Anti-Oxidant Treatment of Alzheimer's Disease

NCT ID: NCT00117403

Last Updated: 2009-04-03

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 75 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2006-01-31
• Study Completion Date: 2007-09-30

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).

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:

1. 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;

2. 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;

3. 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.

Conditions

Alzheimer's Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

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

Group Type: EXPERIMENTAL

Vitamin E, Vitamin C, and Alpha-lipoic Acid

Intervention Type: DRUG

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

Placebo wafers

Intervention Type: DRUG

two placebo wafers three times per day with meals

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

Group Type: EXPERIMENTAL

Coenzyme Q

Intervention Type: DRUG

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

Placebo capsules

Intervention Type: DRUG

one placebo capsule three times per day with meals

3

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

Group Type: PLACEBO_COMPARATOR

Placebo capsules

Intervention Type: DRUG

one placebo capsule three times per day with meals

Placebo wafers

Intervention Type: DRUG

two placebo wafers three times per day with meals

Interventions

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

Intervention Type: DRUG

Coenzyme Q

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

Intervention Type: DRUG

Placebo capsules

one placebo capsule three times per day with meals

Intervention Type: DRUG

Placebo wafers

two placebo wafers three times per day with meals

Intervention Type: DRUG

Eligibility Criteria

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)

• Minimum Eligible Age: 60 Years
• Maximum Eligible Age: 85 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Alzheimer's Disease Cooperative Study (ADCS)

OTHER

Sponsor Role: collaborator

National Institute on Aging (NIA)

NIH

Sponsor Role: lead

Responsible Party

Alzheimer's Disease Cooperative Study

Principal Investigators

Douglas Galasko, MD

Role: PRINCIPAL_INVESTIGATOR

University of California, San Diego

Locations

University of Arizona

Tucson, Arizona, United States

University of California- Irvine

Irvine, California, United States

University of California, San Diego

La Jolla, California, United States

University of California, Los Angeles

Los Angeles, California, United States

Wien Center, Mount Sinai Medical Center

Miami Beach, Florida, United States

University of Kentucky

Lexington, Kentucky, United States

University of Medicine and Dentistry of New Jersey

Piscataway, New Jersey, United States

Neurological Care of CNY

Syracuse, New York, United States

Case Western Reserve University

Cleveland, Ohio, United States

Oregon Health Sciences University

Portland, Oregon, United States

University of Pennsylvania

Philadelphia, Pennsylvania, United States

Medical University of South Carolina

North Charleston, South Carolina, United States

University of Washington

Seattle, Washington, United States

Countries

United States

References

Sano M, Ernesto C, Thomas RG, Klauber MR, Schafer K, Grundman M, Woodbury P, Growdon J, Cotman CW, Pfeiffer E, Schneider LS, Thal LJ. A controlled trial of selegiline, alpha-tocopherol, or both as treatment for Alzheimer's disease. The Alzheimer's Disease Cooperative Study. N Engl J Med. 1997 Apr 24;336(17):1216-22. doi: 10.1056/NEJM199704243361704.

Reference Type: BACKGROUND

PMID: 9110909 (View on PubMed)

Behl C. Alzheimer's disease and oxidative stress: implications for novel therapeutic approaches. Prog Neurobiol. 1999 Feb;57(3):301-23. doi: 10.1016/s0301-0082(98)00055-0.

Reference Type: BACKGROUND

PMID: 10096843 (View on PubMed)

Zandi PP, Anthony JC, Khachaturian AS, Stone SV, Gustafson D, Tschanz JT, Norton MC, Welsh-Bohmer KA, Breitner JC; Cache County Study Group. Reduced risk of Alzheimer disease in users of antioxidant vitamin supplements: the Cache County Study. Arch Neurol. 2004 Jan;61(1):82-8. doi: 10.1001/archneur.61.1.82.

Reference Type: BACKGROUND

PMID: 14732624 (View on PubMed)

Galasko DR, Peskind E, Clark CM, Quinn JF, Ringman JM, Jicha GA, Cotman C, Cottrell B, Montine TJ, Thomas RG, Aisen P; Alzheimer's Disease Cooperative Study. Antioxidants for Alzheimer disease: a randomized clinical trial with cerebrospinal fluid biomarker measures. Arch Neurol. 2012 Jul;69(7):836-41. doi: 10.1001/archneurol.2012.85.

Reference Type: DERIVED

PMID: 22431837 (View on PubMed)

Other Identifiers

IA0067

Identifier Type: -

Identifier Source: org_study_id