Anti-Oxidant Treatment of Alzheimer's Disease

Study Overview
=================
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: 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.

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

Conditions
-----------------
Alzheimer's Disease

Intervention / Treatment
-----------------
* Drug: Vitamin E, Vitamin C, and Alpha-lipoic Acid
* Drug: Coenzyme Q
* Drug: Placebo capsules
* Drug: Placebo wafers


Participation Criteria
=================
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)

Ages Eligible for Study
-----------------
Minimum Age: 60 Years
Maximum Age: 85 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>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<br>* 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<br>Drug: Placebo wafers<br>* two placebo wafers three times per day with meals<br>|
| Experimental: 2<br>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<br>* 400 mg, compounded as a wafer, two wafers three times per day with meals<br>Drug: Placebo capsules<br>* one placebo capsule three times per day with meals<br>|
| Placebo Comparator: 3<br>two placebo wafers three times per day with meals, plus one placebo capsule three times per day with meals | Drug: Placebo capsules<br>* one placebo capsule three times per day with meals<br>Drug: Placebo wafers<br>* two placebo wafers three times per day with meals<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| effect on cerebrospinal fluid (CSF) biomarkers related to oxidative damage |  | baseline and 4 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| change in plasma and CSF concentrations of a-beta42 and a-beta40 |  | baseline and 4 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
CoQ, dementia, anti-oxidant, biomarkers, alpha-tocopherol