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

Alzheimer's Disease Clinical Trial

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00056225
• Other study ID #: IA0041
• Status: Completed
• Phase: Phase 3
• First received: March 7, 2003
• Last updated: June 10, 2009
• Start date: January 2003
• Est. completion date: June 2007

Study information

• Verified date: June 2009
• Source: National Institute on Aging (NIA)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 340
• Est. completion date: June 2007
• Est. primary completion date: June 2007
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 55 Years and older

Eligibility

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

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double-Blind, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Alzheimer Disease
• Alzheimer's Disease

Intervention

Drug:
• Folate

• Vitamin B6

• Vitamin B12

Locations

Country	Name	City	State
United States	University of Michigan	Ann Arbor	Michigan
United States	Emory University	Atlanta	Georgia
United States	University of Alabama	Birmingham	Alabama
United States	Boston University School of Medicine	Boston	Massachusetts
United States	Brigham and Women's Hospital	Boston	Massachusetts
United States	Northwestern University	Chicago	Illinois
United States	Rush Presbyterian/St. Lukes Medical Center, Rush Alzheimer's Disease Center	Chicago	Illinois
United States	University Memory and Aging Center, Case Western Reserve University/University Hospitals of Cleveland	Cleveland	Ohio
United States	University of Texas, Southwestern Medical Center	Dallas	Texas
United States	Baylor College of Medicine	Houston	Texas
United States	Indiana University	Indianapolis	Indiana
United States	University of California, Irvine, Institute for Brain Aging and Dementia	Irvine	California
United States	Mayo Clinic	Jacksonville	Florida
United States	ClinSearch	Kenilworth	New Jersey
United States	University of California, San Diego	La Jolla	California
United States	University of Nevada School of Medicine, Center for Cognitive Aging	Las Vegas	Nevada
United States	University of California, Los Angeles	Los Angeles	California
United States	University of Southern California	Los Angeles	California
United States	Yale University	New Haven	Connecticut
United States	Columbia University	New York	New York
United States	Mt. Sinai School of Medicine	New York	New York
United States	New York University Medical Center	New York	New York
United States	Medical University of South Carolina	North Charleston	South Carolina
United States	Stanford University	Palo Alto	California
United States	Memorial Hospital of Rhode Island, Alzheimer's Disease and Memory Disorder Clinic	Pawtucket	Rhode Island
United States	University of Pennsylvania	Philadelphia	Pennsylvania
United States	University of Pittsburgh	Pittsburgh	Pennsylvania
United States	Oregon Health and Science University, Oregon Aging and Alzheimer's Disease Center	Portland	Oregon
United States	University of Rochester Medical Center, Alzheimer's Disease Center	Rochester	New York
United States	University of California, Davis	Sacramento	California
United States	Mayo Clinic, Scottsdale	Scottsdale	Arizona
United States	University of Washington	Seattle	Washington
United States	Southern Illinois University	Springfield	Illinois
United States	Sun Health Research Institute	Sun City	Arizona
United States	University of South Florida	Tampa	Florida
United States	University of Arizona, Arizona Health Sciences Center	Tucson	Arizona
United States	Georgetown University	Washington, DC	District of Columbia
United States	Howard University	Washington, DC	District of Columbia

Sponsors (2)

Lead Sponsor	Collaborator
National Institute on Aging (NIA)	Alzheimer's Disease Cooperative Study (ADCS)

Country where clinical trial is conducted

United States, 

References & Publications (4)

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. — View Citation

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 — View Citation

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. — View Citation

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. — View Citation