Provision of Antioxidant Therapy in Hemodialysis (PATH) Study

Phase 2

Completed

Interventions: Drug: Alpha, gamma, beta, and delta (mixed) tocopherols
Drug: Placebo
Drug: Alpha lipoic acid

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.

Recruitment & Eligibility

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

Arm && Interventions

Group	Intervention	Description
ALA and Vitamin E	Alpha, gamma, beta, and delta (mixed) tocopherols	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
Placebo	Placebo	placebo for ALA (2 pills) and for Vitamin E (1 pill) taken orally on a daily basis for 6 months
ALA and Vitamin E	Alpha lipoic acid	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

Primary Outcome Measures

Name	Time	Method
F2-isoprostane (F2-iso)	month 6	F2-iso is a sensitive laboratory assay for serum levels of F2-isoprostane, which is a biomarker of oxidative stress.

Secondary Outcome Measures

Name	Time	Method
Interleukin-6 (IL-6)	month 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.