Anti-Oxidant Treatment of Alzheimer's Disease

Sponsor

National Institute on Aging (NIA) (NIH)

Overall Status

Completed

CT.gov ID

NCT00117403

Collaborator

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

Enrollment

Locations

Arms

Duration (Months)

5.8

Patients Per Site

0.3

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to examine the safety and effectiveness of two anti-oxidant treatment regimens in patients with mild to moderate Alzheimer's disease. The anti-oxidant treatments include vitamin E + C + alpha-lipoic acid, and Coenzyme Q (CoQ).

Condition or Disease	Intervention/Treatment	Phase
Alzheimer's Disease	Drug: Vitamin E, Vitamin C, and Alpha-lipoic Acid Drug: Coenzyme Q Drug: Placebo capsules Drug: Placebo wafers	Phase 1

Detailed Description

Oxidative damage has been shown to be a factor in Alzheimer's disease (AD), and some studies have suggested that supplemental anti-oxidants can decrease the risk of AD or slow its progression. There are many candidate antioxidants, including combinations, which could be neuroprotective in established AD or could have efficacy in the prevention of AD. However, testing each of the possibilities in standard clinical trials is prohibitively expensive. This study will examine antioxidant supplements or vitamins which target specific cellular compartments, and look for evidence of biologically relevant effects in AD by measurement of biomarkers in CSF.

Two general cellular compartments where antioxidant supplements may act are the cytosol and mitochondria. The study will examine a combination of antioxidants that act primarily at cytosolic sites (vitamin E + C + α-lipoic acid) and a single mitochondrial antioxidant, coenzyme Q10.

This multicenter trial will recruit 75 participants who will be randomized into three groups:

25 participants will be given a combination of vitamin E 800 IU, vitamin C 200 mg, and alpha-lipoic acid 600 mg formulated into three capsules, one capsule given three times per day with meals, plus two placebo wafers three times per day with meals;
25 participants will be given CoQ 400 mg, compounded as a wafer, two wafers three times per day with meals, plus one placebo capsule three times per day with meals;
25 participants will be given both the placebo wafers, two wafers three times per day with meals, plus one placebo capsule three times per day with meals.

The treatment period will last four months. The effects of the two anti-oxidant treatments will be evaluated by measuring biomarkers in blood and cerebrospinal fluid (CSF) at the beginning and end of the 4-month period.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

75 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Double (Participant, Investigator)

Primary Purpose:

Treatment

Official Title:

Evaluation of the Safety, Tolerability and Impact on Biomarkers of Anti-Oxidant Treatment of Mild to Moderate Alzheimer's Disease

Study Start Date :

Jan 1, 2006

Actual Primary Completion Date :

Sep 1, 2007

Actual Study Completion Date :

Sep 1, 2007

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 1 vitamin E 800 IU, vitamin C 200 mg, and alpha-lipoic acid 600 mg formulated into three capsules, one capsule given three times per day with meals, plus two placebo wafers three times per day with meals	Drug: Vitamin E, Vitamin C, and Alpha-lipoic Acid vitamin E 800 IU, vitamin C 200 mg, and alpha-lipoic acid 600 mg formulated into three capsules, one capsule given three times per day with meals Drug: Placebo wafers two placebo wafers three times per day with meals
Experimental: 2 CoQ 400 mg, compounded as a wafer, two wafers three times per day with meals, plus one placebo capsule three times per day with meals	Drug: Coenzyme Q 400 mg, compounded as a wafer, two wafers three times per day with meals Drug: Placebo capsules one placebo capsule three times per day with meals
Placebo Comparator: 3 two placebo wafers three times per day with meals, plus one placebo capsule three times per day with meals	Drug: Placebo capsules one placebo capsule three times per day with meals Drug: Placebo wafers two placebo wafers three times per day with meals

Arm

Intervention/Treatment

Experimental: 1

vitamin E 800 IU, vitamin C 200 mg, and alpha-lipoic acid 600 mg formulated into three capsules, one capsule given three times per day with meals, plus two placebo wafers three times per day with meals

Drug: Vitamin E, Vitamin C, and Alpha-lipoic Acid

vitamin E 800 IU, vitamin C 200 mg, and alpha-lipoic acid 600 mg formulated into three capsules, one capsule given three times per day with meals

Drug: Placebo wafers

two placebo wafers three times per day with meals

Experimental: 2

CoQ 400 mg, compounded as a wafer, two wafers three times per day with meals, plus one placebo capsule three times per day with meals

Drug: Coenzyme Q

400 mg, compounded as a wafer, two wafers three times per day with meals

Drug: Placebo capsules

one placebo capsule three times per day with meals

Placebo Comparator: 3

two placebo wafers three times per day with meals, plus one placebo capsule three times per day with meals

Drug: Placebo capsules

one placebo capsule three times per day with meals

Drug: Placebo wafers

two placebo wafers three times per day with meals

Outcome Measures

Primary Outcome Measures

effect on cerebrospinal fluid (CSF) biomarkers related to oxidative damage [baseline and 4 months]

Secondary Outcome Measures

change in plasma and CSF concentrations of a-beta42 and a-beta40 [baseline and 4 months]

Eligibility Criteria

Criteria

Ages Eligible for Study:

60 Years to 85 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Men or women aged 60-85, inclusive
Diagnosis of probable Alzheimer's disease
English-speaking; Spanish-speaking if individual site allows
Study partner or caregiver to assure compliance
Mini-Mental State Examination score at screening visit greater than 14
Female participants either surgically sterile or postmenopausal for over 1 year
Stable medical condition for 3 months prior to screening, with no significant abnormal liver, kidney, or blood studies
Stable medications for 4 weeks prior to screening
Able to take oral medications
Modified Hachinski Ischemic Index less than or equal to 4
CT or MRI since onset of memory impairment demonstrating the absence of a clinically significant focal lesion
Physically acceptable for this study as confirmed by medical history, physical exam, neurological exam, and clinical tests

Exclusion Criteria:

Significant neurologic disease such as Parkinson's disease, stroke, brain tumor, multiple sclerosis, or seizure disorder
Major depression in the past 12 months, major mental illness such as schizophrenia, or recent (in past 12 months) alcohol or substance abuse
History of invasive cancer within the past two years (excluding non-melanoma skin cancer)
Contra-indications to lumbar puncture
Use of any investigational agents within 30 days prior to screening
Major surgery within 8 weeks prior to the Baseline Visit
Uncontrolled cardiac conditions or severe unstable medical illnesses
Antiretroviral therapy for human immunodeficiency virus (HIV)
Conditions that will contribute to oxidative stress: current cigarette or cigar smokers (within past month), diabetics on insulin or poorly controlled on oral hypoglycemics
Residence in skilled nursing facility
Blindness, deafness, language difficulties or any other disability which may prevent the participant from participating or cooperating in the protocol

Note: Exceptions to these criteria may be considered on a case-by-case basis, at the discretion of the Project Director.

Excluded Medications:

Experimental drugs
Coumadin
Insulin
Immunosuppressive agents: prednisone and other corticosteroids (taken orally or by injection), methotrexate, cyclophosphamide, cyclosporin, tacrolimus, etc.
HIV protease inhibitors
Neuroleptics and lithium
Anti-cancer agents (exception: stable doses of hormonal therapy, e.g. Lupron, estrogen, are permitted)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Arizona	Tucson	Arizona	United States	85724
2	University of California- Irvine	Irvine	California	United States	92697
3	University of California, San Diego	La Jolla	California	United States	92037
4	University of California, Los Angeles	Los Angeles	California	United States	90095
5	Wien Center, Mount Sinai Medical Center	Miami Beach	Florida	United States	33140
6	University of Kentucky	Lexington	Kentucky	United States	40536
7	University of Medicine and Dentistry of New Jersey	Piscataway	New Jersey	United States	08855
8	Neurological Care of CNY	Syracuse	New York	United States	13210
9	Case Western Reserve University	Cleveland	Ohio	United States	44120
10	Oregon Health Sciences University	Portland	Oregon	United States	97239
11	University of Pennsylvania	Philadelphia	Pennsylvania	United States	19104
12	Medical University of South Carolina	North Charleston	South Carolina	United States	29406
13	University of Washington	Seattle	Washington	United States	98108