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Anti-Oxidant Treatment of Alzheimer's Disease

This study has been completed.
Sponsor:
Collaborator:
Alzheimer's Disease Cooperative Study (ADCS)
Information provided by:
National Institute on Aging (NIA)
ClinicalTrials.gov Identifier:
NCT00117403
First received: June 30, 2005
Last updated: April 1, 2009
Last verified: April 2008
History of Changes
  Purpose

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, Vitamin C, and Alpha-lipoic Acid
Drug: Coenzyme Q
Drug: Placebo capsules
Drug: Placebo wafers
 Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, 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

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by National Institute on Aging (NIA):

Primary Outcome Measures:
  • effect on cerebrospinal fluid (CSF) biomarkers related to oxidative damage [ Time Frame: baseline and 4 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • change in plasma and CSF concentrations of a-beta42 and a-beta40 [ Time Frame: baseline and 4 months ] [ Designated as safety issue: No ]

Estimated Enrollment: 75
Study Start Date: January 2006
Study Completion Date: September 2007
Primary Completion Date: September 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.

  Eligibility

Ages Eligible for Study:   60 Years to 85 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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)
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00117403

Locations
United States, Arizona
University of Arizona
Tucson, Arizona, United States, 85724
United States, California
University of California- Irvine
Irvine, California, United States, 92697
University of California, San Diego
La Jolla, California, United States, 92037
University of California, Los Angeles
Los Angeles, California, United States, 90095
United States, Florida
Wien Center, Mount Sinai Medical Center
Miami Beach, Florida, United States, 33140
United States, Kentucky
University of Kentucky
Lexington, Kentucky, United States, 40536
United States, New Jersey
University of Medicine and Dentistry of New Jersey
Piscataway, New Jersey, United States, 08855
United States, New York
Neurological Care of CNY
Syracuse, New York, United States, 13210
United States, Ohio
Case Western Reserve University
Cleveland, Ohio, United States, 44120
United States, Oregon
Oregon Health Sciences University
Portland, Oregon, United States, 97239
United States, Pennsylvania
University of Pennsylvania
Philadelphia, Pennsylvania, United States, 19104
United States, South Carolina
Medical University of South Carolina
North Charleston, South Carolina, United States, 29406
United States, Washington
University of Washington
Seattle, Washington, United States, 98108
Sponsors and Collaborators
National Institute on Aging (NIA)
Alzheimer's Disease Cooperative Study (ADCS)
Investigators
Principal Investigator: Douglas Galasko, MD University of California, San Diego
  More Information

Publications:

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Responsible Party: Paul Aisen, MD, Alzheimer's Disease Cooperative Study
ClinicalTrials.gov Identifier: NCT00117403     History of Changes
Other Study ID Numbers: IA0067
Study First Received: June 30, 2005
Last Updated: April 1, 2009
Health Authority: United States: Food and Drug Administration

Keywords provided by National Institute on Aging (NIA):
dementia
anti-oxidant
biomarkers
alpha-tocopherol
CoQ

Additional relevant MeSH terms:
Alzheimer Disease
Dementia
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Tauopathies
Neurodegenerative Diseases
Delirium, Dementia, Amnestic, Cognitive Disorders
Mental Disorders
Antioxidants
Ascorbic Acid
Thioctic Acid
Vitamin E
 Alpha-Tocopherol
Tocopherols
Tocotrienols
Vitamins
Ubiquinone
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Protective Agents
Physiological Effects of Drugs
Micronutrients
Growth Substances
Vitamin B Complex

ClinicalTrials.gov processed this record on May 21, 2013