Cocoa Flavanol Supplementation in Raynaud's Phenomenon
Condition: Primary Raynaud Phenomenon
MeSH terms: Raynaud Disease
Study type: Interventional

Summary: 
      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.
    

Detailed description: 
      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).
    

Intervention name(s): High Flavanol Cocoa extract; Alkalised cocoa
Intervention type(s): Dietary Supplement; Dietary Supplement
Intervention description(s): Experimental group; Control group
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Double-blinded, placebo controlled study. Block randomised with equal allocation of participants between groups.
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Prevention
Keywords: cocoa flavanols