<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT02245932</url>
  </required_header>
  <id_info>
    <org_study_id>143031</org_study_id>
    <secondary_id>3.4.12.023</secondary_id>
    <nct_id>NCT02245932</nct_id>
  </id_info>
  <brief_title>Resveratrol In Chronic Obstructive Pulmonary Disease (COPD) Patients (CARMENS-trial)</brief_title>
  <acronym>CARMENS</acronym>
  <official_title>The Effect of Resveratrol on Metabolism and Cardiovascular Risk Profile in Patients With Chronic Obstructive Pulmonary Disease (COPD)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Maastricht University Medical Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>The Netherlands Asthma Foundation</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>DSM Nutritional Products, Inc.</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Maastricht University Medical Center</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The primary objective is to investigate the efficacy of resveratrol on mitochondrial function&#xD;
      in patients with COPD. The secondary objective is to investigate the effect of resveratrol on&#xD;
      body composition, inflammatory status and mechanistic markers in blood, adipose and muscle&#xD;
      tissue as well as a comprehensive assessment of metabolicand physical performance profile&#xD;
      known to be affected by resveratrol.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Rationale: Patients with COPD are often chaacterized by disturbed metabolic health affecting&#xD;
      physical and cognitive function, which is reflected in altered body composition. current&#xD;
      studies in healthy subjects suggest that resveratrol improves metabolic health by enhancing&#xD;
      muscle mitochondrial function and adipose tissue morphology.&#xD;
&#xD;
      Study design: Proof-of-concept randomized placebo-controlled double blinded clinical trial of&#xD;
      4 weeks.&#xD;
&#xD;
      Nature and extent of the burden and risks associated with participation, benefit and group&#xD;
      relatedness: Subjects may be confronted with certain inconveniences and risks. Subjects will&#xD;
      be asked to wear an accelerometer two times for one week. During the entire study period&#xD;
      subjects will visit the MUMC+ 2 times for various non-invasive measurements (questionnaires,&#xD;
      anthropometry, and physical function test) as well as some minor invasive procedures (venous&#xD;
      blood sampling and muscle and fat biopsies) which can cause a local haematoma afterwards.&#xD;
      However, the patients will be informed about their metabolic and cardiovascular health, which&#xD;
      we expect to be positively affected by the intervention. In addition, all patients will&#xD;
      receive a lifestyle advice tailored to their health status.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">January 2015</start_date>
  <completion_date type="Actual">November 2017</completion_date>
  <primary_completion_date type="Actual">November 2017</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Prevention</primary_purpose>
    <masking>Triple (Participant, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change in mitochondrial function</measure>
    <time_frame>0 and 4 weeks</time_frame>
    <description>Assessed by measuring mitochondrial respiration (using the oxygraph) of a muscle biopsy of the quadriceps muscle (vastus lateralis)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change from baseline in high sensitivity systemic inflammation (CRP) at 4 weeks</measure>
    <time_frame>0 and 4 weeks</time_frame>
    <description>High sensitivity C-reactive protein (CRP) as a clinical marker of systemic inflammation via blood sampling.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in adipose tissue inflammation</measure>
    <time_frame>0 and 4 weeks</time_frame>
    <description>Assessed by adipose tissue biopsy</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in systematic inflammatory profile</measure>
    <time_frame>0 and 4 weeks</time_frame>
    <description>Assessed via blood sampling</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in lipid profile</measure>
    <time_frame>0 and 4 weeks</time_frame>
    <description>Assessed via blood sampling</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in insulin sensitivity</measure>
    <time_frame>0 and 4 weeks</time_frame>
    <description>Assessed by HOMA-IR</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in body composition</measure>
    <time_frame>0 and 4 weeks</time_frame>
    <description>Assessed by:&#xD;
DEXA-scan&#xD;
Anthropometric measurements</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in quadriceps function</measure>
    <time_frame>0 and 4weeks</time_frame>
    <description>Assessed by leg dynamometry (Biodex)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in blood pressure</measure>
    <time_frame>0 and 4 weeks</time_frame>
    <description>Measured with a hematometer</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in heart rate</measure>
    <time_frame>0 and 4 weeks</time_frame>
    <description>Measured with a hematometer</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Medical history</measure>
    <time_frame>0 and 4 weeks</time_frame>
    <description>Medication use</description>
  </other_outcome>
  <other_outcome>
    <measure>Physical activity</measure>
    <time_frame>0 and 4 weeks</time_frame>
    <description>Assessed by:&#xD;
Accelerometry&#xD;
Short Questionnaire to Assess Health (SQUASH)</description>
  </other_outcome>
  <other_outcome>
    <measure>Severity of dyspnea and COPD</measure>
    <time_frame>0 and 4 weeks</time_frame>
    <description>Assessed by:&#xD;
Medical Research Council scale (MRC-scale)&#xD;
COPD assessment test (CAT)&#xD;
Clinical COPD Questionnaire (CCQ)</description>
  </other_outcome>
  <other_outcome>
    <measure>Sleep pattern</measure>
    <time_frame>0 and 4 weeks</time_frame>
    <description>Assess by Pittburgh Sleep Quality Index (PSQI)</description>
  </other_outcome>
  <other_outcome>
    <measure>Food intake</measure>
    <time_frame>0 and 4 weeks</time_frame>
    <description>Assessed by food anamnesis questionnaire</description>
  </other_outcome>
  <other_outcome>
    <measure>Resveratrol and dihydroresveratrol concentrations</measure>
    <time_frame>0 and 4 weeks</time_frame>
    <description>Assessed by blood sampling</description>
  </other_outcome>
  <other_outcome>
    <measure>Electrocardiogram</measure>
    <time_frame>0 and 4 weeks</time_frame>
    <description>Measured with a ECG</description>
  </other_outcome>
  <other_outcome>
    <measure>Safety parameters</measure>
    <time_frame>0 and 4 weeks</time_frame>
    <description>Assessed in blood:&#xD;
Creatinine&#xD;
Urea&#xD;
Sodium&#xD;
Potassium&#xD;
Gamma-GT&#xD;
ALAT&#xD;
ASAT&#xD;
Alkaline Phosphatase</description>
  </other_outcome>
  <other_outcome>
    <measure>Baseline lung function</measure>
    <time_frame>0 weeks</time_frame>
    <description>Assessed by spirometry</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">23</enrollment>
  <condition>Pulmonary Disease, Chronic Obstructive</condition>
  <arm_group>
    <arm_group_label>Resveratrol supplementation</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>150 mg of resveratrol for 4 weeks (split over two doses of 75 mg/day)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo supplementation</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Placebo for 4 weeks (split over two doses per day)</description>
  </arm_group>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Resveratrol</intervention_name>
    <description>4 weeks of 150 mg resveratrol (2 times 75mg/day)</description>
    <arm_group_label>Resveratrol supplementation</arm_group_label>
    <other_name>resVida (99% pure trans-resveratrol) provided by DSM Nutritional Products, Ltd.</other_name>
  </intervention>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>4 weeks of placebo supplementation (two doses per day)</description>
    <arm_group_label>Placebo supplementation</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  COPD patients&#xD;
&#xD;
          -  Current or ex-smoker&#xD;
&#xD;
          -  Age &gt;18 years&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  COPD patients planned for pulmonary rehabilitation or who recently participated in a&#xD;
             rehabilitation program in the previous 6 months&#xD;
&#xD;
          -  Investigator's uncertainty about willingness or ability of the patient to comply with&#xD;
             the protocol requirements&#xD;
&#xD;
          -  Participation in any other study involving investigational exercise training,&#xD;
             nutritional or pharmacological intervention&#xD;
&#xD;
          -  Oral glucocorticoid use&#xD;
&#xD;
          -  Recent exacerbation (&lt;4 weeks) that required oral steroids and/or hospital admission&#xD;
&#xD;
          -  Subject is pregnant, planning to be pregnant during the study period, lactating, or&#xD;
             women who consider themselves to be of childbearing potential and who are engaged in&#xD;
             an active sex life and are unwilling to commit to the use of an approved form of&#xD;
             contraception throughout the study period. The method of contraception must be&#xD;
             recorded in the source documentation;&#xD;
&#xD;
          -  Diabetes mellitus (all types), active cardiovascular disease or a cardiovascular event&#xD;
             (such as myocardial infarction, cerebrovascular haemorrhage/infarction) in the&#xD;
             previous 6 months, recent major surgery, thyroid dysfunction, hepatic or renal&#xD;
             disorders, current malignancy (except for dermal malignancies) or central or&#xD;
             obstructive sleep apnea;&#xD;
&#xD;
          -  Current alcohol consumption &gt; 20 grams alcohol/day;&#xD;
&#xD;
          -  Intake of resveratrol containing dietary supplements.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Annemie Schols, Prof.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Maastricht University Medical Center</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Maastricht University Medical Center</name>
      <address>
        <city>Maastricht</city>
        <state>Limburg</state>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Netherlands</country>
  </location_countries>
  <reference>
    <citation>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.</citation>
    <PMID>22055504</PMID>
  </reference>
  <reference>
    <citation>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.</citation>
    <PMID>23281350</PMID>
  </reference>
  <verification_date>September 2016</verification_date>
  <study_first_submitted>September 16, 2014</study_first_submitted>
  <study_first_submitted_qc>September 18, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 22, 2014</study_first_posted>
  <last_update_submitted>May 16, 2019</last_update_submitted>
  <last_update_submitted_qc>May 16, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">May 17, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Pulmonary disease, Chronic Obstructive</keyword>
  <keyword>Cardiovascular diseases</keyword>
  <keyword>Metabolism</keyword>
  <keyword>Resveratrol</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Lung Diseases</mesh_term>
    <mesh_term>Lung Diseases, Obstructive</mesh_term>
    <mesh_term>Pulmonary Disease, Chronic Obstructive</mesh_term>
    <mesh_term>Chronic Disease</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Resveratrol</mesh_term>
  </intervention_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT02245932
org study id: 143031
secondary id: 3.4.12.023
nct id: NCT02245932
lead sponsor: 
collaborator: 
collaborator: 
has dmc: Yes
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.
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.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Prevention
masking: Triple (Participant, Investigator, Outcomes Assessor)
measure: Change in mitochondrial function
time frame: 0 and 4 weeks
description: Assessed by measuring mitochondrial respiration (using the oxygraph) of a muscle biopsy of the quadriceps muscle (vastus lateralis)
measure: Change from baseline in high sensitivity systemic inflammation (CRP) at 4 weeks
time frame: 0 and 4 weeks
description: High sensitivity C-reactive protein (CRP) as a clinical marker of systemic inflammation via blood sampling.
measure: Change in adipose tissue inflammation
time frame: 0 and 4 weeks
description: Assessed by adipose tissue biopsy
measure: Change in systematic inflammatory profile
time frame: 0 and 4 weeks
description: Assessed via blood sampling
measure: Change in lipid profile
time frame: 0 and 4 weeks
description: Assessed via blood sampling
measure: Change in insulin sensitivity
time frame: 0 and 4 weeks
description: Assessed by HOMA-IR
measure: Change in body composition
time frame: 0 and 4 weeks
description: Assessed by:
DEXA-scan
Anthropometric measurements
measure: Change in quadriceps function
time frame: 0 and 4weeks
description: Assessed by leg dynamometry (Biodex)
measure: Change in blood pressure
time frame: 0 and 4 weeks
description: Measured with a hematometer
measure: Change in heart rate
time frame: 0 and 4 weeks
description: Measured with a hematometer
measure: Medical history
time frame: 0 and 4 weeks
description: Medication use
measure: Physical activity
time frame: 0 and 4 weeks
description: Assessed by:
Accelerometry
Short Questionnaire to Assess Health (SQUASH)
measure: Severity of dyspnea and COPD
time frame: 0 and 4 weeks
description: Assessed by:
Medical Research Council scale (MRC-scale)
COPD assessment test (CAT)
Clinical COPD Questionnaire (CCQ)
measure: Sleep pattern
time frame: 0 and 4 weeks
description: Assess by Pittburgh Sleep Quality Index (PSQI)
measure: Food intake
time frame: 0 and 4 weeks
description: Assessed by food anamnesis questionnaire
measure: Resveratrol and dihydroresveratrol concentrations
time frame: 0 and 4 weeks
description: Assessed by blood sampling
measure: Electrocardiogram
time frame: 0 and 4 weeks
description: Measured with a ECG
measure: Safety parameters
time frame: 0 and 4 weeks
description: Assessed in blood:
Creatinine
Urea
Sodium
Potassium
Gamma-GT
ALAT
ASAT
Alkaline Phosphatase
measure: Baseline lung function
time frame: 0 weeks
description: Assessed by spirometry
arm group label: Resveratrol supplementation
arm group type: Experimental
description: 150 mg of resveratrol for 4 weeks (split over two doses of 75 mg/day)
arm group label: Placebo supplementation
arm group type: Placebo Comparator
description: Placebo for 4 weeks (split over two doses per day)
intervention type: Dietary Supplement
intervention name: Resveratrol
description: 4 weeks of 150 mg resveratrol (2 times 75mg/day)
arm group label: Resveratrol supplementation
other name: resVida (99% pure trans-resveratrol) provided by DSM Nutritional Products, Ltd.
intervention type: Dietary Supplement
intervention name: Placebo
description: 4 weeks of placebo supplementation (two doses per day)
arm group label: Placebo supplementation
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Annemie Schols, Prof.
role: Principal Investigator
affiliation: Maastricht University Medical Center
facility: 
country: Netherlands
citation: 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.
PMID: 22055504
citation: 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.
PMID: 23281350
responsible party type: Sponsor
mesh term: Lung Diseases
mesh term: Lung Diseases, Obstructive
mesh term: Pulmonary Disease, Chronic Obstructive
mesh term: Chronic Disease
mesh term: Resveratrol