Anti-Oxidant Treatment of Alzheimer's Disease - Full Text View

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:

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:

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.

Eligibility


Ages Eligible for Study:	60 Years to 85 Years (Adult, Senior)
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

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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:

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.

Behl C. Alzheimer's disease and oxidative stress: implications for novel therapeutic approaches. Prog Neurobiol. 1999 Feb;57(3):301-23. Review.

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.

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

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.


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 Vitamins Vitamin E Tocopherols Tocotrienols Alpha-Tocopherol Vitamin B Complex Dementia Brain Diseases Central Nervous System Diseases Nervous System Diseases Tauopathies	Neurodegenerative Diseases Neurocognitive Disorders Mental Disorders Ascorbic Acid Thioctic Acid Antioxidants Ubiquinone Micronutrients Growth Substances Physiological Effects of Drugs Molecular Mechanisms of Pharmacological Action Protective Agents

ClinicalTrials.gov processed this record on September 26, 2016