Macro- and Microvascular Response to Cocoa Flavanols in Healthy and Type 2 Diabetes

Proof-of-concept Study to Investigate Hand and Foot Microvascular Response to Cocoa Flavanols in Healthy and Type 2 Diabetes Participant

The greatest challenge in our ageing society are cardiovascular diseases such as stroke, heart attack, peripheral artery disease of the legs with non-healing wounds (ulcers), or diabetes. Specific diets with high polyphenol content are associated with lower incidence of cardiovascular disease and can improve macrovascular function when consumed acutely and chronically. Which role the smallest blood vessels (microcirculation) play in this and if the microcirculation responds to therapies is not well understood. One reason for this is that no generally available medical instrument has the resolution to study the microcirculation. The recently developed optical coherence tomography angiography (OCTA), currently mainly used by eye doctors, is able to visualise the microcirculation.

The current randomised controlled cross-over proof-of-concept study will test the acute effect of a cocoa flavanol intervention on cutaneous microvascular structure and function of hands and feet together with macrovascular function of upper and lower extremities in healthy and type 2 diabetes participants. It is the hypothesis that cocoa flavanol intervention as compared to placebo can acutely increase microvascular vasodilation and macrovascular endothelial function in arms and legs together with arterial stiffness in both healthy and type 2 diabetes participants.

Study Overview

• Status: Completed
• Conditions: Healthy Participants; Arterial Stiffness; Vascular Endothelium; Microangiopathy, Diabetic; Polyphenol; Optical Tomography
• Intervention / Treatment: Dietary supplement: Cocoa flavanol; Other: Placebo

• Study Type: Interventional
• Enrollment (Actual): 22
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United Kingdom
  • Guildford, United Kingdom, GU2 7XH
    • University of Surrey

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Healthy:

Inclusion Criteria:

• Healthy, 20-70 years
• BMI 20-30 kg/m^2

Exclusion Criteria:

• Diabetes mellitus
• Symptoms of acute infection
• Cardiac rhythm other than sinus
• Active malignancy
• Clinical signs or symptoms of cardiovascular disease (coronary artery disease, lower extremity artery disease, cerebrovascular disease): angina pectoris, dyspnea, palpitation, syncope, claudication
• Active vasoactive medication.

Type 2 Diabetes:

Inclusion Criteria:

• Type 2 diabetes mellitus
• 20-70 years
• BMI 20-30 kg/m^2

Exclusion Criteria:

• Symptoms of acute infection
• Cardiac rhythm other than sinus
• Active malignancy
• Clinical signs or symptoms of cardiovascular disease (coronary artery disease, lower extremity artery disease, cerebrovascular disease): angina pectoris, dyspnea, palpitation, syncope, claudication
• Active vasoactive medication.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Triple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Healthy participants: Cocoa flavanol - Placebo; Healthy participants receiving cocoa flavanols on first study day and placebo on second study day	Dietary supplement: Cocoa flavanol; Commercially available Cocoa Via Brand capsules containing 1350 mg cocoa flavanols (6 capsules); Other: Placebo; Capsules identical to ccocoa flavanol capsules filled with calorically matched brown sugar (6 capsules)
Other: Healthy participant: Placebo - Cocoa flavanol; Healthy participants receiving placebo on first study day and cocoa flavanols on second study day	Dietary supplement: Cocoa flavanol; Commercially available Cocoa Via Brand capsules containing 1350 mg cocoa flavanols (6 capsules); Other: Placebo; Capsules identical to ccocoa flavanol capsules filled with calorically matched brown sugar (6 capsules)
Other: Type 2 diabetes participants: Cocoa flavanol - Placebo; Participants with type 2 diabetes receiving cocoa flavanols on first study day and placebo on second study day	Dietary supplement: Cocoa flavanol; Commercially available Cocoa Via Brand capsules containing 1350 mg cocoa flavanols (6 capsules); Other: Placebo; Capsules identical to ccocoa flavanol capsules filled with calorically matched brown sugar (6 capsules)
Other: Type 2 diabetes participants: Placebo - Cocoa flavanol; Participants with type 2 diabetes receiving placebo on first study day and cocoa flavanols on second study day	Dietary supplement: Cocoa flavanol; Commercially available Cocoa Via Brand capsules containing 1350 mg cocoa flavanols (6 capsules); Other: Placebo; Capsules identical to ccocoa flavanol capsules filled with calorically matched brown sugar (6 capsules)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Microvascular dilation	Microvascular diameter increase in response to 5 min limb occlusion on hands and feet	Change at 2 hours as compared to baseline after ingestion of cocoa flavanol vs placebo
Macrovascular endothelial function	Flow-mediated dilation determined with ultrasound in brachial and common femoral artery	Change at 2 hours as compared to baseline after ingestion of cocoa flavanol vs placebo

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Arterial stiffness	Pulse wave velocity (Arteriograph)	Change at 2 hours as compared to baseline after ingestion of cocoa flavanol vs placebo
Blood pressure	Upper arm blood pressure measured with Arteriograph	Change at 2 hours as compared to baseline after ingestion of cocoa flavanol vs placebo
Leg perfusion pressure	Doppler based perfusion pressure of leg	Change at 2 hours as compared to baseline after ingestion of cocoa flavanol vs placebo

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Photoplethysmography (PPG) based pulse wave velocity (PWV)	PWV velocity calculated based on PPG sensor at hand and foot	Change at 2 hours as compared to baseline after ingestion of cocoa flavanol vs placebo
Photoplethysmography (PPG) blood flow	Based on PPG signals on hand and foot	Change at 2 hours as compared to baseline after ingestion of cocoa flavanol vs placebo

Collaborators and Investigators

• Sponsor: University of Surrey
• Investigators: Principal Investigator: Christian Heiss, Prof., University of Surrey, Department of Clinical and Experimental Medicine

Study record dates

Study Major Dates

• Study Start (Actual): May 17, 2021
• Primary Completion (Actual): June 1, 2021
• Study Completion (Actual): May 17, 2022

Study Registration Dates

• First Submitted: May 18, 2021
• First Submitted That Met QC Criteria: July 4, 2022
• First Posted (Actual): July 8, 2022

Study Record Updates

• Last Update Posted (Actual): July 8, 2022
• Last Update Submitted That Met QC Criteria: July 4, 2022
• Last Verified: May 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Endocrine System Diseases; Diabetes Complications; Diabetes Mellitus; Diabetic Angiopathies
• Other Study ID Numbers: OCTA2

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No
• IPD Plan Description: Will be decided on an individual basis and after study completion.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No