<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/NCT03815162</url>
  </required_header>
  <id_info>
    <org_study_id>112-1809</org_study_id>
    <nct_id>NCT03815162</nct_id>
  </id_info>
  <brief_title>Cocoa Flavanol Supplementation in Raynaud's Phenomenon</brief_title>
  <official_title>Pilot Study to Investigate the Effect of Cocoa Flavanols on Symptoms in Primary Raynaud's Phenomenon</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Nottingham</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Nottingham</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The study aims to investigate the effect that supplementing the diet with cocoa flavanols has&#xD;
      on vasospasm symptoms and temperature regulation in women with primary Raynaud's phenomenon&#xD;
      (PRP). Participants will be randomised to consume either high flavanol cocoa extract or low&#xD;
      flavanol cocoa (placebo) daily for 3 months.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Primary Raynaud's phenomenon (PRP) is characterised by periodic vasospasm of the fingers and&#xD;
      toes precipitated by exposure to cold or emotional stimuli and stress. Previous studies have&#xD;
      demonstrated that underlying this condition there can be vascular endothelium dysfunction.&#xD;
      Pharmacological interventions used to relieve symptoms and complications in PRP include drugs&#xD;
      targeted at increasing nitric oxide (NO; transdermal nitrates) levels. Cocoa derived&#xD;
      products, rich in the phytonutrients 'flavanols', have been shown to increase the&#xD;
      bioavailability of NO at the vascular endothelium and promote vasodilation, which may address&#xD;
      an underlying cause of PRP and mitigate symptoms. Previous work carried out in the research&#xD;
      group has indicated that the acute consumption of cocoa does not compromise the&#xD;
      counter-regulatory responses to localised cold exposure in those with PRP.&#xD;
&#xD;
      30 individuals with PRP will be recruited. Those interested in taking part will attend a&#xD;
      medical screening and consent visit. If recruited, a participant number will be assigned to&#xD;
      them sequentially and they will be randomised to either experimental or control group, with&#xD;
      neither the participants nor the research team knowing which group they have been allocated&#xD;
      to. Participants will be asked to complete a diet diary before attending 4 further visits&#xD;
      over a period of 3 months.&#xD;
&#xD;
      Visit 1 (pre-intervention) and 4 (end of intervention); immediately on arrival, participants&#xD;
      will be asked to lie semi-supine on a hospital bed. Skin temperature (surface thermocouples)&#xD;
      and 'core' temperature (infrared tympanic thermometer) will start to be recorded to identify&#xD;
      when these parameters have stabilized in room temperature (set at 25oC). Blood pressure will&#xD;
      be taken using an arm cuff. Then a Finometer cuff will be attached to the left middle finger&#xD;
      to record cardiovascular parameters (Blood pressure /heart rate/ cardiac output) and a laser&#xD;
      Doppler probe will be attached to the dorsum of both index fingers to assess skin blood flow.&#xD;
      Once the finger skin temperature has remained stable for 6 minutes, baseline Finometer and&#xD;
      laser Doppler measurements will be recorded and the skin and 'core' temperature will be&#xD;
      noted. Then, the right hand will be placed in a temperature regulated box which is set at an&#xD;
      air temperature of 0oC. The hand will be cooled to a finger skin temperature of 15oC, then&#xD;
      the box temperature will be modified to maintain the skin temperature at 15oC. The time that&#xD;
      it takes for the skin temperature on the fingers to reach 15oC will be recorded. With the&#xD;
      finger skin temperature stable at 15oC, Finometer and laser Doppler measurements will be&#xD;
      repeated and the 'core' temperature at this point noted. Then, the hand will be removed from&#xD;
      the chamber, and allowed to equilibrate in room temperature. The time taken for the skin&#xD;
      temperature to reach stability will be recorded, as will the absolute temperature that it&#xD;
      stabilises to. Measures above will be repeated once hand temperature is stable. Once these&#xD;
      measures have been made, all equipment will be removed and a 15ml blood sample will be taken&#xD;
      (for epicatechin, glucose and insulin analysis). The participant will be asked to complete 3&#xD;
      questionnaires (SF-36, Raynaud's symptoms and a food frequency questionnaire). Participants&#xD;
      will also return a 4-day diet diary at visits 1 and 4, and their symptom diary at visit 4.&#xD;
&#xD;
      Visits 2 (end of month 1) and 3 (end of month 2); participants will return a 4-day diet&#xD;
      diary, symptom diary and any unused capsules. They will also have a resting blood pressure&#xD;
      measurement made, weight measured and be asked to complete 3 questionnaires (SF-36, Raynaud's&#xD;
      symptoms and a food frequency questionnaire).&#xD;
&#xD;
      At the end of Visits 1, 2 and 3, participants will be given a months' supply of capsules, a&#xD;
      symptom diary and a diet diary (to be completed in the week prior to the next visit).&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">October 16, 2018</start_date>
  <completion_date type="Actual">July 31, 2021</completion_date>
  <primary_completion_date type="Actual">April 30, 2020</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>
    <intervention_model_description>Double-blinded, placebo controlled study. Block randomised with equal allocation of participants between groups.</intervention_model_description>
    <primary_purpose>Prevention</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
    <masking_description>Opaque capsules of equal size and appearance presented in similar bottles labelled only by a code. Code to product information is held by the manufacturer and un-blinding of the PI will only occur once the study analysis has been completed or in the event of a serious adverse event occurring.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Vasospasm</measure>
    <time_frame>3 months</time_frame>
    <description>frequency of vasospasm</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Severity of vasospasm symptoms</measure>
    <time_frame>3 months</time_frame>
    <description>visual analogue score for pain associated with each vasospasm occasion. Participants indicate pain intensity by placing a vertical line on a 100mm horizontal line where the start of the line (left-hand side; 0mm) represents 'no pain' and the end of the line (right-hand side; 100mm) represents 'most severe pain'. Distance of the vertical line from 0 provides the visual analogue score. A lower score indicates a more favourable outcome.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of vasospasm symptoms</measure>
    <time_frame>3 months</time_frame>
    <description>duration that symptoms persist for on each vasospasm occasion</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Raynaud's Condition score</measure>
    <time_frame>3 months</time_frame>
    <description>Assessment of Raynaud's symptoms using the validated Raynaud's Condition Score. This is a 1 to 10 Likert scale, with 0 representing 'no difficulty' and 10 indicating 'extreme difficulty' with symptoms; collected daily for 3 months, a lower score indicates a more favourable outcome.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Blood pressure</measure>
    <time_frame>pre-intervention</time_frame>
    <description>blood pressure measured by automated oscillometric blood pressure</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Blood pressure</measure>
    <time_frame>4 weeks after starting intervention</time_frame>
    <description>blood pressure measured by automated oscillometric blood pressure</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Blood pressure</measure>
    <time_frame>8 weeks after starting intervention</time_frame>
    <description>blood pressure measured by automated oscillometric blood pressure</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Blood pressure</measure>
    <time_frame>12 weeks after starting the intervention</time_frame>
    <description>blood pressure measured by automated oscillometric blood pressure</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Dietary polyphenol intake</measure>
    <time_frame>pre-intervention</time_frame>
    <description>estimation of dietary polyphenols made by food frequency questionnaire</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Dietary polyphenol intake</measure>
    <time_frame>4 weeks after starting intervention</time_frame>
    <description>estimation of dietary polyphenols made by food frequency questionnaire</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Dietary polyphenol intake</measure>
    <time_frame>8 weeks after starting intervention</time_frame>
    <description>estimation of dietary polyphenols made by food frequency questionnaire</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Dietary polyphenol intake</measure>
    <time_frame>12 weeks after starting the intervention</time_frame>
    <description>estimation of dietary polyphenols made by food frequency questionnaire</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Ambient skin temperature</measure>
    <time_frame>pre-intervention</time_frame>
    <description>skin temperature of a finger exposed to an environmental temperature of 25oC, before cooling</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Ambient skin temperature</measure>
    <time_frame>12 weeks after starting the intervention</time_frame>
    <description>skin temperature of a finger exposed to an environmental temperature of 25oC, before cooling</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Ambient skin blood flow</measure>
    <time_frame>pre-intervention</time_frame>
    <description>finger blood flow (measured using laser Doppler flowmetry) when exposed to an environmental temperature of 25oC, before cooling</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Ambient skin blood flow</measure>
    <time_frame>12 weeks after starting the intervention</time_frame>
    <description>finger blood flow (measured using laser Doppler flowmetry) when exposed to an environmental temperature of 25oC, before cooling</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Skin temperature response to acute cooling</measure>
    <time_frame>pre-intervention</time_frame>
    <description>The time taken for skin temperature of the finger to stabilise in response to localised cooling (in an air temperature of 0oC)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Skin temperature response to acute cooling</measure>
    <time_frame>12 weeks after starting the intervention</time_frame>
    <description>The time taken for skin temperature of the finger to stabilise in response to localised cooling (in an air temperature of 0oC)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Skin blood flow response to acute cooling</measure>
    <time_frame>pre-intervention</time_frame>
    <description>Finger Skin blood flow; measurement (using laser Doppler flowmetry) made once finger skin temperature has stabilised in response to localised cooling (in an air temperature of 0oC)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Skin blood flow response to acute cooling</measure>
    <time_frame>12 weeks after starting the intervention</time_frame>
    <description>Finger Skin blood flow; measurement (using laser Doppler flowmetry) made once finger skin temperature has stabilised in response to localised cooling (in an air temperature of 0oC)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Skin temperature response to re-warming</measure>
    <time_frame>pre-intervention</time_frame>
    <description>The time taken for skin temperature of finger to stabilise in an environmental temperature of 25oC following localised cooling (in an air temperature of 0oC)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Skin temperature response to re-warming</measure>
    <time_frame>12 weeks after starting the intervention</time_frame>
    <description>The time taken for skin temperature of finger to stabilise in an environmental temperature of 25oC following localised cooling (in an air temperature of 0oC)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Skin temperature after re-warming</measure>
    <time_frame>pre-intervention</time_frame>
    <description>skin temperature that a finger exposed to an environmental temperature of 25oC stabilises to after localised cooling</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Skin temperature after re-warming</measure>
    <time_frame>12 weeks after starting the intervention</time_frame>
    <description>skin temperature that a finger exposed to an environmental temperature of 25oC stabilises to after localised cooling</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Quality of life score</measure>
    <time_frame>pre-intervention</time_frame>
    <description>Assessed using SF-36 questionnaire. Responses are coded and normalised to the UK population, as per standard methods, and a score for mental and physical health calculated; a higher score indicating a more favourable outcome</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Quality of life score</measure>
    <time_frame>4 weeks after starting intervention</time_frame>
    <description>Assessed using SF-36 questionnaire. Responses are coded and normalised to the UK population, as per standard methods, and a score for mental and physical health calculated; a higher score indicating a more favourable outcome</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Quality of life score</measure>
    <time_frame>8 weeks after starting intervention</time_frame>
    <description>Assessed using SF-36 questionnaire. Responses are coded and normalised to the UK population, as per standard methods, and a score for mental and physical health calculated; a higher score indicating a more favourable outcome</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Quality of life score</measure>
    <time_frame>12 weeks after starting the intervention</time_frame>
    <description>Assessed using SF-36 questionnaire. Responses are coded and normalised to the UK population, as per standard methods, and a score for mental and physical health calculated; a higher score indicating a more favourable outcome</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Attrition rate</measure>
    <time_frame>2 years</time_frame>
    <description>Number of participants completing the protocol as a proportion of those who were randomised to the study</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Adverse events</measure>
    <time_frame>3 months</time_frame>
    <description>Any injury, accident or illness experienced over the intervention period will be documented</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Recruitment rate</measure>
    <time_frame>2 years</time_frame>
    <description>number of people volunteering to take part in the study as a proportion of those expressing initial interest</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">27</enrollment>
  <condition>Primary Raynaud Phenomenon</condition>
  <arm_group>
    <arm_group_label>High Flavanol Cocoa extract</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>278mg total flavanols (38.3mg epicatechin) per opaque cellulose capsule 3 capsules consumed once per day (836 mg total flavanols; 115mg epicatechin) for 3 months</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Alkalised cocoa</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>0mg total flavanols (0mg epicatechin) per opaque cellulose capsule 3 capsules consumed once per day (0mg total flavanols; 0mg epicatechin) for 3 months</description>
  </arm_group>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>High Flavanol Cocoa extract</intervention_name>
    <description>Experimental group</description>
    <arm_group_label>High Flavanol Cocoa extract</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Alkalised cocoa</intervention_name>
    <description>Control group</description>
    <arm_group_label>Alkalised cocoa</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Experience symptoms of Primary Raynaud's Phenomenon, with &gt;1 attack / week through the&#xD;
             winter months&#xD;
&#xD;
          -  Daily consumption of caffeine containing foods/drinks.&#xD;
&#xD;
          -  BMI &lt;27kg/m2&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  pregnant or breast feeding (women only),&#xD;
&#xD;
          -  clinically significant metabolic or endocrine abnormalities&#xD;
&#xD;
          -  fasting glucose &gt;6.5mmol/l,&#xD;
&#xD;
          -  taking Bosentan, aspirin, dipyridamole, heparin or transdermal nitrates,&#xD;
&#xD;
          -  herbal supplement use,&#xD;
&#xD;
          -  food allergies related to the investigational product (cocoa, peanuts, milk),&#xD;
&#xD;
          -  sensitivity to methylxanthines (e.g. caffeine, theobromine).&#xD;
&#xD;
          -  Presence or history of digital ulceration,&#xD;
&#xD;
          -  blood parameters suggesting secondary Raynaud's,&#xD;
&#xD;
          -  history of migraines&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>60 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Ian A Macdonald, PhD</last_name>
    <role>Study Director</role>
    <affiliation>University of Nottingham</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>David Greenfield Human Physiology Laboratories</name>
      <address>
        <city>Nottingham</city>
        <state>Notts</state>
        <zip>NG72UH</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United Kingdom</country>
  </location_countries>
  <reference>
    <citation>Herrick A. Raynaud's phenomenon. Curr Treat Options Cardiovasc Med. 2008 Apr;10(2):146-55. doi: 10.1007/s11936-008-0016-y.</citation>
    <PMID>18325317</PMID>
  </reference>
  <reference>
    <citation>Chung L, Shapiro L, Fiorentino D, Baron M, Shanahan J, Sule S, Hsu V, Rothfield N, Steen V, Martin RW, Smith E, Mayes M, Simms R, Pope J, Kahaleh B, Csuka ME, Gruber B, Collier D, Sweiss N, Gilbert A, Dechow FJ, Gregory J, Wigley FM. MQX-503, a novel formulation of nitroglycerin, improves the severity of Raynaud's phenomenon: a randomized, controlled trial. Arthritis Rheum. 2009 Mar;60(3):870-7. doi: 10.1002/art.24351.</citation>
    <PMID>19248104</PMID>
  </reference>
  <verification_date>November 2021</verification_date>
  <study_first_submitted>January 18, 2019</study_first_submitted>
  <study_first_submitted_qc>January 21, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 24, 2019</study_first_posted>
  <last_update_submitted>November 3, 2021</last_update_submitted>
  <last_update_submitted_qc>November 3, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">November 4, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Nottingham</investigator_affiliation>
    <investigator_full_name>Elizabeth Simpson</investigator_full_name>
    <investigator_title>Senior Research Fellow</investigator_title>
  </responsible_party>
  <keyword>cocoa flavanols</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Raynaud Disease</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
    <ipd_description>Individual data will not be shared with other researchers</ipd_description>
  </patient_data>
  <!-- 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/NCT03815162
org study id: 112-1809
nct id: NCT03815162
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
The study aims to investigate the effect that supplementing the diet with cocoa flavanols has
      on vasospasm symptoms and temperature regulation in women with primary Raynaud's phenomenon
      (PRP). Participants will be randomised to consume either high flavanol cocoa extract or low
      flavanol cocoa (placebo) daily for 3 months.
Primary Raynaud's phenomenon (PRP) is characterised by periodic vasospasm of the fingers and
      toes precipitated by exposure to cold or emotional stimuli and stress. Previous studies have
      demonstrated that underlying this condition there can be vascular endothelium dysfunction.
      Pharmacological interventions used to relieve symptoms and complications in PRP include drugs
      targeted at increasing nitric oxide (NO; transdermal nitrates) levels. Cocoa derived
      products, rich in the phytonutrients 'flavanols', have been shown to increase the
      bioavailability of NO at the vascular endothelium and promote vasodilation, which may address
      an underlying cause of PRP and mitigate symptoms. Previous work carried out in the research
      group has indicated that the acute consumption of cocoa does not compromise the
      counter-regulatory responses to localised cold exposure in those with PRP.

      30 individuals with PRP will be recruited. Those interested in taking part will attend a
      medical screening and consent visit. If recruited, a participant number will be assigned to
      them sequentially and they will be randomised to either experimental or control group, with
      neither the participants nor the research team knowing which group they have been allocated
      to. Participants will be asked to complete a diet diary before attending 4 further visits
      over a period of 3 months.

      Visit 1 (pre-intervention) and 4 (end of intervention); immediately on arrival, participants
      will be asked to lie semi-supine on a hospital bed. Skin temperature (surface thermocouples)
      and 'core' temperature (infrared tympanic thermometer) will start to be recorded to identify
      when these parameters have stabilized in room temperature (set at 25oC). Blood pressure will
      be taken using an arm cuff. Then a Finometer cuff will be attached to the left middle finger
      to record cardiovascular parameters (Blood pressure /heart rate/ cardiac output) and a laser
      Doppler probe will be attached to the dorsum of both index fingers to assess skin blood flow.
      Once the finger skin temperature has remained stable for 6 minutes, baseline Finometer and
      laser Doppler measurements will be recorded and the skin and 'core' temperature will be
      noted. Then, the right hand will be placed in a temperature regulated box which is set at an
      air temperature of 0oC. The hand will be cooled to a finger skin temperature of 15oC, then
      the box temperature will be modified to maintain the skin temperature at 15oC. The time that
      it takes for the skin temperature on the fingers to reach 15oC will be recorded. With the
      finger skin temperature stable at 15oC, Finometer and laser Doppler measurements will be
      repeated and the 'core' temperature at this point noted. Then, the hand will be removed from
      the chamber, and allowed to equilibrate in room temperature. The time taken for the skin
      temperature to reach stability will be recorded, as will the absolute temperature that it
      stabilises to. Measures above will be repeated once hand temperature is stable. Once these
      measures have been made, all equipment will be removed and a 15ml blood sample will be taken
      (for epicatechin, glucose and insulin analysis). The participant will be asked to complete 3
      questionnaires (SF-36, Raynaud's symptoms and a food frequency questionnaire). Participants
      will also return a 4-day diet diary at visits 1 and 4, and their symptom diary at visit 4.

      Visits 2 (end of month 1) and 3 (end of month 2); participants will return a 4-day diet
      diary, symptom diary and any unused capsules. They will also have a resting blood pressure
      measurement made, weight measured and be asked to complete 3 questionnaires (SF-36, Raynaud's
      symptoms and a food frequency questionnaire).

      At the end of Visits 1, 2 and 3, participants will be given a months' supply of capsules, a
      symptom diary and a diet diary (to be completed in the week prior to the next visit).
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Double-blinded, placebo controlled study. Block randomised with equal allocation of participants between groups.
primary purpose: Prevention
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
masking description: Opaque capsules of equal size and appearance presented in similar bottles labelled only by a code. Code to product information is held by the manufacturer and un-blinding of the PI will only occur once the study analysis has been completed or in the event of a serious adverse event occurring.
measure: Vasospasm
time frame: 3 months
description: frequency of vasospasm
measure: Severity of vasospasm symptoms
time frame: 3 months
description: visual analogue score for pain associated with each vasospasm occasion. Participants indicate pain intensity by placing a vertical line on a 100mm horizontal line where the start of the line (left-hand side; 0mm) represents 'no pain' and the end of the line (right-hand side; 100mm) represents 'most severe pain'. Distance of the vertical line from 0 provides the visual analogue score. A lower score indicates a more favourable outcome.
measure: Duration of vasospasm symptoms
time frame: 3 months
description: duration that symptoms persist for on each vasospasm occasion
measure: Raynaud's Condition score
time frame: 3 months
description: Assessment of Raynaud's symptoms using the validated Raynaud's Condition Score. This is a 1 to 10 Likert scale, with 0 representing 'no difficulty' and 10 indicating 'extreme difficulty' with symptoms; collected daily for 3 months, a lower score indicates a more favourable outcome.
measure: Blood pressure
time frame: pre-intervention
description: blood pressure measured by automated oscillometric blood pressure
measure: Blood pressure
time frame: 4 weeks after starting intervention
description: blood pressure measured by automated oscillometric blood pressure
measure: Blood pressure
time frame: 8 weeks after starting intervention
description: blood pressure measured by automated oscillometric blood pressure
measure: Blood pressure
time frame: 12 weeks after starting the intervention
description: blood pressure measured by automated oscillometric blood pressure
measure: Dietary polyphenol intake
time frame: pre-intervention
description: estimation of dietary polyphenols made by food frequency questionnaire
measure: Dietary polyphenol intake
time frame: 4 weeks after starting intervention
description: estimation of dietary polyphenols made by food frequency questionnaire
measure: Dietary polyphenol intake
time frame: 8 weeks after starting intervention
description: estimation of dietary polyphenols made by food frequency questionnaire
measure: Dietary polyphenol intake
time frame: 12 weeks after starting the intervention
description: estimation of dietary polyphenols made by food frequency questionnaire
measure: Ambient skin temperature
time frame: pre-intervention
description: skin temperature of a finger exposed to an environmental temperature of 25oC, before cooling
measure: Ambient skin temperature
time frame: 12 weeks after starting the intervention
description: skin temperature of a finger exposed to an environmental temperature of 25oC, before cooling
measure: Ambient skin blood flow
time frame: pre-intervention
description: finger blood flow (measured using laser Doppler flowmetry) when exposed to an environmental temperature of 25oC, before cooling
measure: Ambient skin blood flow
time frame: 12 weeks after starting the intervention
description: finger blood flow (measured using laser Doppler flowmetry) when exposed to an environmental temperature of 25oC, before cooling
measure: Skin temperature response to acute cooling
time frame: pre-intervention
description: The time taken for skin temperature of the finger to stabilise in response to localised cooling (in an air temperature of 0oC)
measure: Skin temperature response to acute cooling
time frame: 12 weeks after starting the intervention
description: The time taken for skin temperature of the finger to stabilise in response to localised cooling (in an air temperature of 0oC)
measure: Skin blood flow response to acute cooling
time frame: pre-intervention
description: Finger Skin blood flow; measurement (using laser Doppler flowmetry) made once finger skin temperature has stabilised in response to localised cooling (in an air temperature of 0oC)
measure: Skin blood flow response to acute cooling
time frame: 12 weeks after starting the intervention
description: Finger Skin blood flow; measurement (using laser Doppler flowmetry) made once finger skin temperature has stabilised in response to localised cooling (in an air temperature of 0oC)
measure: Skin temperature response to re-warming
time frame: pre-intervention
description: The time taken for skin temperature of finger to stabilise in an environmental temperature of 25oC following localised cooling (in an air temperature of 0oC)
measure: Skin temperature response to re-warming
time frame: 12 weeks after starting the intervention
description: The time taken for skin temperature of finger to stabilise in an environmental temperature of 25oC following localised cooling (in an air temperature of 0oC)
measure: Skin temperature after re-warming
time frame: pre-intervention
description: skin temperature that a finger exposed to an environmental temperature of 25oC stabilises to after localised cooling
measure: Skin temperature after re-warming
time frame: 12 weeks after starting the intervention
description: skin temperature that a finger exposed to an environmental temperature of 25oC stabilises to after localised cooling
measure: Quality of life score
time frame: pre-intervention
description: Assessed using SF-36 questionnaire. Responses are coded and normalised to the UK population, as per standard methods, and a score for mental and physical health calculated; a higher score indicating a more favourable outcome
measure: Quality of life score
time frame: 4 weeks after starting intervention
description: Assessed using SF-36 questionnaire. Responses are coded and normalised to the UK population, as per standard methods, and a score for mental and physical health calculated; a higher score indicating a more favourable outcome
measure: Quality of life score
time frame: 8 weeks after starting intervention
description: Assessed using SF-36 questionnaire. Responses are coded and normalised to the UK population, as per standard methods, and a score for mental and physical health calculated; a higher score indicating a more favourable outcome
measure: Quality of life score
time frame: 12 weeks after starting the intervention
description: Assessed using SF-36 questionnaire. Responses are coded and normalised to the UK population, as per standard methods, and a score for mental and physical health calculated; a higher score indicating a more favourable outcome
measure: Attrition rate
time frame: 2 years
description: Number of participants completing the protocol as a proportion of those who were randomised to the study
measure: Adverse events
time frame: 3 months
description: Any injury, accident or illness experienced over the intervention period will be documented
measure: Recruitment rate
time frame: 2 years
description: number of people volunteering to take part in the study as a proportion of those expressing initial interest
arm group label: High Flavanol Cocoa extract
arm group type: Experimental
description: 278mg total flavanols (38.3mg epicatechin) per opaque cellulose capsule 3 capsules consumed once per day (836 mg total flavanols; 115mg epicatechin) for 3 months
arm group label: Alkalised cocoa
arm group type: Placebo Comparator
description: 0mg total flavanols (0mg epicatechin) per opaque cellulose capsule 3 capsules consumed once per day (0mg total flavanols; 0mg epicatechin) for 3 months
intervention type: Dietary Supplement
intervention name: High Flavanol Cocoa extract
description: Experimental group
arm group label: High Flavanol Cocoa extract
intervention type: Dietary Supplement
intervention name: Alkalised cocoa
description: Control group
arm group label: Alkalised cocoa
criteria: 
gender: All
minimum age: 18 Years
maximum age: 60 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Ian A Macdonald, PhD
role: Study Director
affiliation: University of Nottingham
facility: 
country: United Kingdom
citation: Herrick A. Raynaud's phenomenon. Curr Treat Options Cardiovasc Med. 2008 Apr;10(2):146-55. doi: 10.1007/s11936-008-0016-y.
PMID: 18325317
citation: Chung L, Shapiro L, Fiorentino D, Baron M, Shanahan J, Sule S, Hsu V, Rothfield N, Steen V, Martin RW, Smith E, Mayes M, Simms R, Pope J, Kahaleh B, Csuka ME, Gruber B, Collier D, Sweiss N, Gilbert A, Dechow FJ, Gregory J, Wigley FM. MQX-503, a novel formulation of nitroglycerin, improves the severity of Raynaud's phenomenon: a randomized, controlled trial. Arthritis Rheum. 2009 Mar;60(3):870-7. doi: 10.1002/art.24351.
PMID: 19248104
responsible party type: Principal Investigator
investigator affiliation: University of Nottingham
investigator full name: Elizabeth Simpson
investigator title: Senior Research Fellow
mesh term: Raynaud Disease
sharing ipd: No
ipd description: Individual data will not be shared with other researchers