End-stage Renal Disease
Conditions
Brief summary
Studies have shown that end stage renal disease (ESRD) patients have higher levels of blood markers which their body makes in response to increased stress and injury. An increase in these markers have been shown to be related to cardiovascular disease and death in ESRD patients. This study will examine whether antioxidant therapy (Vitamin E and alpha lipoic acid) may decrease these markers.
Detailed description
Oxidative stress and acute phase inflammation are now recognized to be highly prevalent in the hemodialysis population, and several lines of evidence point to their contribution in atherosclerosis development. Biomarkers of the inflammatory state such as C-reactive protein (CRP) and interleukin-6 are robust predictors of cardiovascular events and mortality in the dialysis population. 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 while improving the erythropoietic response in hemodialysis patients.
Interventions
approximately 666 IU daily (1 pill) for 6 months
DRUGAlpha lipoic acid
600 mg daily (2 pills 300 mg each) for 6 months
DRUGPlacebo
placebo for alpha, gamma, beta, and delta (mixed) tocopherols; 1 pill daily for 6 months
Sponsors
Fresenius Medical Care North America
Vanderbilt University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Patients with end-stage renal disease receiving thrice weekly hemodialysis 2. Age \> 18 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| F2-isoprostane (F2-iso) | month 6 | F2-iso is a sensitive laboratory assay for serum levels of F2-isoprostane, which is a biomarker of oxidative stress. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Interleukin-6 (IL-6) | month 6 | IL-6 is a sensitive laboratory assay for serum levels of interleukin-6, which is a pro-inflammatory cytokine used to evaluate the inflammatory response. |
Countries
United States
Participant flow
Recruitment details
This study was conducted at the Vanderbilt University Medical Center and at Fresenius Medical Care North America Dialysis clinics between April 2006 and September 2010.
Pre-assignment details
There is a 1-month period between enrollment and assignment to a treatment group. Although 385 subjects were enrolled, only 356 were randomized (29 subjects withdrew consent prior to randomization). Also, 31 subjects were administratively withdrawn (due to widespread protocol non-compliance at one site) leaving 325 subjects assigned to a group.
Participants by arm
| Arm | Count |
|---|---|
| ALA and Vitamin E 600 mg (2 pills 300 mg each) of alpha lipoic acid (ALA) and 666 IU (1 pill) of mixed (alpha, gamma, beta and delta) tocopherols (Vitamin E) taken orally on a daily basis for 6 months | 160 |
| Placebo placebo for ALA (2 pills) and for Vitamin E (1 pill) taken orally on a daily basis for 6 months | 165 |
| Total | 325 |
Baseline characteristics
| Characteristic | Placebo | Total | ALA and Vitamin E |
|---|---|---|---|
| Age Continuous | 58 years STANDARD_DEVIATION 13 | 58 years STANDARD_DEVIATION 12 | 58 years STANDARD_DEVIATION 12 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 2 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 90 Participants | 188 Participants | 98 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 6 Participants | 7 Participants | 1 Participants |
| Race (NIH/OMB) White | 69 Participants | 128 Participants | 59 Participants |
| Sex: Female, Male Female | 69 Participants | 143 Participants | 74 Participants |
| Sex: Female, Male Male | 96 Participants | 182 Participants | 86 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 91 / 160 | 85 / 165 |
| serious Total, serious adverse events | 44 / 160 | 52 / 165 |
Outcome results
Primary
F2-isoprostane (F2-iso)
F2-iso is a sensitive laboratory assay for serum levels of F2-isoprostane, which is a biomarker of oxidative stress.
Time frame: month 6
Population: The number of participants for analysis was based on those subjects who completed the 6-month study. Note that 8 subjects were excluded due to samples being lost. The analysis was per protocol.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| ALA and Vitamin E | F2-isoprostane (F2-iso) | 0.077 ng/ml | Standard Deviation 0.062 |
| Placebo | F2-isoprostane (F2-iso) | 0.073 ng/ml | Standard Deviation 0.055 |
p-value: >0.05ANCOVA
Secondary
Interleukin-6 (IL-6)
IL-6 is a sensitive laboratory assay for serum levels of interleukin-6, which is a pro-inflammatory cytokine used to evaluate the inflammatory response.
Time frame: month 6
Population: The number of participants for analysis was based on those subjects who completed the 6-month study. Note that 8 subjects were excluded due to samples being lost. The analysis was per protocol.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| ALA and Vitamin E | Interleukin-6 (IL-6) | 19 pg/ml | Standard Deviation 15 |
| Placebo | Interleukin-6 (IL-6) | 20 pg/ml | Standard Deviation 27 |
p-value: >0.05ANCOVA