Tocopherols and Alpha Lipoic Acid Treatment Chronic Kidney Disease (TALAT)

Study Overview
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Brief Summary
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Oxidative stress and acute phase inflammation are now recognized to be highly prevalent in both the chronic kidney disease (CKD; pre-dialysis) and end stage renal disease (ESRD; on hemodialysis) populations, and several lines of evidence point to their contribution in the development of atherosclerosis. Biomarkers of the inflammatory state such as C-reactive protein (CRP) and interleukin-6 are robust predictors of cardiovascular events and death in these two populations. The uremic state is characterized by retention of oxidized solutes including reactive aldehyde groups and oxidized thiol groups. It has recently been demonstrated that initiation of maintenance hemodialysis does not improve biomarkers of oxidative stress or inflammation, suggesting that dialysis alone is inadequate to control the atherosclerotic uremic metabolic state. In this study we hypothesize that administration of antioxidant therapy will decrease biomarkers of acute phase inflammation and oxidative stress in patients with Stage III and IV CKD.

Official Title
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Tocopherols and Alpha Lipoic Acid Treatment Chronic Kidney Disease (TALAT)

Conditions
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Chronic Kidney Disease

Intervention / Treatment
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* Drug: Alpha, gamma, beta, and delta (mixed) tocopherols
* Drug: alpha lipoic acid
* Drug: placebo
* Drug: placebo


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Patients with Stage III-IV chronic kidney disease measured by MDRD formula. age > 18 or < 75 years. Life expectancy greater than one year. Ability to understand and provide informed consent for participation in the study Exclusion criteria: AIDS (HIV seropositivity is not an exclusion criteria) Active hepatitis C or B Active gout Other active inflammatory diseases. Active malignancy excluding basal or squamous cell carcinoma of the skin. Gastrointestinal dysfunction requiring parental nutrition. History of functional kidney transplant < 6 months prior to study entry. Anticipated live donor kidney transplant over study duration. Prisoners, patients will significant mental illness, pregnant women, and other vulnerable populations. Patients taking Vitamin E supplements > 60 IU/day, vitamin C> 500mg/day over the past 30days. Patients taking anti-inflammatory medication except aspirin < 325mg/day over the past 30 days. Patient taking any prednisone therapy. More than two hospitalizations within the last 90 days or one hospitalization within the last 30 days. On experimental drug protocols. Hypersensitivity to organic nitrates, isosorbide, or nitroglycerin. Hypersensitivity to vitamin E or alpha lipoic acid. Pregnant women

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 1<br> | Drug: Alpha, gamma, beta, and delta (mixed) tocopherols<br>* approximately 666 IU daily (1 pill) for 4 months<br>* Other names: Vitamin E;Drug: alpha lipoic acid<br>* 600 mg daily (2 pills 300 mg each) for 4 months<br>|
| Placebo Comparator: 2<br> | Drug: placebo<br>* placebo for alpha, gamma, beta, and delta (mixed) tocopherols; 1 pill daily for 4 months<br>Drug: placebo<br>* placebo for alpha lipoic acid; 2 pills daily for 4 months<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| A statistically significant decrease in F2-isoprostanes, a specific oxidative stress marker |  | 4 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| A significant change in biomarkers of acute inflammation and oxidative stress from serum |  | 4 months | 
| A significant change in brachial artery vasodilatation measured by brachial impedence plethysmography |  | 4 months |