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

Sponsor

Vanderbilt University (Other)

Overall Status

Completed

CT.gov ID

NCT00308971

Collaborator

(none)

Enrollment

Locations

Arms

Duration (Months)

Patients Per Site

1.9

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Chronic Kidney Disease	Drug: Alpha, gamma, beta, and delta (mixed) tocopherols Drug: alpha lipoic acid Drug: placebo Drug: placebo	Phase 2

Study Design

Study Type:

Interventional

Actual Enrollment :

62 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Mar 1, 2006

Actual Primary Completion Date :

Jul 1, 2007

Actual Study Completion Date :

Jul 1, 2007

Arms and Interventions

Arm	Intervention/Treatment
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
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

Arm

Intervention/Treatment

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

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

Outcome Measures

Primary Outcome Measures

A statistically significant decrease in F2-isoprostanes, a specific oxidative stress marker [4 months]

Secondary Outcome Measures

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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion criteria:

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