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

Study Overview
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Brief Summary
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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.

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

Conditions
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Microangiopathy, Diabetic, Polyphenol, Optical Tomography, Vascular Endothelium, Arterial Stiffness, Healthy Participants

Intervention / Treatment
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* Dietary Supplement: Cocoa flavanol
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: 2 group (healthy and type 2 diabetes) randomised controlled cross-over (2-period, 2-sequence) study
Masking: Triple


Arms and Interventions

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

What is the study measuring?
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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 |