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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 1 | Active Comparator |
| |
| 2 | Placebo Comparator |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Alpha, gamma, beta, and delta (mixed) tocopherols | Drug | approximately 666 IU daily (1 pill) for 4 months |
|
| Measure | Description | Time Frame |
|---|---|---|
| A statistically significant decrease in F2-isoprostanes, a specific oxidative stress marker | 4 months |
| Measure | Description | 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 |
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Inclusion criteria:
Exclusion criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Jonathan Himmelfarb, MD | MaineHealth | Principal Investigator |
| Alp Ikizler, MD | Vanderbilt University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Maine Medical Center | Portland | Maine | 04102 | United States | ||
| Vanderbilt University Medical Center |
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| ID | Term |
|---|---|
| D051436 | Renal Insufficiency, Chronic |
| ID | Term |
|---|---|
| D051437 | Renal Insufficiency |
| D007674 | Kidney Diseases |
| D014570 | Urologic Diseases |
| D052776 | Female Urogenital Diseases |
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| ID | Term |
|---|---|
| D005720 | Gamma Rays |
| D050986 | YY1 Transcription Factor |
| D024505 | Tocopherols |
| D014810 | Vitamin E |
| D008063 | Thioctic Acid |
| ID | Term |
|---|---|
| D060733 | Electromagnetic Radiation |
| D055590 | Electromagnetic Phenomena |
| D060328 | Magnetic Phenomena |
| D055585 | Physical Phenomena |
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| alpha lipoic acid | Drug | 600 mg daily (2 pills 300 mg each) for 4 months |
|
| placebo | Drug | placebo for alpha, gamma, beta, and delta (mixed) tocopherols; 1 pill daily for 4 months |
|
| placebo | Drug | placebo for alpha lipoic acid; 2 pills daily for 4 months |
|
| Nashville |
| Tennessee |
| 37232 |
| United States |
| D005261 |
| Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
| D052801 | Male Urogenital Diseases |
| D002908 | Chronic Disease |
| D020969 | Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D011827 | Radiation |
| D011839 | Radiation, Ionizing |
| D050981 | Erythroid-Specific DNA-Binding Factors |
| D004268 | DNA-Binding Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D014157 | Transcription Factors |
| D001578 | Benzopyrans |
| D011714 | Pyrans |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D002264 | Carboxylic Acids |
| D009930 | Organic Chemicals |
| D013876 | Thiophenes |
| D013457 | Sulfur Compounds |
| D003067 | Coenzymes |
| D045762 | Enzymes and Coenzymes |
| D005227 | Fatty Acids |
| D008055 | Lipids |