Chronic Kidney Diseases, Endothelial Dysfunction
Conditions
Keywords
Resveratrol, Kidney Diseases, Renal Insufficiency, Diabetes, Oxidative stress, Endothelial dysfunction
Brief summary
The proposed research is clinical study evaluating the therapeutic benefits of resveratrol on vascular function in patients with chronic kidney disease (CKD). The study aims to establish that resveratrol will improve endothelial function and functional performance by reducing oxidative stress and in conjunction with lowering markers of inflammation and oxidative stress.
Detailed description
Patients with chronic kidney disease (CKD) have an exceptionally high risk for cardiovascular disease (CVD), and are 10 times more likely to die from CVD prior to requiring dialysis or kidney transplantation. Inflammation, oxidative stress and vascular dysfunction (impaired endothelial function and increased large elastic artery stiffness), are highly prevalent in CKD and contribute to the high incidence of CVD in this patient population. In addition, patients with CKD suffer from high rates of cognitive decline for which we lack effective therapies. Thus, therapeutic interventions targeting inflammation, oxidative stress, vascular dysfunction in CKD are a priority. Wine intake, which is known to be rich in various polyphenolic compounds, might have a variety of health benefits. Among these polyphenols, the stilbene derivative resveratrol (RSV), a naturally occurring polyphenol found in grapes and red wine, has recently come to light, as it has been shown to exert potent anti-diabetic, anti-oxidative and anti-inflammatory actions. Importantly, recent studies have demonstrated that resveratrol is well-tolerated (37) and may confer similar benefits in individuals at high risk of CVD, such as improved endothelial function in individuals with metabolic syndrome (i.e. diabetes) The primary goal of this application is to determine whether 6 wks resveratrol (RSV) supplementation improves vascular function by reducing oxidative stress in a randomized, double-blind, cross-over study of 25 patients with diabetic kidney disease. The investigators hypothesize that: 1) 6 wks RSV will improve vascular function as measured via BA-FMD vs. placebo and 2) that the improvement in vascular function will be related, at least partially, to a reduction in oxidative stress.
Interventions
Oral supplementation for 6 weeks
Oral supplementation for 6 weeks
Sponsors
Study design
Intervention model description
Subjects will be randomized to either receive the following intervention: placebo or resveratrol for six weeks and then after a two week washout will be assigned the alternate study drug.
Eligibility
Inclusion criteria
* CKD stage III (estimated GFR: 30-60 mL/MIN/1.73m2) * Able to give informed consent * Angiotensin converting enzyme inhibitor or angiotensin II receptor bloocker for \> 3 month prior to the study * Type II diabetes mellitus
Exclusion criteria
* Consuming \> 2 glasses/day red wine and/or taking resveratrol or vitamin C supplement in the past 12 months * Life expectancy \<1 year * BMI \>40 kg/m2 1 * Pregnant, breastfeeding, or unwilling to use adequate birth control * Uncontrolled hypertension; blood pressure \> 140/90 * Uncontrolled type II DM; AIC \> 8.5 * Currently taking anticoagulants including: coumadin, dalteparin, enoxaparin, haparin, and plavix. * Severe liver disease * Severe systolic heart failure * Hospitalization within the last 3 months * Active infection or antibiotic therapy * Immunosuppressive therapy within the last year * Currently partaking in another research study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| % Change of Brachial Artery Flow-mediated Dilation | First Baseline measurement to 6 weeks then Second baseline to 6 weeks | Brachial artery flow-mediated dilation, dilation of the brachial artery in response to shear stress. Resveratrol first, then placebo: Baseline to 6 weeks on Resveratrol Minimum 2 week washout Baseline to 6 week on placebo Placebo first, then resveratrol: Baseline to 6 weeks on placebo Minimum washout 2 weeks Baseline to 6 weeks on resveratrol |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in oxLDL | 6 weeks | Oxidized low density lipoprotein- (LDL) cholesterol Compare the 6 weeks change from baseline with resveratrol versus placebo |
Countries
United States
Participant flow
Recruitment details
Consented 28 and randomized 25
Pre-assignment details
Randomized cross over design, each subject served as their own control. Randomized either to placebo first or resveratrol first. There was 2 week wash-out period.
Participants by arm
| Arm | Count |
|---|---|
| Resveratrol First Randomized cross over design, subjects received either resveratrol or placebo first, 2 weeks washout separated the 2 treatments | 13 |
| Placebo First Randomized cross over design, subjects received either resveratrol or placebo first, 2 weeks washout separated the 2 treatments | 12 |
| Total | 25 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Unable to analyze vascular data | 1 | 1 |
| Overall Study | Withdrawal by Subject | 1 | 1 |
Baseline characteristics
| Characteristic | Resveratrol First | Placebo First | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 11 Participants | 8 Participants | 19 Participants |
| Age, Categorical Between 18 and 65 years | 2 Participants | 2 Participants | 4 Participants |
| Age, Continuous | 68 years | 69 years | 68 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 13 Participants | 10 Participants | 23 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 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 | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 13 Participants | 10 Participants | 23 Participants |
| Region of Enrollment United States | 13 participants | 10 participants | 23 participants |
| Sex: Female, Male Female | 2 Participants | 1 Participants | 3 Participants |
| Sex: Female, Male Male | 11 Participants | 9 Participants | 20 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 25 | 0 / 25 |
| other Total, other adverse events | 3 / 25 | 0 / 25 |
| serious Total, serious adverse events | 1 / 25 | 0 / 25 |
Outcome results
% Change of Brachial Artery Flow-mediated Dilation
Brachial artery flow-mediated dilation, dilation of the brachial artery in response to shear stress. Resveratrol first, then placebo: Baseline to 6 weeks on Resveratrol Minimum 2 week washout Baseline to 6 week on placebo Placebo first, then resveratrol: Baseline to 6 weeks on placebo Minimum washout 2 weeks Baseline to 6 weeks on resveratrol
Time frame: First Baseline measurement to 6 weeks then Second baseline to 6 weeks
Population: Randomized cross over design
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Resveratrol | % Change of Brachial Artery Flow-mediated Dilation | 1.3 %change |
| Placebo | % Change of Brachial Artery Flow-mediated Dilation | 0.91 %change |
Change in oxLDL
Oxidized low density lipoprotein- (LDL) cholesterol Compare the 6 weeks change from baseline with resveratrol versus placebo
Time frame: 6 weeks
Population: oxLDL was measured and change from baseline was compared for both groups.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Resveratrol | Change in oxLDL | 1.66 U/L |
| Placebo | Change in oxLDL | 1.38 U/L |