Anti-Oxidant Treatment of Alzheimer's Disease

Alzheimer's Disease Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00117403
• Other study ID #: IA0067
• Status: Completed
• Phase: Phase 1
• First received: June 30, 2005
• Last updated: April 1, 2009
• Start date: January 2006
• Est. completion date: September 2007

Study information

• Verified date: April 2008
• Source: National Institute on Aging (NIA)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 75
• Est. completion date: September 2007
• Est. primary completion date: September 2007
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 60 Years to 85 Years

Eligibility

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)

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Alzheimer Disease
• Alzheimer's Disease

Intervention

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
• Coenzyme Q
400 mg, compounded as a wafer, two wafers three times per day with meals
• Placebo capsules
one placebo capsule three times per day with meals
• Placebo wafers
two placebo wafers three times per day with meals

Locations

Country	Name	City	State
United States	Case Western Reserve University	Cleveland	Ohio
United States	University of California- Irvine	Irvine	California
United States	University of California, San Diego	La Jolla	California
United States	University of Kentucky	Lexington	Kentucky
United States	University of California, Los Angeles	Los Angeles	California
United States	Wien Center, Mount Sinai Medical Center	Miami Beach	Florida
United States	Medical University of South Carolina	North Charleston	South Carolina
United States	University of Pennsylvania	Philadelphia	Pennsylvania
United States	University of Medicine and Dentistry of New Jersey	Piscataway	New Jersey
United States	Oregon Health Sciences University	Portland	Oregon
United States	University of Washington	Seattle	Washington
United States	Neurological Care of CNY	Syracuse	New York
United States	University of Arizona	Tucson	Arizona

Sponsors (2)

Lead Sponsor	Collaborator
National Institute on Aging (NIA)	Alzheimer's Disease Cooperative Study (ADCS)

Country where clinical trial is conducted

United States, 

References & Publications (3)

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

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	effect on cerebrospinal fluid (CSF) biomarkers related to oxidative damage		baseline and 4 months	No
Secondary	change in plasma and CSF concentrations of a-beta42 and a-beta40		baseline and 4 months	No