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This is a randomized, double-blind, placebo-controlled trial evaluating the effect of resveratrol on metabolic and skeletal muscle function. Patients will be randomized and allocated to either resveratrol or placebo, for 8 weeks with a 2-week run-in period before the intervention period (to ensure they are not on any nutritional supplement that contains resveratrol).
Trial Objectives Primary outcome- Change in Isolated Skeletal Muscle Blood Flow, Oxygen Extraction and Consumption and Metabolic Rate of Recovery with Exercise by Cardiac MRI (CMR). In order to evaluate potential changes in skeletal muscle vascular function and oxygen extraction with resveratrol therapy, the investigators will use a lower limb (calf muscle) targeted exercise protocol in conjunction with magnetic resonance imaging (MRI)32. MRI will be used to measure, simultaneously, the peak rate of blood flow in the calf muscle along with the whole calf muscle extraction of oxygen, which together are used to determine oxygen consumption. This method allows the determinants of oxygen consumption (blood flow and oxygen extraction) to be evaluated, which is necessary to understand the mechanisms of therapy action.
Secondary outcomes-
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Resveratrol | Experimental | 1) Resveratrol- (Transmax) trans- resveratrol (Biotivia Longevity Bioceuticals, LLC, New York, USA) in cellulose capsules. One capsule will be taken orally 2 times per day (BID) for 8 weeks. |
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| Placebo | Placebo Comparator | 2) Placebo- 500mg (Biotivia Longevity Bioceuticals, LLC, New York, USA) in cellulose capsules. One capsule will be taken orally 2 times per day (BID) for 8 weeks. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Resveratrol | Drug | Subject participation will be approximately 10 weeks in duration. Participants will be randomized to receive one treatment: either resveratrol for 8 weeks OR placebo for 8 weeks. There will be a 2-week run-in period prior to the treatment period. The schedule for the study is: Week 0 Screening and randomization Weeks 1-2 Run-in; no treatment Weeks 3-10 Treatment Phase (resveratrol or placebo) |
| Measure | Description | Time Frame |
|---|---|---|
| Change in Isolated Skeletal Muscle Blood Flow | In order to evaluate potential changes in skeletal muscle vascular function and oxygen extraction with resveratrol therapy, the investigators will use a lower limb (calf muscle) targeted exercise protocol in conjunction with magnetic resonance imaging (MRI). MRI will be used to measure, simultaneously, the peak rate of blood flow in the calf muscle along with the whole calf muscle extraction of oxygen, which together is used to determine oxygen consumption. This method allows the determinants of oxygen consumption (blood flow and oxygen extraction) to be evaluated, which is necessary to understand the mechanisms of therapy action. | 10 weeks |
| Change in Oxygen extraction and consumption | In order to evaluate potential changes in oxygen extraction with resveratrol therapy, the investigators will use a lower limb (calf muscle) targeted exercise protocol in conjunction with magnetic resonance imaging (MRI). MRI will be used to measure, simultaneously, the peak rate of blood flow in the calf muscle along with the whole calf muscle extraction of oxygen, which together is used to determine oxygen consumption. This method allows the determinants of oxygen consumption (blood flow and oxygen extraction) to be evaluated, which is necessary to understand the mechanisms of therapy action. | 10 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| Vascular Function by CMR | Measurement of aortic distensibility will be used to assess changes in the compliance of vascular system with therapy. Compliance will be defined as the fractional change in cross-sectional area of the aorta over the cardiac cycle (measured at both ascending and descending locations) | 10 weeks |
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Inclusion Criteria:
Exclusion Criteria:
Male: Given the nature of the project and the need to have normative data for variables that may vary by sex, male patients only will be included.
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Alberta Cardiovascular and Stroke Research Centre | Edmonton | Alberta | T6G 2B7 | Canada |
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| ID | Term |
|---|---|
| D000077185 | Resveratrol |
| ID | Term |
|---|---|
| D000081225 | Stilbestrols |
| D013267 | Stilbenes |
| D001597 | Benzylidene Compounds |
| D001555 | Benzene Derivatives |
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After providing written informed consent, patients who qualify will be randomized via the web-based system coordinated by Research Electronic Data Capture (REDCap) at the University of Alberta. A patient's eligibility will be confirmed and a unique identifier will be assigned.
Blinding of the patients and study personnel is preserved by using matching placebo capsules. Clinical outcomes will be adjudicated by a Clinical Events Committee, and core laboratories will assess the CMR measures and biomarkers independently and blinded to treatment assignment.
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The randomization codes will be maintained in REDCap. The principal investigator will have authority to unblind patients if safety concerns arise.
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| Placebo | Drug | Participants will be randomized to receive one treatment: either resveratrol for 8 weeks OR placebo for 8 weeks. There will be a 2-week run-in period prior to the treatment period. |
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| D006841 |
| Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
| D059808 | Polyphenols |
| D010636 | Phenols |