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

High Dose Supplements to Reduce Homocysteine and Slow the Rate of Cognitive Decline in Alzheimer's Disease (Vitamins to Slow Alzheimer's - VITAL)

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.

Study Overview

• Status: Completed
• Conditions: Alzheimer's Disease
• Intervention / Treatment: Drug: Vitamin B12; Drug: Folate; Drug: Vitamin B6

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 Type: Interventional
• Enrollment (Actual): 340
• Phase: Phase 3

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 55 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Collaborators and Investigators

• Sponsor: National Institute on Aging (NIA)
• Collaborators: Alzheimer's Disease Cooperative Study (ADCS)
• Investigators: Principal Investigator: Paul Aisen, MD, Georgetown University, Department of Neurology

Publications and helpful links

General Publications

• 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.
• 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. doi: 10.1523/JNEUROSCI.22-05-01752.2002.
• 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.

Study record dates

Study Major Dates

• Study Start: January 1, 2003
• Primary Completion (ACTUAL): June 1, 2007
• Study Completion (ACTUAL): June 1, 2007

Study Registration Dates

• First Submitted: March 7, 2003
• First Submitted That Met QC Criteria: March 8, 2003
• First Posted (ESTIMATE): March 10, 2003

Study Record Updates

• Last Update Posted (ESTIMATE): June 12, 2009
• Last Update Submitted That Met QC Criteria: June 10, 2009
• Last Verified: June 1, 2009

More Information

Terms related to this study

• Keywords: homocysteine
• Additional Relevant MeSH Terms: Mental Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Neurodegenerative Diseases; Dementia; Tauopathies; Alzheimer Disease; Physiological Effects of Drugs; Micronutrients; Hematinics; Vitamins; Vitamin B 12; Hydroxocobalamin; Vitamin B Complex; Vitamin B 6; Pyridoxal; Pyridoxine
• Other Study ID Numbers: IA0041