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

Sponsor

National Institute on Aging (NIA) (NIH)

Overall Status

Completed

CT.gov ID

NCT00056225

Collaborator

Alzheimer's Disease Cooperative Study (ADCS) (Other)

340

Enrollment

Locations

Duration (Months)

8.9

Patients Per Site

0.2

Patients Per Site Per Month

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
Alzheimer's Disease	Drug: Folate Drug: Vitamin B6 Drug: Vitamin B12	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:

Interventional

Actual Enrollment :

340 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Double

Primary Purpose:

Treatment

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

Criteria

Ages Eligible for Study:

55 Years and Older

Sexes Eligible for Study:

All

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

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