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

Overview

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 Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Parallel Assignment
    • Primary Purpose: Treatment
    • Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
  • Study Primary Completion Date: July 2007

Interventions

  • Drug: Alpha, gamma, beta, and delta (mixed) tocopherols
    • approximately 666 IU daily (1 pill) for 4 months
  • Drug: alpha lipoic acid
    • 600 mg daily (2 pills 300 mg each) for 4 months
  • 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

Arms, Groups and Cohorts

  • Active Comparator: 1
  • Placebo Comparator: 2

Clinical Trial Outcome Measures

Primary Measures

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

Secondary Measures

  • A significant change in biomarkers of acute inflammation and oxidative stress from serum
    • Time Frame: 4 months
  • A significant change in brachial artery vasodilatation measured by brachial impedence plethysmography
    • Time Frame: 4 months

Participating in This Clinical Trial

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

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: 75 Years

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • Vanderbilt University
  • Provider of Information About this Clinical Study
    • Alp Ikizler, MD, Vanderbilt University Medical Center
  • Overall Official(s)
    • Jonathan Himmelfarb, MD, Principal Investigator, Maine Medical Center
    • Alp Ikizler, MD, Principal Investigator, Vanderbilt University

Clinical trials entries are delivered from the US National Institutes of Health and are not reviewed separately by this site. Please see the identifier information above for retrieving further details from the government database.

At TrialBulletin.com, we keep tabs on over 200,000 clinical trials in the US and abroad, using medical data supplied directly by the US National Institutes of Health. Please see the About and Contact page for details.