Provision of Antioxidant Therapy in Hemodialysis (PATH) Study

Study Overview
=================
Brief Summary
-----------------
Studies have shown that end stage renal disease (ESRD) patients have higher levels of blood markers which their body makes in response to increased stress and injury. An increase in these markers have been shown to be related to cardiovascular disease and death in ESRD patients. This study will examine whether antioxidant therapy (Vitamin E and alpha lipoic acid) may decrease these markers.

Detailed Description
-----------------
Oxidative stress and acute phase inflammation are now recognized to be highly prevalent in the hemodialysis population, and several lines of evidence point to their contribution in atherosclerosis development. Biomarkers of the inflammatory state such as C-reactive protein (CRP) and interleukin-6 are robust predictors of cardiovascular events and mortality in the dialysis population. 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 while improving the erythropoietic response in hemodialysis patients.

Official Title
-----------------
Provision of Antioxidant Therapy in Hemodialysis (PATH) Study

Conditions
-----------------
End-stage Renal Disease

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


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patients with end-stage renal disease receiving thrice weekly hemodialysis Age > 18 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 malignancy excluding basal cell carcinoma of the skin Gastrointestinal dysfunction requiring parenteral nutrition History of functional kidney transplant < 6 months prior to study entry Anticipated live donor kidney transplant over study duration History of poor adherence to hemodialysis or medical regimen Prisoners, patients with significant mental illness, pregnant women, and other vulnerable populations Patients taking vitamin E supplements > 60 IU/day, vitamin C > 500 mg/day over the past 30 days Patients taking anti-inflammatory medication except aspirin < 325 mg/day over the past 30 days Patients using a temporary catheter for dialysis access More than two hospitalizations within the last 90 days or one hospitalization within the last 30 days

Ages Eligible for Study
-----------------
Minimum Age: 18 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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: ALA and Vitamin E<br>600 mg (2 pills 300 mg each) of alpha lipoic acid (ALA) and 666 IU (1 pill) of alpha, gamma, beta and delta (mixed) tocopherols (Vitamin E) taken orally on a daily basis for 6 months | Drug: Alpha, gamma, beta, and delta (mixed) tocopherols<br>* approximately 666 IU daily (1 pill) for 6 months<br>* Other names: Vitamin E;Drug: Alpha lipoic acid<br>* 600 mg daily (2 pills 300 mg each) for 6 months<br>|
| Placebo Comparator: Placebo<br>placebo for ALA (2 pills) and for Vitamin E (1 pill) taken orally on a daily basis for 6 months | Drug: Placebo<br>* placebo for alpha, gamma, beta, and delta (mixed) tocopherols; 1 pill daily for 6 months<br>Drug: Placebo<br>* placebo for alpha lipoic acid; 2 pills daily for 6 months<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| F2-isoprostane (F2-iso) | F2-iso is a sensitive laboratory assay for serum levels of F2-isoprostane, which is a biomarker of oxidative stress. | month 6 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Interleukin-6 (IL-6) | IL-6 is a sensitive laboratory assay for serum levels of interleukin-6, which is a pro-inflammatory cytokine used to evaluate the inflammatory response. | month 6 |