Provision of Antioxidant Therapy in Hemodialysis (PATH) Study

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.

Study Overview

• Status: Completed
• Conditions: End-stage Renal Disease
• Intervention / Treatment: Drug: Alpha, gamma, beta, and delta (mixed) tocopherols; Drug: Alpha lipoic acid; Drug: Placebo; Drug: Placebo

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.

• Study Type: Interventional
• Enrollment (Actual): 385
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Tennessee
    • Nashville, Tennessee, United States, 37215
      • Fresenius Medical Care North America

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

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

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

Collaborators and Investigators

• Sponsor: Vanderbilt University
• Collaborators: Fresenius Medical Care North America
• Investigators: Principal Investigator: Jonathan Himmelfarb, MD, MaineHealth; Principal Investigator: Alp Ikizler, MD, Vanderbilt University Medical Center

Study record dates

Study Major Dates

• Study Start: April 1, 2006
• Primary Completion (Actual): September 1, 2010
• Study Completion (Actual): September 1, 2010

Study Registration Dates

• First Submitted: October 10, 2005
• First Submitted That Met QC Criteria: October 10, 2005
• First Posted (Estimate): October 12, 2005

Study Record Updates

• Last Update Posted (Estimate): January 11, 2012
• Last Update Submitted That Met QC Criteria: January 9, 2012
• Last Verified: January 1, 2012

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Kidney Diseases; Urologic Diseases; Renal Insufficiency; Renal Insufficiency, Chronic; Kidney Failure, Chronic; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Protective Agents; Micronutrients; Vitamins; Antioxidants; Vitamin B Complex; Vitamin E; Tocopherols; alpha-Tocopherol; Tocotrienols; Thioctic Acid
• Other Study ID Numbers: 050377