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

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.

Study Overview

• Status: Completed
• Conditions: Chronic Kidney Disease
• Intervention / Treatment: Drug: Alpha, gamma, beta, and delta (mixed) tocopherols; Drug: alpha lipoic acid; Drug: placebo; Drug: placebo

• Study Type: Interventional
• Enrollment (Actual): 62
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Maine
    • Portland, Maine, United States, 04102
      • Maine Medical Center
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt University Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion criteria:

1. Patients with Stage III-IV chronic kidney disease measured by MDRD formula.
2. age > 18 or < 75 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 hepatitis C or B
3. Active gout
4. Other active inflammatory diseases.
5. Active malignancy excluding basal or squamous cell carcinoma of the skin.
6. Gastrointestinal dysfunction requiring parental nutrition.
7. History of functional kidney transplant < 6 months prior to study entry.
8. Anticipated live donor kidney transplant over study duration.
9. Prisoners, patients will significant mental illness, pregnant women, and other vulnerable populations.
10. Patients taking Vitamin E supplements > 60 IU/day, vitamin C> 500mg/day over the past 30days.
11. Patients taking anti-inflammatory medication except aspirin < 325mg/day over the past 30 days.
12. Patient taking any prednisone therapy.
13. More than two hospitalizations within the last 90 days or one hospitalization within the last 30 days.
14. On experimental drug protocols.
15. Hypersensitivity to organic nitrates, isosorbide, or nitroglycerin.
16. Hypersensitivity to vitamin E or alpha lipoic acid.
17. Pregnant women

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
Placebo Comparator: 2	Drug: placebo; placebo for alpha, gamma, beta, and delta (mixed) tocopherols; 1 pill daily for 4 months; Drug: placebo; placebo for alpha lipoic acid; 2 pills daily for 4 months
Active Comparator: 1	Drug: Alpha, gamma, beta, and delta (mixed) tocopherols; approximately 666 IU daily (1 pill) for 4 months; Other Names: Vitamin E; Drug: alpha lipoic acid; 600 mg daily (2 pills 300 mg each) for 4 months

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Vanderbilt University
• Investigators: Principal Investigator: Jonathan Himmelfarb, MD, MaineHealth

Study record dates

Study Major Dates

• Study Start: March 1, 2006
• Primary Completion (Actual): July 1, 2007
• Study Completion (Actual): July 1, 2007

Study Registration Dates

• First Submitted: March 28, 2006
• First Submitted That Met QC Criteria: March 28, 2006
• First Posted (Estimate): March 30, 2006

Study Record Updates

• Last Update Posted (Estimate): July 9, 2009
• Last Update Submitted That Met QC Criteria: July 8, 2009
• Last Verified: July 1, 2009

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urologic Diseases; Renal Insufficiency; Kidney Diseases; Renal Insufficiency, 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: 051000

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No