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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Resveratrol first, then placebo | Experimental | 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. |
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| Placebo first, then resveratrol | Placebo Comparator | 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Resveratrol | Dietary Supplement | Oral supplementation for 6 weeks |
|
| 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 |
| 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 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Diana Jalal | University of Iowa | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Iowa Hospitals and Clinics | Iowa City | Iowa | 52245 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 37843843 | Derived | Gimblet CJ, Kruse NT, Geasland K, Michelson J, Sun M, Mandukhail SR, Wendt LH, Eyck PT, Pierce GL, Jalal DI. Effect of Resveratrol on Endothelial Function in Patients with CKD and Diabetes: A Randomized Controlled Trial. Clin J Am Soc Nephrol. 2024 Feb 1;19(2):161-168. doi: 10.2215/CJN.0000000000000337. Epub 2023 Oct 16. |
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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.
Consented 28 and randomized 25
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| ID | Title | Description |
|---|---|---|
| FG000 | Resveratrol First | Subjects received resveratrol 400 mg PO per day for 6 weeks then placebo after 2 week wash out period |
| FG001 | Placebo First | Subjects received placebo identical to the study drug for 6 weeks then resveratrol at 400 mg a day after a 2 week wash out |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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Each subject functioned as their own control in this randomized cross over study
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| ID | Title | Description |
|---|---|---|
| BG000 | Resveratrol First | Randomized cross over design, subjects received either resveratrol or placebo first, 2 weeks washout separated the 2 treatments |
| BG001 | Placebo First | Randomized cross over design, subjects received either resveratrol or placebo first, 2 weeks washout separated the 2 treatments |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | 2 subjects in total in both arms did not have vascular images that could be analyzed. |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | % 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 | Randomized cross over design | Posted | Mean | 95% Confidence Interval | %change | First Baseline measurement to 6 weeks then Second baseline to 6 weeks |
|
6 weeks of resveratrol supplementation
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Resveratrol | 6 weeks randomized cross over study, randomized to resveratrol first or placebo first, there was 2 week wash out period |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Dyspnea | Respiratory, thoracic and mediastinal disorders | Non-systematic Assessment | Subject reported dyspnea and admitted to hospital for supplemental oxygen. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Diarrhea | Gastrointestinal disorders | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Diana Jalal | University of I | 319-338-0581 | diana-jalal@uiowa.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Feb 23, 2024 | Feb 23, 2024 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D051436 | Renal Insufficiency, Chronic |
| D007674 | Kidney Diseases |
| D051437 | Renal Insufficiency |
| D003920 | Diabetes Mellitus |
| ID | Term |
|---|---|
| D014570 | Urologic Diseases |
| D052776 | Female Urogenital Diseases |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
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| ID | Term |
|---|---|
| D000077185 | Resveratrol |
| ID | Term |
|---|---|
| D000081225 | Stilbestrols |
| D013267 | Stilbenes |
| D001597 | Benzylidene Compounds |
| D001555 | Benzene Derivatives |
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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.
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| Placebo | Other | Oral supplementation for 6 weeks |
|
| BG002 | Total | Total of all reporting groups |
| Count of Participants |
| Participants |
|
| Age, Continuous | Mean | Full Range | years |
|
| Sex: Female, Male | 2 subjects did not have vascular images that could be analyzed | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | 2 subjects did not have vascular images that could be analyzed | Count of Participants | Participants |
|
| Race (NIH/OMB) | 2 subjects did not have vascular images that could be analyzed | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
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Randomized cross over design
|
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| Secondary | Change in oxLDL | Oxidized low density lipoprotein- (LDL) cholesterol Compare the 6 weeks change from baseline with resveratrol versus placebo | oxLDL was measured and change from baseline was compared for both groups. | Posted | Mean | 95% Confidence Interval | U/L | 6 weeks |
|
|
|
| 0 |
| 25 |
| 1 |
| 25 |
| 3 |
| 25 |
| EG001 | Placebo | 6 weeks randomized cross over study, randomized to resveratrol first or placebo first, there was 2 week wash out period | 0 | 25 | 0 | 25 | 0 | 25 |
|
| Dizziness | General disorders | Systematic Assessment |
|
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| D052801 | Male Urogenital Diseases |
| D002908 | Chronic Disease |
| D020969 | Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D044882 | Glucose Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
| D004700 | Endocrine System Diseases |
| D006841 |
| Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
| D059808 | Polyphenols |
| D010636 | Phenols |
| Unknown or Not Reported |
|
| Native Hawaiian or Other Pacific Islander |
|
| Black or African American |
|
| White |
|
| More than one race |
|
| Unknown or Not Reported |
|