Resveratrol and Vascular Function in CKD

Effect of 6 Weeks Resveratrol Supplementation on Vascular Function in CKD

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.

Study Overview

• Status: Completed
• Conditions: Chronic Kidney Diseases; Endothelial Dysfunction
• Intervention / Treatment: Dietary supplement: Resveratrol; Other: Placebo

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.

• Study Type: Interventional
• Enrollment (Actual): 25
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Iowa
    • Iowa City, Iowa, United States, 52245
      • University of Iowa Hospitals and Clinics

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 45 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Resveratrol first, then placebo; Patients will receive resveratrol 400 mg PO per day in divided doses of 200 mg in the morning and 200 mg in the evening. After a minimum of 2 week washout period, subjects then took placebo for 6 weeks.	Dietary supplement: Resveratrol; Oral supplementation for 6 weeks; Other: Placebo; Oral supplementation for 6 weeks
Placebo Comparator: Placebo first, then resveratrol; Patients will receive placebo pill identical in appearance and taste to the supplement. Subjects took this placebo twice daily, once in the morning and once in the evening. After a minimum of 2 week washout period, subjects then took resveratrol for 6 weeks.	Dietary supplement: Resveratrol; Oral supplementation for 6 weeks; Other: Placebo; Oral supplementation for 6 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
% 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	First Baseline measurement to 6 weeks then Second baseline to 6 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in oxLDL	Oxidized low density lipoprotein- (LDL) cholesterol Compare the 6 weeks change from baseline with resveratrol versus placebo	6 weeks

Collaborators and Investigators

• Sponsor: Diana Jalal
• Investigators: Principal Investigator: Diana Jalal, University of Iowa

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2019
• Primary Completion (Actual): January 12, 2023
• Study Completion (Actual): January 12, 2023

Study Registration Dates

• First Submitted: July 13, 2018
• First Submitted That Met QC Criteria: July 13, 2018
• First Posted (Actual): July 24, 2018

Study Record Updates

• Last Update Posted (Estimated): November 1, 2024
• Last Update Submitted That Met QC Criteria: August 22, 2024
• Last Verified: August 1, 2024

More Information

Terms related to this study

• Keywords: Oxidative stress; Diabetes; Endothelial dysfunction; Renal Insufficiency; Kidney Diseases; Resveratrol
• Additional Relevant MeSH Terms: Urogenital Diseases; Pathologic Processes; Male Urogenital Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Chronic Disease; Disease Attributes; Renal Insufficiency; Kidney Diseases; Renal Insufficiency, Chronic; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Platelet Aggregation Inhibitors; Antioxidants; Protective Agents; Resveratrol
• Other Study ID Numbers: 201806073

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No