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

National Institute on Aging (NIA) (NIH)
Overall Status
Completed ID
Alzheimer's Disease Cooperative Study (ADCS) (Other)

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
Phase 3

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.

Study Design

Study Type:
Actual Enrollment :
340 participants
Intervention Model:
Parallel Assignment
Primary Purpose:
Official Title:
High Dose Supplements to Reduce Homocysteine and Slow the Rate of Cognitive Decline in Alzheimer's Disease (Vitamins to Slow Alzheimer's - VITAL)
Study Start Date :
Jan 1, 2003
Actual Primary Completion Date :
Jun 1, 2007
Actual Study Completion Date :
Jun 1, 2007

Outcome Measures

Primary Outcome Measures

    Eligibility Criteria


    Ages Eligible for Study:
    55 Years and Older
    Sexes Eligible for Study:
    Accepts Healthy Volunteers:
    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

    Contacts and Locations


    Site City State Country Postal Code
    1 University of Alabama Birmingham Alabama United States 35294
    2 Mayo Clinic, Scottsdale Scottsdale Arizona United States 85259
    3 Sun Health Research Institute Sun City Arizona United States 85351
    4 University of Arizona, Arizona Health Sciences Center Tucson Arizona United States 85724
    5 University of California, Irvine, Institute for Brain Aging and Dementia Irvine California United States 92697
    6 University of California, San Diego La Jolla California United States 92093-0624
    7 University of Southern California Los Angeles California United States 90033
    8 University of California, Los Angeles Los Angeles California United States 90095
    9 Stanford University Palo Alto California United States 94304
    10 University of California, Davis Sacramento California United States 95817
    11 Yale University New Haven Connecticut United States 06510
    12 Georgetown University Washington, DC District of Columbia United States 20057
    13 Howard University Washington, DC District of Columbia United States 20060
    14 Mayo Clinic Jacksonville Florida United States 32224
    15 University of South Florida Tampa Florida United States 33617
    16 Emory University Atlanta Georgia United States 30329
    17 Northwestern University Chicago Illinois United States 60611
    18 Rush Presbyterian/St. Lukes Medical Center, Rush Alzheimer's Disease Center Chicago Illinois United States 60612
    19 Southern Illinois University Springfield Illinois United States 62794-9643
    20 Indiana University Indianapolis Indiana United States 46202
    21 Brigham and Women's Hospital Boston Massachusetts United States 02115
    22 Boston University School of Medicine Boston Massachusetts United States 02118
    23 University of Michigan Ann Arbor Michigan United States 48109
    24 University of Nevada School of Medicine, Center for Cognitive Aging Las Vegas Nevada United States 89102
    25 ClinSearch Kenilworth New Jersey United States 07033
    26 New York University Medical Center New York New York United States 10016
    27 Mt. Sinai School of Medicine New York New York United States 10029
    28 Columbia University New York New York United States 10032
    29 University of Rochester Medical Center, Alzheimer's Disease Center Rochester New York United States 14620
    30 University Memory and Aging Center, Case Western Reserve University/University Hospitals of Cleveland Cleveland Ohio United States 44120
    31 Oregon Health and Science University, Oregon Aging and Alzheimer's Disease Center Portland Oregon United States 97201
    32 University of Pennsylvania Philadelphia Pennsylvania United States 19104
    33 University of Pittsburgh Pittsburgh Pennsylvania United States 15213
    34 Memorial Hospital of Rhode Island, Alzheimer's Disease and Memory Disorder Clinic Pawtucket Rhode Island United States 02860
    35 Medical University of South Carolina North Charleston South Carolina United States 29406
    36 University of Texas, Southwestern Medical Center Dallas Texas United States 75390
    37 Baylor College of Medicine Houston Texas United States 77030
    38 University of Washington Seattle Washington United States 98108

    Sponsors and Collaborators

    • National Institute on Aging (NIA)
    • Alzheimer's Disease Cooperative Study (ADCS)


    • Principal Investigator: Paul Aisen, MD, Georgetown University, Department of Neurology

    Study Documents (Full-Text)

    None provided.

    More Information


    Responsible Party:
    , , Identifier:
    Other Study ID Numbers:
    • IA0041
    First Posted:
    Mar 10, 2003
    Last Update Posted:
    Jun 12, 2009
    Last Verified:
    Jun 1, 2009

    Study Results

    No Results Posted as of Jun 12, 2009