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	Intervention	Phase
Alzheimer''''s Disease	Drug: Vitamin E  Drug: Vitamin C  Drug: Alpha-lipoic acid  Drug: Coenzyme Q	Phase I

Further Study Details: 

Primary Outcomes: effect on cerebrospinal fluid (CSF) biomarkers related to oxidative damage
Secondary Outcomes: change in plasma and CSF concentrations of a-beta42 and a-beta40
Expected Total Enrollment:  75

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 compounded as a single capsule, once per day, 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 per day;

3. 25 participants will be given both the placebo wafers, two wafers three times per day with meals, plus one placebo capsule per day.

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.

Ages Eligible for Study:  60 Years   -   85 Years,  Genders Eligible for Study:  Both

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)

Please refer to this study by ClinicalTrials.gov identifier  NCT00117403

Alabama
      University of Alabama, Birmingham,  Alabama,  35294,  United States
Arizona
      University of Arizona, Tucson,  Arizona,  85724,  United States
California
      Stanford University, Palo Alto,  California,  94304,  United States
      University of California, Los Angeles, Los Angeles,  California,  90095,  United States
      University of California, San Diego, La Jolla,  California,  92037,  United States
Florida
      Baumel-Eisner Neuromedical Institute, Ft. Lauderdale,  Florida,  33321,  United States
      Baumel-Eisner Neuromedical Institute, Miami Beach,  Florida,  33154,  United States
New York
      Neurological Care of CNY, Syracuse,  New York,  13210,  United States
      New York University Medical Center, New York,  New York,  10016,  United States
Ohio
      Case Western Reserve University, Cleveland,  Ohio,  44120,  United States
Oregon
      Oregon Health Sciences University, Portland,  Oregon,  97239,  United States
Pennsylvania
      University of Pennsylvania, Philadelphia,  Pennsylvania,  19104,  United States
South Carolina
      Medical University of South Carolina, North Charleston,  South Carolina,  29406,  United States
Washington
      University of Washington, Seattle,  Washington,  98108,  United States

Study chairs or principal investigators

Douglas Galasko, MD,  Principal Investigator,  University of California, San Diego   

Study ID Numbers:  IA0067
Record last reviewed:  June 2005
Last Updated:  July 25, 2005
Record first received:  July 5, 2005
ClinicalTrials.gov Identifier:  NCT00117403
Health Authority: United States: Food and Drug Administration
ClinicalTrials.gov processed this record on 2005-07-26