<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/NCT01671514</url>
  </required_header>
  <id_info>
    <org_study_id>UCSD IRB 111680</org_study_id>
    <nct_id>NCT01671514</nct_id>
  </id_info>
  <brief_title>Effects of Dark Chocolate on Exercise Capacity, and Mitochondrial Structure and Function</brief_title>
  <official_title>Effects of Epicatechin-enriched Dark Chocolate on Mitochondrial Function and Exercise Capacity in Patients With Both Diabetes and Heart Failure and in Sedentary Individuals</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of California, San Diego</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>The Hershey Company</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>University of California, San Diego</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The major goal of this study is to characterize the ability of dark chocolate enriched in&#xD;
      epicatechin (a component of dark chocolate) to improve the structural and functional features&#xD;
      of mitochondria in two groups&#xD;
&#xD;
        1. Patients with heart failure (HF) and type 2 diabetes (DM2) and&#xD;
&#xD;
        2. Normal yet sedentary individuals with impaired baseline exercise capacity (as assessed&#xD;
           by VO2 max)&#xD;
&#xD;
      We propose that a 3 month treatment with dark chocolate will lead to a significant&#xD;
      improvement in exercise capacity which will be secondary to the improvement in skeletal&#xD;
      muscle structure from epicatechin.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The flavanol epicatechin (which is derived from cocoa and has no known toxicity in humans)&#xD;
      has been shown in clinical trials to increase levels of nitric oxide (NO) as assessed by&#xD;
      flow-mediated dilation (FMD) in the brachial artery and measurements of circulating NO in&#xD;
      plasma. NO is thought to be an activator of PGC-1 alpha [PPAR (peroxisome&#xD;
      proliferator-activated receptor) alpha coactivator 1] which stimulates mitochondrial&#xD;
      biogenesis. In both patients with heart failure and diabetes there is nitric oxide deficiency&#xD;
      and mitochondrial dysfunction. In our proposed double-blinded placebo controlled clinical&#xD;
      trial, we will test the hypothesis that chronic administration of epicatechin to patients&#xD;
      with both heart failure and diabetes will increase levels of NO and PGC-1 alpha leading to&#xD;
      increased mitochondrial biogenesis and improved mitochondrial function. We believe similar&#xD;
      changes will occur in sedentary individuals.&#xD;
&#xD;
      In a preliminary study with 5 patients with heart failure and diabetes (conducted under UCSD&#xD;
      IRB protocol number #090688) we have shown that epicatechin enriched dark chocolate improves&#xD;
      mitochondrial structure (Taub PR, Ramirez-Sanchez I, Ciaraldi TP, et al. Alterations in&#xD;
      Skeletal Muscle Indicators of Mitochondrial Structure and Biogenesis in Patients with Type 2&#xD;
      Diabetes and Heart Failure: Effects of Epicatechin Rich Cocoa. Clin Transl Sci.&#xD;
      2011;5(1):43-47.)&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>July 2012</start_date>
  <completion_date type="Actual">December 2014</completion_date>
  <primary_completion_date type="Actual">December 2014</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>
    <masking>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change from baseline in exercise capacity</measure>
    <time_frame>Baseline and 3 months</time_frame>
    <description>Objectively evaluate exercise capacity through cycle ergometry to measure VO2 max.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change from baseline in skeletal muscle metabolism</measure>
    <time_frame>Baseline and 3 months</time_frame>
    <description>The change in skeletal muscle metabolism will be evaluated by magnetic resonance spectroscopy</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change from baseline in pre-specified biomarker levels in blood, skeletal muscle, and urine</measure>
    <time_frame>Baseline and 3 months</time_frame>
    <description>Skeletal muscle biopsies and blood draws will be performed to obtain experimental samples.</description>
  </primary_outcome>
  <other_outcome>
    <measure>Change from baseline in quality of life, health, and nutrition questionnaires</measure>
    <time_frame>Baseline and 3 months</time_frame>
    <description>Specific questionnaires utilized include SF-36 questionnaire, Morisky Medication Adherence Scale (MMAS-8) questionnaire, the Minnesota Living with Heart Failure scale (MLHFQ), the Physical Activity Enjoyment Scale (PACES), the Leisure Time Exercise questionnaire (LTE), the Multidimensional Fatigue Symptom Inventory (MFSI) and the Block Questionnaires for Dietary Fat Screening and Fruit/Vegetable/Fiber Screening</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">21</enrollment>
  <condition>Heart Failure</condition>
  <condition>Type 2 Diabetes</condition>
  <arm_group>
    <arm_group_label>Sedentary</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>The sedentary arm will be randomly assigned to either epicatechin-enriched dark chocolate or low-epicatechin dark chocolate as a placebo. Participants will take one square of chocolate per day for 90 days.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Heart failure/diabetes</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>The heart failure/diabetes arm will be randomly assigned to either epicatechin-enriched dark chocolate or low-epicatechin dark chocolate as a placebo. Participants will take one square of chocolate per day for 90 days.</description>
  </arm_group>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Epicatechin-enriched dark chocolate</intervention_name>
    <description>For experimental purposes, subjects will take one square of epicatechin-enriched dark chocolate per day for 90 days.</description>
    <arm_group_label>Heart failure/diabetes</arm_group_label>
    <arm_group_label>Sedentary</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Low-epicatechin dark chocolate</intervention_name>
    <description>As a placebo control, subjects will take 1 square of low-epicatechin chocolate per day for 90 days.</description>
    <arm_group_label>Heart failure/diabetes</arm_group_label>
    <arm_group_label>Sedentary</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Healthy, sedentary individuals:&#xD;
&#xD;
        Inclusion Criteria:&#xD;
&#xD;
          -  Healthy, inactive individuals&#xD;
&#xD;
          -  BMI 27-32&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Smoking or quit smoking less than 1 year prior to enrollment&#xD;
&#xD;
          -  Currently taking Coumadin or Pradaxa.&#xD;
&#xD;
        Heart failure and diabetes patients:&#xD;
&#xD;
        Inclusion Criteria:&#xD;
&#xD;
          -  Medically diagnosed with heart failure and diabetes&#xD;
&#xD;
          -  No significant HbA1C fluctuations in past 6 months&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Currently taking Insulin&#xD;
&#xD;
          -  Currently taking Coumadin or Pradaxa.&#xD;
&#xD;
          -  Smoking or quit smoking less than 1 year prior to enrollment&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>40 Years</minimum_age>
    <maximum_age>70 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Pam Taub, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Assistant Professor of Medicine, University of California, San Diego</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of California, San Diego</name>
      <address>
        <city>La Jolla</city>
        <state>California</state>
        <zip>92093</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <reference>
    <citation>Taub PR, Ramirez-Sanchez I, Ciaraldi TP, Perkins G, Murphy AN, Naviaux R, Hogan M, Maisel AS, Henry RR, Ceballos G, Villarreal F. Alterations in skeletal muscle indicators of mitochondrial structure and biogenesis in patients with type 2 diabetes and heart failure: effects of epicatechin rich cocoa. Clin Transl Sci. 2012 Feb;5(1):43-7. doi: 10.1111/j.1752-8062.2011.00357.x. Epub 2011 Nov 7.</citation>
    <PMID>22376256</PMID>
  </reference>
  <verification_date>June 2015</verification_date>
  <study_first_submitted>August 20, 2012</study_first_submitted>
  <study_first_submitted_qc>August 22, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 23, 2012</study_first_posted>
  <last_update_submitted>June 1, 2015</last_update_submitted>
  <last_update_submitted_qc>June 1, 2015</last_update_submitted_qc>
  <last_update_posted type="Estimate">June 3, 2015</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of California, San Diego</investigator_affiliation>
    <investigator_full_name>Pam Taub, MD</investigator_full_name>
    <investigator_title>Assistant Professor of Medicine</investigator_title>
  </responsible_party>
  <keyword>mitochondrial biogenesis</keyword>
  <keyword>skeletal muscle</keyword>
  <keyword>epicatechin</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Heart Failure</mesh_term>
  </condition_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/NCT01671514
org study id: UCSD IRB 111680
nct id: NCT01671514
lead sponsor: 
collaborator: 
has dmc: Yes
The major goal of this study is to characterize the ability of dark chocolate enriched in
      epicatechin (a component of dark chocolate) to improve the structural and functional features
      of mitochondria in two groups

        1. Patients with heart failure (HF) and type 2 diabetes (DM2) and

        2. Normal yet sedentary individuals with impaired baseline exercise capacity (as assessed
           by VO2 max)

      We propose that a 3 month treatment with dark chocolate will lead to a significant
      improvement in exercise capacity which will be secondary to the improvement in skeletal
      muscle structure from epicatechin.
The flavanol epicatechin (which is derived from cocoa and has no known toxicity in humans)
      has been shown in clinical trials to increase levels of nitric oxide (NO) as assessed by
      flow-mediated dilation (FMD) in the brachial artery and measurements of circulating NO in
      plasma. NO is thought to be an activator of PGC-1 alpha [PPAR (peroxisome
      proliferator-activated receptor) alpha coactivator 1] which stimulates mitochondrial
      biogenesis. In both patients with heart failure and diabetes there is nitric oxide deficiency
      and mitochondrial dysfunction. In our proposed double-blinded placebo controlled clinical
      trial, we will test the hypothesis that chronic administration of epicatechin to patients
      with both heart failure and diabetes will increase levels of NO and PGC-1 alpha leading to
      increased mitochondrial biogenesis and improved mitochondrial function. We believe similar
      changes will occur in sedentary individuals.

      In a preliminary study with 5 patients with heart failure and diabetes (conducted under UCSD
      IRB protocol number #090688) we have shown that epicatechin enriched dark chocolate improves
      mitochondrial structure (Taub PR, Ramirez-Sanchez I, Ciaraldi TP, et al. Alterations in
      Skeletal Muscle Indicators of Mitochondrial Structure and Biogenesis in Patients with Type 2
      Diabetes and Heart Failure: Effects of Epicatechin Rich Cocoa. Clin Transl Sci.
      2011;5(1):43-47.)
allocation: Randomized
intervention model: Parallel Assignment
masking: Double (Participant, Investigator)
measure: Change from baseline in exercise capacity
time frame: Baseline and 3 months
description: Objectively evaluate exercise capacity through cycle ergometry to measure VO2 max.
measure: Change from baseline in skeletal muscle metabolism
time frame: Baseline and 3 months
description: The change in skeletal muscle metabolism will be evaluated by magnetic resonance spectroscopy
measure: Change from baseline in pre-specified biomarker levels in blood, skeletal muscle, and urine
time frame: Baseline and 3 months
description: Skeletal muscle biopsies and blood draws will be performed to obtain experimental samples.
measure: Change from baseline in quality of life, health, and nutrition questionnaires
time frame: Baseline and 3 months
description: Specific questionnaires utilized include SF-36 questionnaire, Morisky Medication Adherence Scale (MMAS-8) questionnaire, the Minnesota Living with Heart Failure scale (MLHFQ), the Physical Activity Enjoyment Scale (PACES), the Leisure Time Exercise questionnaire (LTE), the Multidimensional Fatigue Symptom Inventory (MFSI) and the Block Questionnaires for Dietary Fat Screening and Fruit/Vegetable/Fiber Screening
arm group label: Sedentary
arm group type: Experimental
description: The sedentary arm will be randomly assigned to either epicatechin-enriched dark chocolate or low-epicatechin dark chocolate as a placebo. Participants will take one square of chocolate per day for 90 days.
arm group label: Heart failure/diabetes
arm group type: Experimental
description: The heart failure/diabetes arm will be randomly assigned to either epicatechin-enriched dark chocolate or low-epicatechin dark chocolate as a placebo. Participants will take one square of chocolate per day for 90 days.
intervention type: Dietary Supplement
intervention name: Epicatechin-enriched dark chocolate
description: For experimental purposes, subjects will take one square of epicatechin-enriched dark chocolate per day for 90 days.
arm group label: Heart failure/diabetes
arm group label: Sedentary
intervention type: Other
intervention name: Low-epicatechin dark chocolate
description: As a placebo control, subjects will take 1 square of low-epicatechin chocolate per day for 90 days.
arm group label: Heart failure/diabetes
arm group label: Sedentary
criteria: 
gender: All
minimum age: 40 Years
maximum age: 70 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Pam Taub, MD
role: Principal Investigator
affiliation: Assistant Professor of Medicine, University of California, San Diego
facility: 
country: United States
citation: Taub PR, Ramirez-Sanchez I, Ciaraldi TP, Perkins G, Murphy AN, Naviaux R, Hogan M, Maisel AS, Henry RR, Ceballos G, Villarreal F. Alterations in skeletal muscle indicators of mitochondrial structure and biogenesis in patients with type 2 diabetes and heart failure: effects of epicatechin rich cocoa. Clin Transl Sci. 2012 Feb;5(1):43-7. doi: 10.1111/j.1752-8062.2011.00357.x. Epub 2011 Nov 7.
PMID: 22376256
responsible party type: Principal Investigator
investigator affiliation: University of California, San Diego
investigator full name: Pam Taub, MD
investigator title: Assistant Professor of Medicine
mesh term: Heart Failure