Clinical trial NCT00308971: Tocopherols and Alpha Lipoic Acid Treatment Chronic Kidney Disease (TALAT)
Official title: Tocopherols and Alpha Lipoic Acid Treatment Chronic Kidney Disease (TALAT)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Chronic Kidney Disease
Lead sponsor: Vanderbilt University
Sponsor class: OTHER
First posted: 2006-03-30
Enrollment: 62
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: A statistically significant decrease in F2-isoprostanes, a specific oxidative stress marker
timeFrame: 4 months
Secondary outcomes:
measure: A significant change in biomarkers of acute inflammation and oxidative stress from serum
timeFrame: 4 months
measure: A significant change in brachial artery vasodilatation measured by brachial impedence plethysmography
timeFrame: 4 months
Other outcomes:
Locations:
city: Portland
country: United States
facility: Maine Medical Center
state: Maine
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
Study officials:
affiliation: MaineHealth
name: Jonathan Himmelfarb, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Vanderbilt University
name: Alp Ikizler, MD
role: PRINCIPAL_INVESTIGATOR
References: