Effect of Flavanol-rich Cocoa on Peripheral and Cerebral Blood Flow in Type 2 Diabetes

NCT ID: NCT01654172

Last Updated: 2012-07-31

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 18 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2006-09-30
• Study Completion Date: 2008-12-31

Brief Summary

Cocoa flavanols form part of the family of chemicals (also found in red wine and tea) which have aroused interest due to population studies suggesting that diets high in these substances might reduce risks of heart disease. In the laboratory, these flavanols have been shown to cause blood vessels to widen and blood flow to increase. As dysfunction in this ability of blood vessels to widen is now thought to play a central role in the complications of diabetes, novel ways to mitigate this are constantly being sought.

The present study aims to use non-invasive magnetic resonance imaging (MRI) to measure foot and brain blood flow before and after 7 days consumption of a cocoa drink high in flavanols, in subjects with diabetes, with and without peripheral neuropathy.

Detailed Description

Cocoa flavanols form part of the family of polyphenols (also found in red wine and tea) which have aroused interest due to epidemiological studies suggesting that diets high in these substances might reduce risks of heart disease. However, it is difficult to account for all sources of polyphenols in these epidemiological studies, and the level of cocoa product consumption was generally not well documented. Furthermore, in readily available cocoa products, processing may remove most of the flavanols, leading to such products varying considerably in flavanol content. Recently, laboratory studies of the effects of cocoa flavanols have suggested an effect on the relaxation of smooth muscle in blood vessel walls, specifically the element mediated by the endothelium (blood vessel wall). Studies using ultrasound methods in healthy volunteers have shown an increase in blood flow in the arm following temporary arterial occlusion.

As endothelial dysfunction is now thought to play a central role in the complications of diabetes, novel ways to mitigate this are constantly being sought. It is well recognised that diabetic peripheral nerve damage leads to abnormal foot blood flow, including impaired superficial skin blood flow, and that this is one of the factors delaying wound healing in diabetic foot ulcers (the single largest cost in secondary care diabetes).

Several techniques are currently used to monitor blood flow to the limbs, including venous occlusion plethysmography (VOP), laser Doppler methods and nuclear medicine techniques. These techniques have low spatial resolution, low specificity, are labour intensive, or require the use of injected radioactive contrast agents (which pose a particular risk to diabetic patients). Radiation dose also limits repeat studies.

The arterial spin labelling magnetic resonance (ASL MR) technique is non-invasive, but yields a quantifiable measure of blood flow with high resolution, and allows measurements to be repeated several times, as the technique uses no external contrast agents.

The present study aims to use non-invasive magnetic resonance imaging (MRI) to measure peripheral (foot) and brain blood flow at baseline and in response to a cocoa drink high in flavanols, in subjects with type 2 diabetes, with and without peripheral neuropathy.

Subjects will attend an initial screening visit. Measures of HbA1c, kidney function and blood pressure will be checked, along with ankle-brachial pressure index (to check for poor circulation), foot pulses, and examination for peripheral nerve damage and cardiac neuropathy.

Conditions

Diabetes

Keywords

Diabetes; peripheral neuropathy; Cocoa flavanols

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: QUADRUPLE

Study Groups

High Flavanol Cocoa

Cocoa drink containing ~450mg cocoa flavanols and 10g carbohydrate per serving.

Subject consumes 2 servings per day, for 7 days.

Group Type: EXPERIMENTAL

High Flavanol Cocoa

Intervention Type: DIETARY_SUPPLEMENT

Total daily flavanol intake provided by the high flavanol drink is \~900mg

Low Flavanol Cocoa

Cocoa drink containing ~25mg cocoa flavanols and 10g carbohydrate per serving.

Subject consumes 2 servings per day, for 7 days.

Group Type: PLACEBO_COMPARATOR

Low Flavanol Cocoa

Intervention Type: DIETARY_SUPPLEMENT

Interventions

High Flavanol Cocoa

Total daily flavanol intake provided by the high flavanol drink is \~900mg

Intervention Type: DIETARY_SUPPLEMENT

Low Flavanol Cocoa

Intervention Type: DIETARY_SUPPLEMENT

Eligibility Criteria

Inclusion Criteria

• Type 2 diabetes
• Peripheral neuropathy or free from neuropathy

Exclusion Criteria

• Current foot ulceration
• Hypertension
• Anti-hypertensive medications other than thiazide diuretics and ACE inhibitors
• Ischaemic heart disease
• Peripheral vascular disease (ABPI ,0.9 &/or impalpable foot pulses)
• Chronic kidney disease
• Poor glycaemic control
• DVT
• Epilepsy
• Pregnancy
• Contraindications to MRI
• Intolerance to lactose or cow's milk protein

• Minimum Eligible Age: 35 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Mars, Inc.

INDUSTRY

Sponsor Role: collaborator

University of Nottingham

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Simon Paige, MD

Role: PRINCIPAL_INVESTIGATOR

University Hospitals NHS Trust

Locations

University of Nottingham

Nottingham, Notts, United Kingdom

Countries

United Kingdom

Other Identifiers

05/Q2401/146

Identifier Type: -

Identifier Source: org_study_id