<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/NCT01672840</url>
  </required_header>
  <id_info>
    <org_study_id>2012-03</org_study_id>
    <nct_id>NCT01672840</nct_id>
  </id_info>
  <brief_title>Effects of Cocoa on Ambulatory Blood Pressure and Vascular Function in Patients With Stage I Hypertension</brief_title>
  <acronym>DARC</acronym>
  <official_title>Effects of Cocoa on Ambulatory Blood Pressure and Vascular Function in Patients With Stage I Hypertension</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Griffin Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Boston University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Griffin Hospital</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The proposed study Dose And Response to Cocoa (DARC), will examine variation in dose of&#xD;
      cocoa-containing product consumption over an 8-week period and assess effects on blood&#xD;
      pressure, endothelial function and arterial stiffness. The randomized, controlled, modified&#xD;
      Latin square parallel design will compare the effects of two doses of cocoa consumption on&#xD;
      blood pressure, endothelial function and arterial stiffness in 120 adults with stage 1&#xD;
      hypertension.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Hypothesis #1 To verify the efficacy of an 8-week course of cocoa-containing product&#xD;
      consumption on blood pressure in adults with stage 1 hypertension. Specifically, to&#xD;
      demonstrate at least 3.5 mmHg improvement in 24-hour mean systolic blood pressure following 8&#xD;
      weeks of treatment with cocoa- containing products when compared to placebo. Our hypothesis&#xD;
      is that cocoa-containing product consumption will result in clinically significant&#xD;
      improvement of systolic blood pressure at the conclusion of an 8-week course of treatment.&#xD;
&#xD;
      Hypothesis #2 To identify a dose-response relationship in which increasingly higher doses of&#xD;
      cocoa powder in cocoa-containing products will demonstrate correspondingly greater beneficial&#xD;
      effects on blood pressure over an 8-week period in individuals with stage 1 hypertension.&#xD;
      Specifically, to investigate the effects of the variation of dose of cocoa powder in&#xD;
      cocoa-containing products (i.e. 5 grams or 10 grams of cocoa powder) for 8 weeks on blood&#xD;
      pressure. We hypothesize that increasingly higher doses of cocoa powder in cocoa-containing&#xD;
      products will demonstrate correspondingly greater beneficial effects on blood pressure.&#xD;
&#xD;
      Hypothesis #3 To assess the effects of different doses of cocoa-containing product&#xD;
      consumption over an 8-week period on 24-hour diastolic blood pressure, endothelial function,&#xD;
      arterial stiffness, serum lipids, theobromine, CRP, glucose, insulin, body weight, and waist&#xD;
      circumference in adults with stage 1 hypertension. We hypothesize that consumption of&#xD;
      cocoa-containing products will lower diastolic blood pressure; improve endothelial function&#xD;
      of our participants; reduce arterial stiffness; improve serum lipids; theobromine; and will&#xD;
      have no clinically meaningful effects on body weight and waist circumference, CRP, glucose,&#xD;
      or insulin.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>July 2012</start_date>
  <completion_date type="Actual">December 2013</completion_date>
  <primary_completion_date type="Actual">December 2013</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>Treatment</primary_purpose>
    <masking>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Ambulatory Blood Pressure Monitoring (ABPM)</measure>
    <time_frame>8 weeks</time_frame>
    <description>Subjects will undergo 24-hour ambulatory blood pressure monitoring using a FDA approved device (Model 90207 with standard adult cuff or large cuff (depending on arm size), Spacelabs Medical, Inc.). BP will be measured every 30 minutes throughout the 24-hour monitoring period. Mean systolic, mean diastolic, and average mean blood pressure will be calculated from all valid BP measurements. Daytime and nighttime (11:00 PM till 6:30 AM) BP will also be assessed.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Office Blood Pressure</measure>
    <time_frame>8 Weeks</time_frame>
    <description>Systolic and diastolic BP will be measured at each visit using an approved automated device. Blood pressure will be measured (average of three measurements with five minutes between measurements) with the participant sitting in a quiet room.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Flow-mediated dilatation (FMD)</measure>
    <time_frame>8 Weeks</time_frame>
    <description>FMD will be measured as the percent change in brachial artery diameter from pre-cuff inflation to 60-seconds post-cuff release (upper arm cuff position). In addition to brachial diameter at 60 seconds post-cuff release, flow after cuff deflation within the first 15 seconds will be used as an indicator of stimulus strength, hyperemic flow being the stimulus for endothelial reactivity.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Central Aortic Stiffness</measure>
    <time_frame>8 Weeks</time_frame>
    <description>First, we will examine pulse pressure, which reflects central arterial stiffness and is an important predictor of cardiovascular disease mortality in hypertensive subjects. Then, we will use recently developed non-invasive methodology that examines carotid-femoral pulse wave velocity. Carotid femoral pulse wave velocity will be measured using the SphgymoCor (AtCor, Medical, Inc.). This measure will be assessed in a subgroup of the study population (n=50) at the University of Boston site.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Fasting Serum Lipids</measure>
    <time_frame>8 Weeks</time_frame>
    <description>Total cholesterol (Tchol), triglycerides (TG), and high-density lipoprotein (HDL) will be obtained by direct measurements. Very-low-density lipoprotein (VLDL) and low-density-lipoprotein (LDL) will be obtained by calculation: VLDL = TG/5; and LDL = Tchol - (VLDL + HDL). HDL:Tchol ratio will be used to evaluate the impact of treatment assignments on lipid panel.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>C-Reactive Protein (CRP)</measure>
    <time_frame>8 Weeks</time_frame>
    <description>Serum CRP values will be determined using a high sensitivity CRP (hsCRP) ELISA method.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Fasting Glucose and Insulin</measure>
    <time_frame>8 Weeks</time_frame>
    <description>Glucose and insulin will be measured at each time point. HOMA-IR will be calculated.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Body Weight</measure>
    <time_frame>8 Weeks</time_frame>
    <description>Body weight will be measured for all study participants during each visit. Body weight will be measured to the nearest 0.5 pound using a balance-type medical scale. Subjects will be measured in the morning (fasting), unclothed with the exception of undergarments.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Waist Circumference</measure>
    <time_frame>8 Weeks</time_frame>
    <description>Waist circumference will be measured using the U.S. government standard protocol. Waist circumference will be measured around the narrowest point between ribs and hips when viewed from the front after exhaling.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>3- Day Food Diary</measure>
    <time_frame>8 Weeks</time_frame>
    <description>Food diaries will be used to track any variation in the dietary pattern over the course of the study. The study coordinators will instruct participants on how to accurately complete a food diary, and will answer any questions posed by participants at the clinical screening. All participants will be asked to complete food diaries after clinical screening and at the end of each treatment assignment. Diet records will be analyzed by a registered dietitian using basic nutrition and diet analysis software (The Food Processor II, version 7.0; ESHA Research, Salem, OR).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Physical Activity</measure>
    <time_frame>8 Weeks</time_frame>
    <description>Physical activity will be determined by the Seven-Day Physical Activity Recall [PAR]. The PAR provides detail regarding the duration, intensity, and volume (energy expenditure) of physical activity and can therefore be used for a variety of applications. Because it utilizes a one-week time frame, the data from the PAR is often considered representative of typical activity patterns. While it requires considerable cognitive effort by the participants, the interviewer administered version can be completed in a reasonable amount of time (~20 minutes).</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">120</enrollment>
  <condition>Hypertension</condition>
  <arm_group>
    <arm_group_label>5g Cocoa Consumption</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Daily consumption of 10g Extra Dark cholocate and a beverage containing 2.5g of cocoa powder for 8 weeks</description>
  </arm_group>
  <arm_group>
    <arm_group_label>10g Cocoa Consumption</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Daily consumption of 20g Extra Dark cholocate and two beverage containing 2.5g of cocoa powder each for 8 weeks</description>
  </arm_group>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>5g Cocoa Consumption</intervention_name>
    <description>Daily consumption of 10g Extra Dark cholocate and a beverage containing 2.5g of cocoa powder for 8 weeks</description>
    <arm_group_label>5g Cocoa Consumption</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>10g Cocoa Consumption</intervention_name>
    <description>Daily consumption of 20g Extra Dark cholocate and two beverage containing 2.5g of cocoa powder each for 8 weeks</description>
    <arm_group_label>10g Cocoa Consumption</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  men and women age 18-75 years&#xD;
&#xD;
          -  stage 1 hypertension (i.e. 140-159/90-99 mmHg) without anti-hypertensive medication or&#xD;
             with only one anti-hypertensive medicaion&#xD;
&#xD;
          -  body mass index &lt; 35 kg/m²&#xD;
&#xD;
          -  willing to discontinue the use of chocolate/cocoa products at least 4 weeks prior to&#xD;
             intervention.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  anticipated inability to complete or comply with study protocol&#xD;
&#xD;
          -  use of lipid-lowering or aspirin unless stable on medication for at least 1 month and&#xD;
             willing to refrain from taking medication for 12 hours prior to endothelial function&#xD;
             scanning&#xD;
&#xD;
          -  severe hypertension (systolic blood pressure &gt;160mmHg or diastolic blood pressure &gt;100&#xD;
             mmHg), or use more than one anti-hypertensive medications&#xD;
&#xD;
          -  allergic to cocoa products (chocolate or cocoa powder)&#xD;
&#xD;
          -  regular use of vitamin C, vitamin E, fish oil, flax seed oil, omega-3 fatty acids,&#xD;
             Coenzyme Q10, fiber supplements, garlic pills, arginine, red yeast rice, and/or any&#xD;
             kind of antioxidant and unwilling to discontinue supplementation for at least 4 weeks&#xD;
             prior to study initiation and for the study duration. Use of a multi-vitamin&#xD;
             containing no more than two times the recommended daily allowance for vitamins C and E&#xD;
             is permissible&#xD;
&#xD;
          -  diagnosed eating disorder&#xD;
&#xD;
          -  on any specific diet, weight control diet, and/or vegan diet&#xD;
&#xD;
          -  substance abuse (chronic alcoholism and/or other chemical dependency)&#xD;
&#xD;
          -  any unstable medical condition that would limit the ability of a subject to&#xD;
             participate fully in the trial (e.g., cancer, AIDS, tuberculosis, psychotic disorder)&#xD;
&#xD;
          -  current or impending pregnancy. In premenopausal women, pregnancy will be excluded by&#xD;
             pregnancy test at the time of each study visit.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Valentine Njike, MPH, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Yale-Griffin Prevention Research Center</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Joseph A. Vita, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Boston University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Griffin Hospital</name>
      <address>
        <city>Derby</city>
        <state>Connecticut</state>
        <zip>06418</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Boston University School of Medicine</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02118</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>March 2020</verification_date>
  <study_first_submitted>August 22, 2012</study_first_submitted>
  <study_first_submitted_qc>August 22, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 27, 2012</study_first_posted>
  <last_update_submitted>March 25, 2020</last_update_submitted>
  <last_update_submitted_qc>March 25, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">March 26, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Stage 1 Hypertension</keyword>
  <keyword>cocoa consumption</keyword>
  <keyword>Blood pressure</keyword>
  <keyword>Endothelial function</keyword>
  <keyword>arterial stiffness</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Hypertension</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/NCT01672840
org study id: 2012-03
nct id: NCT01672840
lead sponsor: 
collaborator: 
has dmc: No
The proposed study Dose And Response to Cocoa (DARC), will examine variation in dose of
      cocoa-containing product consumption over an 8-week period and assess effects on blood
      pressure, endothelial function and arterial stiffness. The randomized, controlled, modified
      Latin square parallel design will compare the effects of two doses of cocoa consumption on
      blood pressure, endothelial function and arterial stiffness in 120 adults with stage 1
      hypertension.
Hypothesis #1 To verify the efficacy of an 8-week course of cocoa-containing product
      consumption on blood pressure in adults with stage 1 hypertension. Specifically, to
      demonstrate at least 3.5 mmHg improvement in 24-hour mean systolic blood pressure following 8
      weeks of treatment with cocoa- containing products when compared to placebo. Our hypothesis
      is that cocoa-containing product consumption will result in clinically significant
      improvement of systolic blood pressure at the conclusion of an 8-week course of treatment.

      Hypothesis #2 To identify a dose-response relationship in which increasingly higher doses of
      cocoa powder in cocoa-containing products will demonstrate correspondingly greater beneficial
      effects on blood pressure over an 8-week period in individuals with stage 1 hypertension.
      Specifically, to investigate the effects of the variation of dose of cocoa powder in
      cocoa-containing products (i.e. 5 grams or 10 grams of cocoa powder) for 8 weeks on blood
      pressure. We hypothesize that increasingly higher doses of cocoa powder in cocoa-containing
      products will demonstrate correspondingly greater beneficial effects on blood pressure.

      Hypothesis #3 To assess the effects of different doses of cocoa-containing product
      consumption over an 8-week period on 24-hour diastolic blood pressure, endothelial function,
      arterial stiffness, serum lipids, theobromine, CRP, glucose, insulin, body weight, and waist
      circumference in adults with stage 1 hypertension. We hypothesize that consumption of
      cocoa-containing products will lower diastolic blood pressure; improve endothelial function
      of our participants; reduce arterial stiffness; improve serum lipids; theobromine; and will
      have no clinically meaningful effects on body weight and waist circumference, CRP, glucose,
      or insulin.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Double (Participant, Investigator)
measure: Ambulatory Blood Pressure Monitoring (ABPM)
time frame: 8 weeks
description: Subjects will undergo 24-hour ambulatory blood pressure monitoring using a FDA approved device (Model 90207 with standard adult cuff or large cuff (depending on arm size), Spacelabs Medical, Inc.). BP will be measured every 30 minutes throughout the 24-hour monitoring period. Mean systolic, mean diastolic, and average mean blood pressure will be calculated from all valid BP measurements. Daytime and nighttime (11:00 PM till 6:30 AM) BP will also be assessed.
measure: Office Blood Pressure
time frame: 8 Weeks
description: Systolic and diastolic BP will be measured at each visit using an approved automated device. Blood pressure will be measured (average of three measurements with five minutes between measurements) with the participant sitting in a quiet room.
measure: Flow-mediated dilatation (FMD)
time frame: 8 Weeks
description: FMD will be measured as the percent change in brachial artery diameter from pre-cuff inflation to 60-seconds post-cuff release (upper arm cuff position). In addition to brachial diameter at 60 seconds post-cuff release, flow after cuff deflation within the first 15 seconds will be used as an indicator of stimulus strength, hyperemic flow being the stimulus for endothelial reactivity.
measure: Central Aortic Stiffness
time frame: 8 Weeks
description: First, we will examine pulse pressure, which reflects central arterial stiffness and is an important predictor of cardiovascular disease mortality in hypertensive subjects. Then, we will use recently developed non-invasive methodology that examines carotid-femoral pulse wave velocity. Carotid femoral pulse wave velocity will be measured using the SphgymoCor (AtCor, Medical, Inc.). This measure will be assessed in a subgroup of the study population (n=50) at the University of Boston site.
measure: Fasting Serum Lipids
time frame: 8 Weeks
description: Total cholesterol (Tchol), triglycerides (TG), and high-density lipoprotein (HDL) will be obtained by direct measurements. Very-low-density lipoprotein (VLDL) and low-density-lipoprotein (LDL) will be obtained by calculation: VLDL = TG/5; and LDL = Tchol - (VLDL + HDL). HDL:Tchol ratio will be used to evaluate the impact of treatment assignments on lipid panel.
measure: C-Reactive Protein (CRP)
time frame: 8 Weeks
description: Serum CRP values will be determined using a high sensitivity CRP (hsCRP) ELISA method.
measure: Fasting Glucose and Insulin
time frame: 8 Weeks
description: Glucose and insulin will be measured at each time point. HOMA-IR will be calculated.
measure: Body Weight
time frame: 8 Weeks
description: Body weight will be measured for all study participants during each visit. Body weight will be measured to the nearest 0.5 pound using a balance-type medical scale. Subjects will be measured in the morning (fasting), unclothed with the exception of undergarments.
measure: Waist Circumference
time frame: 8 Weeks
description: Waist circumference will be measured using the U.S. government standard protocol. Waist circumference will be measured around the narrowest point between ribs and hips when viewed from the front after exhaling.
measure: 3- Day Food Diary
time frame: 8 Weeks
description: Food diaries will be used to track any variation in the dietary pattern over the course of the study. The study coordinators will instruct participants on how to accurately complete a food diary, and will answer any questions posed by participants at the clinical screening. All participants will be asked to complete food diaries after clinical screening and at the end of each treatment assignment. Diet records will be analyzed by a registered dietitian using basic nutrition and diet analysis software (The Food Processor II, version 7.0; ESHA Research, Salem, OR).
measure: Physical Activity
time frame: 8 Weeks
description: Physical activity will be determined by the Seven-Day Physical Activity Recall [PAR]. The PAR provides detail regarding the duration, intensity, and volume (energy expenditure) of physical activity and can therefore be used for a variety of applications. Because it utilizes a one-week time frame, the data from the PAR is often considered representative of typical activity patterns. While it requires considerable cognitive effort by the participants, the interviewer administered version can be completed in a reasonable amount of time (~20 minutes).
arm group label: 5g Cocoa Consumption
arm group type: Experimental
description: Daily consumption of 10g Extra Dark cholocate and a beverage containing 2.5g of cocoa powder for 8 weeks
arm group label: 10g Cocoa Consumption
arm group type: Experimental
description: Daily consumption of 20g Extra Dark cholocate and two beverage containing 2.5g of cocoa powder each for 8 weeks
intervention type: Dietary Supplement
intervention name: 5g Cocoa Consumption
description: Daily consumption of 10g Extra Dark cholocate and a beverage containing 2.5g of cocoa powder for 8 weeks
arm group label: 5g Cocoa Consumption
intervention type: Dietary Supplement
intervention name: 10g Cocoa Consumption
description: Daily consumption of 20g Extra Dark cholocate and two beverage containing 2.5g of cocoa powder each for 8 weeks
arm group label: 10g Cocoa Consumption
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: No
last name: Valentine Njike, MPH, MD
role: Principal Investigator
affiliation: Yale-Griffin Prevention Research Center
last name: Joseph A. Vita, MD
role: Principal Investigator
affiliation: Boston University
facility: 
facility: 
country: United States
responsible party type: Sponsor
mesh term: Hypertension