Provision of Antioxidant Therapy in Hemodialysis (PATH) Study

Vanderbilt University

Status and phase: Completed; Phase 2

Conditions: End-stage Renal Disease

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

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT00237718

050377

Details and patient eligibility

About

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.

Full 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.

Enrollment: 385 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Patients with end-stage renal disease receiving thrice weekly hemodialysis
2. Age > 18 years
3. Life expectancy greater than one year
4. Ability to understand and provide informed consent for participation in the study

Exclusion criteria

1. AIDS (HIV seropositivity is not an exclusion criteria)
2. Active malignancy excluding basal cell carcinoma of the skin
3. Gastrointestinal dysfunction requiring parenteral nutrition
4. History of functional kidney transplant < 6 months prior to study entry
5. Anticipated live donor kidney transplant over study duration
6. History of poor adherence to hemodialysis or medical regimen
7. Prisoners, patients with significant mental illness, pregnant women, and other vulnerable populations
8. Patients taking vitamin E supplements > 60 IU/day, vitamin C > 500 mg/day over the past 30 days
9. Patients taking anti-inflammatory medication except aspirin < 325 mg/day over the past 30 days
10. Patients using a temporary catheter for dialysis access
11. More than two hospitalizations within the last 90 days or one hospitalization within the last 30 days

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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385 participants in 2 patient groups, including a placebo group

ALA and Vitamin E

Active Comparator group

Description:

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

Treatment:

Drug: Alpha, gamma, beta, and delta (mixed) tocopherols

Drug: Alpha lipoic acid

Placebo

Placebo Comparator group

Description:

placebo for ALA (2 pills) and for Vitamin E (1 pill) taken orally on a daily basis for 6 months

Treatment:

Drug: Placebo

Drug: Placebo