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

Sponsor:	National Institute on Aging (NIA)
Collaborator:	Alzheimer's Disease Cooperative Study (ADCS)
Information provided by:	National Institute on Aging (NIA)
ClinicalTrials.gov Identifier:	NCT00056225

Purpose

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	Intervention	Phase
Alzheimer's Disease	Drug: Folate Drug: Vitamin B6 Drug: Vitamin B12	Phase III

Study Type:	Interventional
Study Design:	Treatment, Randomized, Double-Blind, Placebo Control, Parallel Assignment, Safety/Efficacy Study
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)

Resource links provided by NLM:

Genetics Home Reference related topics: Alzheimer disease

MedlinePlus related topics: Alzheimer's Disease Dietary Supplements

Drug Information available for: Pyridoxine hydrochloride Pyridoxine Vitamin B 12 Hydroxocobalamin Homocysteine Vitamin B 6

U.S. FDA Resources

Further study details as provided by National Institute on Aging (NIA):

Enrollment:	340
Study Start Date:	January 2003
Study Completion Date:	June 2007
Primary Completion Date:	June 2007 (Final data collection date for primary outcome measure)

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.

Eligibility

Ages Eligible for Study:	55 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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

Please refer to this study by its ClinicalTrials.gov identifier: NCT00056225

Hide Study Locations

Locations

United States, Alabama
University of Alabama
Birmingham, Alabama, United States, 35294
United States, Arizona
University of Arizona, Arizona Health Sciences Center
Tucson, Arizona, United States, 85724
Mayo Clinic, Scottsdale
Scottsdale, Arizona, United States, 85259
Sun Health Research Institute
Sun City, Arizona, United States, 85351
United States, California
University of California, San Diego
La Jolla, California, United States, 92093-0624
University of California, Davis
Sacramento, California, United States, 95817
University of California, Irvine, Institute for Brain Aging and Dementia
Irvine, California, United States, 92697
University of California, Los Angeles
Los Angeles, California, United States, 90095
Stanford University
Palo Alto, California, United States, 94304
University of Southern California
Los Angeles, California, United States, 90033
United States, Connecticut
Yale University
New Haven, Connecticut, United States, 06510
United States, District of Columbia
Georgetown University
Washington, DC, District of Columbia, United States, 20057
Howard University
Washington, DC, District of Columbia, United States, 20060
United States, Florida
University of South Florida
Tampa, Florida, United States, 33617
Mayo Clinic
Jacksonville, Florida, United States, 32224
United States, Georgia
Emory University
Atlanta, Georgia, United States, 30329
United States, Illinois
Northwestern University
Chicago, Illinois, United States, 60611
Rush Presbyterian/St. Lukes Medical Center, Rush Alzheimer's Disease Center
Chicago, Illinois, United States, 60612
Southern Illinois University
Springfield, Illinois, United States, 62794-9643
United States, Indiana
Indiana University
Indianapolis, Indiana, United States, 46202
United States, Massachusetts
Boston University School of Medicine
Boston, Massachusetts, United States, 02118
Brigham and Women's Hospital
Boston, Massachusetts, United States, 02115
United States, Michigan
University of Michigan
Ann Arbor, Michigan, United States, 48109
United States, Nevada
University of Nevada School of Medicine, Center for Cognitive Aging
Las Vegas, Nevada, United States, 89102
United States, New Jersey
ClinSearch
Kenilworth, New Jersey, United States, 07033
United States, New York
Columbia University
New York, New York, United States, 10032
Mt. Sinai School of Medicine
New York, New York, United States, 10029
New York University Medical Center
New York, New York, United States, 10016
University of Rochester Medical Center, Alzheimer's Disease Center
Rochester, New York, United States, 14620
United States, Ohio
University Memory and Aging Center, Case Western Reserve University/University Hospitals of Cleveland
Cleveland, Ohio, United States, 44120
United States, Oregon
Oregon Health and Science University, Oregon Aging and Alzheimer's Disease Center
Portland, Oregon, United States, 97201
United States, Pennsylvania
University of Pennsylvania
Philadelphia, Pennsylvania, United States, 19104
University of Pittsburgh
Pittsburgh, Pennsylvania, United States, 15213
United States, Rhode Island
Memorial Hospital of Rhode Island, Alzheimer's Disease and Memory Disorder Clinic
Pawtucket, Rhode Island, United States, 02860
United States, South Carolina
Medical University of South Carolina
North Charleston, South Carolina, United States, 29406
United States, Texas
Baylor College of Medicine
Houston, Texas, United States, 77030
University of Texas, Southwestern Medical Center
Dallas, Texas, United States, 75390
United States, Washington
University of Washington
Seattle, Washington, United States, 98108

Sponsors and Collaborators

National Institute on Aging (NIA)

Alzheimer's Disease Cooperative Study (ADCS)

Investigators

Principal Investigator:

Paul Aisen, MD

Georgetown University, Department of Neurology

More Information

Publications:

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.

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.

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.

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.

Study ID Numbers:	IA0041
Study First Received:	March 7, 2003
Last Updated:	June 10, 2009
ClinicalTrials.gov Identifier:	NCT00056225 History of Changes
Health Authority:	United States: Federal Government

Keywords provided by National Institute on Aging (NIA):

homocysteine

Additional relevant MeSH terms:

Vitamin B Complex
Growth Substances
Physiological Effects of Drugs
Alzheimer Disease
Nervous System Diseases
Central Nervous System Diseases
Vitamin B 12
Brain Diseases
Neurodegenerative Diseases

Pharmacologic Actions
Vitamin B 6
Delirium, Dementia, Amnestic, Cognitive Disorders
Mental Disorders
Vitamins
Micronutrients
Dementia
Tauopathies

ClinicalTrials.gov processed this record on November 27, 2009