston, Massachusetts, United States

Site Status

Boston University School of Medicine

Boston, Massachusetts, United States

Site Status

University of Michigan

Ann Arbor, Michigan, United States

Site Status

University of Nevada School of Medicine, Center for Cognitive Aging

Las Vegas, Nevada, United States

Site Status

ClinSearch

Kenilworth, New Jersey, United States

Site Status

New York University Medical Center

New York, New York, United States

Site Status

Mt. Sinai School of Medicine

New York, New York, United States

Site Status

Columbia University

New York, New York, United States

Site Status

University of Rochester Medical Center, Alzheimer's Disease Center

Rochester, New York, United States

Site Status

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

Cleveland, Ohio, United States

Site Status

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

Portland, Oregon, United States

Site Status

University of Pennsylvania

Philadelphia, Pennsylvania, United States

Site Status

University of Pittsburgh

Pittsburgh, Pennsylvania, United States

Site Status

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

Pawtucket, Rhode Island, United States

Site Status

Medical University of South Carolina

North Charleston, South Carolina, United States

Site Status

University of Texas, Southwestern Medical Center

Dallas, Texas, United States

Site Status

Baylor College of Medicine

Houston, Texas, United States

Site Status

University of Washington

Seattle, Washington, United States

Site Status

Countries

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United States

References

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Seshadri S, Beiser A, Selhub J, Jacques PF, Rosenberg IH, D'Agostino RB, Wilson PW, Wolf PA. Plasma homocysteine as a risk factor for dementia and Alzheimer's disease. N Engl J Med. 2002 Feb 14;346(7):476-83. doi: 10.1056/NEJMoa011613.

Reference Type BACKGROUND
PMID: 11844848 (View on PubMed)

Aisen PS, Egelko S, Andrews H, Diaz-Arrastia R, Weiner M, DeCarli C, Jagust W, Miller JW, Green R, Bell K, Sano M. A pilot study of vitamins to lower plasma homocysteine levels in Alzheimer disease. Am J Geriatr Psychiatry. 2003 Mar-Apr;11(2):246-9.

Reference Type BACKGROUND
PMID: 12611755 (View on PubMed)

Kruman II, Kumaravel TS, Lohani A, Pedersen WA, Cutler RG, Kruman Y, Haughey N, Lee J, Evans M, Mattson MP. Folic acid deficiency and homocysteine impair DNA repair in hippocampal neurons and sensitize them to amyloid toxicity in experimental models of Alzheimer's disease. J Neurosci. 2002 Mar 1;22(5):1752-62. doi: 10.1523/JNEUROSCI.22-05-01752.2002.

Reference Type BACKGROUND
PMID: 11880504 (View on PubMed)

Aisen PS, Schneider LS, Sano M, Diaz-Arrastia R, van Dyck CH, Weiner MF, Bottiglieri T, Jin S, Stokes KT, Thomas RG, Thal LJ; Alzheimer Disease Cooperative Study. High-dose B vitamin supplementation and cognitive decline in Alzheimer disease: a randomized controlled trial. JAMA. 2008 Oct 15;300(15):1774-83. doi: 10.1001/jama.300.15.1774.

Reference Type RESULT
PMID: 18854539 (View on PubMed)

Other Identifiers

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IA0041

Identifier Type: -

Identifier Source: org_study_id

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