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

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

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.

Study Overview

• Status: Completed
• Conditions: Pulmonary Disease, Chronic Obstructive
• Intervention / Treatment: Dietary supplement: Resveratrol; Dietary supplement: Placebo

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 23
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Netherlands
  • Limburg
    • Maastricht, Limburg, Netherlands
      • Maastricht University Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Medical history	Medication use	0 and 4 weeks
Physical activity	Assessed by: Accelerometry; Short Questionnaire to Assess Health (SQUASH)	0 and 4 weeks
Severity of dyspnea and COPD	Assessed by: Medical Research Council scale (MRC-scale); COPD assessment test (CAT); Clinical COPD Questionnaire (CCQ)	0 and 4 weeks
Sleep pattern	Assess by Pittburgh Sleep Quality Index (PSQI)	0 and 4 weeks
Food intake	Assessed by food anamnesis questionnaire	0 and 4 weeks
Resveratrol and dihydroresveratrol concentrations	Assessed by blood sampling	0 and 4 weeks
Electrocardiogram	Measured with a ECG	0 and 4 weeks
Safety parameters	Assessed in blood: Creatinine; Urea; Sodium; Potassium; Gamma-GT; ALAT; ASAT; Alkaline Phosphatase	0 and 4 weeks
Baseline lung function	Assessed by spirometry	0 weeks

Collaborators and Investigators

• Sponsor: Maastricht University Medical Center
• Collaborators: DSM Nutritional Products, Inc.; The Netherlands Asthma Foundation
• Investigators: Principal Investigator: Annemie Schols, Prof., Maastricht University Medical Center

Publications and helpful links

General Publications

• Timmers S, Konings E, Bilet L, Houtkooper RH, van de Weijer T, Goossens GH, Hoeks J, van der Krieken S, Ryu D, Kersten S, Moonen-Kornips E, Hesselink MKC, Kunz I, Schrauwen-Hinderling VB, Blaak E, Auwerx J, Schrauwen P. Calorie restriction-like effects of 30 days of resveratrol supplementation on energy metabolism and metabolic profile in obese humans. Cell Metab. 2011 Nov 2;14(5):612-22. doi: 10.1016/j.cmet.2011.10.002.
• van den Borst B, Gosker HR, Schols AM. Central fat and peripheral muscle: partners in crime in chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2013 Jan 1;187(1):8-13. doi: 10.1164/rccm.201208-1441OE. No abstract available.
• Beijers RJ, Gosker HR, Sanders KJ, de Theije C, Kelders M, Clarke G, Cryan JF, van den Borst B, Schols AM. Resveratrol and metabolic health in COPD: A proof-of-concept randomized controlled trial. Clin Nutr. 2020 Oct;39(10):2989-2997. doi: 10.1016/j.clnu.2020.01.002. Epub 2020 Jan 13.

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2015
• Primary Completion (Actual): November 1, 2017
• Study Completion (Actual): November 1, 2017

Study Registration Dates

• First Submitted: September 16, 2014
• First Submitted That Met QC Criteria: September 18, 2014
• First Posted (Estimate): September 22, 2014

Study Record Updates

• Last Update Posted (Actual): May 17, 2019
• Last Update Submitted That Met QC Criteria: May 16, 2019
• Last Verified: September 1, 2016

More Information

Terms related to this study

• Keywords: Cardiovascular diseases; Resveratrol; Metabolism; Pulmonary disease, Chronic Obstructive
• Additional Relevant MeSH Terms: Pathologic Processes; Respiratory Tract Diseases; Disease Attributes; Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive; Chronic Disease; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Platelet Aggregation Inhibitors; Protective Agents; Antioxidants; Resveratrol
• Other Study ID Numbers: 143031; 3.4.12.023 (Other Grant/Funding Number: The Netherlands Lung Foundation)