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

• ClinicalTrials.gov Identifier: NCT00056225
• Recruitment Status: Completed
• First Posted: March 10, 2003
• Last Update Posted: June 12, 2009
• Sponsor: National Institute on Aging (NIA)
• Collaborator: Alzheimer's Disease Cooperative Study (ADCS)
• Information provided by: National Institute on Aging (NIA)

Tracking Information

• First Submitted Date: March 7, 2003
• First Posted Date: March 10, 2003
• Last Update Posted Date: June 12, 2009
• Study Start Date: January 2003
• Actual Primary Completion Date: June 2007 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures: Not Provided
• Original Primary Outcome Measures: Not Provided
• Current Secondary Outcome Measures: Not Provided
• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: VITAL - VITamins to Slow ALzheimer's Disease (Homocysteine 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)
• 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.

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
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double; Primary Purpose: Treatment
• Condition: Alzheimer's Disease

Intervention

• Drug: Folate
• Drug: Vitamin B6
• Drug: Vitamin B12

• Study Arms: Not Provided

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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: October 20, 2008): 340
• Original Enrollment (submitted: June 23, 2005): 400
• Actual Study Completion Date: June 2007
• Actual Primary Completion Date: June 2007 (Final data collection date for primary outcome measure)

Eligibility 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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 55 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT00056225
• Other Study ID Numbers: IA0041
• Has Data Monitoring Committee: Not Provided
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Not Provided
• Original Responsible Party: Same as current
• Current Study Sponsor: National Institute on Aging (NIA)
• Original Study Sponsor: Same as current
• Collaborators: Alzheimer's Disease Cooperative Study (ADCS)

Investigators

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

• PRS Account: National Institute on Aging (NIA)
• Verification Date: June 2009