Clinical trial NCT00117403: Anti-Oxidant Treatment of Alzheimer's Disease
Official title: Evaluation of the Safety, Tolerability and Impact on Biomarkers of Anti-Oxidant Treatment of Mild to Moderate Alzheimer's Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Alzheimer's Disease
Keywords: dementia
anti-oxidant
biomarkers
alpha-tocopherol
CoQ
Lead sponsor: National Institute on Aging (NIA)
Sponsor class: NIH
Collaborators: name: Alzheimer's Disease Cooperative Study (ADCS)
First posted: 2005-07-06
Enrollment: 75
Sex: ALL
Minimum age (years): 60
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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:

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 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)

Primary outcomes:
measure: effect on cerebrospinal fluid (CSF) biomarkers related to oxidative damage
timeFrame: baseline and 4 months
Secondary outcomes:
measure: change in plasma and CSF concentrations of a-beta42 and a-beta40
timeFrame: baseline and 4 months
Other outcomes:
Locations:
city: Tucson
country: United States
facility: University of Arizona
state: Arizona
city: Irvine
country: United States
facility: University of California- Irvine
state: California
city: La Jolla
country: United States
facility: University of California, San Diego
state: California
city: Los Angeles
country: United States
facility: University of California, Los Angeles
state: California
city: Miami Beach
country: United States
facility: Wien Center, Mount Sinai Medical Center
state: Florida
city: Lexington
country: United States
facility: University of Kentucky
state: Kentucky
city: Piscataway
country: United States
facility: University of Medicine and Dentistry of New Jersey
state: New Jersey
city: Syracuse
country: United States
facility: Neurological Care of CNY
state: New York
city: Cleveland
country: United States
facility: Case Western Reserve University
state: Ohio
city: Portland
country: United States
facility: Oregon Health Sciences University
state: Oregon
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: North Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Seattle
country: United States
facility: University of Washington
state: Washington
Study officials:
affiliation: University of California, San Diego
name: Douglas Galasko, MD
role: PRINCIPAL_INVESTIGATOR
References:
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. doi: 10.1056/NEJM199704243361704.
citation: Behl C. Alzheimer's disease and oxidative stress: implications for novel therapeutic approaches. Prog Neurobiol. 1999 Feb;57(3):301-23. doi: 10.1016/s0301-0082(98)00055-0.
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. doi: 10.1001/archneur.61.1.82.
citation: 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. doi: 10.1001/archneurol.2012.85.