Resveratrol In Chronic Obstructive Pulmonary Disease (COPD) Patients (CARMENS-trial)

Study Overview
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Brief Summary
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The primary objective is to investigate the efficacy of resveratrol on mitochondrial function in patients with COPD. The secondary objective is to investigate the effect of resveratrol on body composition, inflammatory status and mechanistic markers in blood, adipose and muscle tissue as well as a comprehensive assessment of metabolicand physical performance profile known to be affected by resveratrol.

Detailed Description
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Rationale: Patients with COPD are often chaacterized by disturbed metabolic health affecting physical and cognitive function, which is reflected in altered body composition. current studies in healthy subjects suggest that resveratrol improves metabolic health by enhancing muscle mitochondrial function and adipose tissue morphology. Study design: Proof-of-concept randomized placebo-controlled double blinded clinical trial of 4 weeks. Nature and extent of the burden and risks associated with participation, benefit and group relatedness: Subjects may be confronted with certain inconveniences and risks. Subjects will be asked to wear an accelerometer two times for one week. During the entire study period subjects will visit the MUMC+ 2 times for various non-invasive measurements (questionnaires, anthropometry, and physical function test) as well as some minor invasive procedures (venous blood sampling and muscle and fat biopsies) which can cause a local haematoma afterwards. However, the patients will be informed about their metabolic and cardiovascular health, which we expect to be positively affected by the intervention. In addition, all patients will receive a lifestyle advice tailored to their health status.

Official Title
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The Effect of Resveratrol on Metabolism and Cardiovascular Risk Profile in Patients With Chronic Obstructive Pulmonary Disease (COPD)

Conditions
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Pulmonary Disease, Chronic Obstructive

Intervention / Treatment
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* Dietary Supplement: Resveratrol
* Dietary Supplement: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: COPD patients Current or ex-smoker Age >18 years Exclusion Criteria: COPD patients planned for pulmonary rehabilitation or who recently participated in a rehabilitation program in the previous 6 months Investigator's uncertainty about willingness or ability of the patient to comply with the protocol requirements Participation in any other study involving investigational exercise training, nutritional or pharmacological intervention Oral glucocorticoid use Recent exacerbation (<4 weeks) that required oral steroids and/or hospital admission Subject is pregnant, planning to be pregnant during the study period, lactating, or women who consider themselves to be of childbearing potential and who are engaged in an active sex life and are unwilling to commit to the use of an approved form of contraception throughout the study period. The method of contraception must be recorded in the source documentation; Diabetes mellitus (all types), active cardiovascular disease or a cardiovascular event (such as myocardial infarction, cerebrovascular haemorrhage/infarction) in the previous 6 months, recent major surgery, thyroid dysfunction, hepatic or renal disorders, current malignancy (except for dermal malignancies) or central or obstructive sleep apnea; Current alcohol consumption > 20 grams alcohol/day; Intake of resveratrol containing dietary supplements.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Resveratrol supplementation<br>150 mg of resveratrol for 4 weeks (split over two doses of 75 mg/day) | Dietary Supplement: Resveratrol<br>* 4 weeks of 150 mg resveratrol (2 times 75mg/day)<br>* Other names: resVida (99% pure trans-resveratrol) provided by DSM Nutritional Products, Ltd.;|
| Placebo Comparator: Placebo supplementation<br>Placebo for 4 weeks (split over two doses per day) | Dietary Supplement: Placebo<br>* 4 weeks of placebo supplementation (two doses per day)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in mitochondrial function | Assessed by measuring mitochondrial respiration (using the oxygraph) of a muscle biopsy of the quadriceps muscle (vastus lateralis) | 0 and 4 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in high sensitivity systemic inflammation (CRP) at 4 weeks | High sensitivity C-reactive protein (CRP) as a clinical marker of systemic inflammation via blood sampling. | 0 and 4 weeks | 
| Change in adipose tissue inflammation | Assessed by adipose tissue biopsy | 0 and 4 weeks | 
| Change in systematic inflammatory profile | Assessed via blood sampling | 0 and 4 weeks | 
| Change in lipid profile | Assessed via blood sampling | 0 and 4 weeks | 
| Change in insulin sensitivity | Assessed by HOMA-IR | 0 and 4 weeks | 
| Change in body composition | Assessed by: DEXA-scan Anthropometric measurements | 0 and 4 weeks | 
| Change in quadriceps function | Assessed by leg dynamometry (Biodex) | 0 and 4weeks | 
| Change in blood pressure | Measured with a hematometer | 0 and 4 weeks | 
| Change in heart rate | Measured with a hematometer | 0 and 4 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pulmonary disease, Chronic Obstructive, Cardiovascular diseases, Metabolism, Resveratrol