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

Diabetes Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01654172
• Other study ID #: 05/Q2401/146
• Status: Completed
• Phase: N/A
• First received: July 25, 2012
• Last updated: July 30, 2012
• Start date: September 2006
• Est. completion date: December 2008

Study information

• Verified date: July 2012
• Source: University of Nottingham
• Contact: n/a
• Is FDA regulated: No
• Health authority: United Kingdom: Research Ethics Committee
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 18
• Est. completion date: December 2008
• Est. primary completion date: December 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 35 Years to 70 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Basic Science

Related Conditions & MeSH terms

• Diabetes

Intervention

Dietary Supplement:
• High Flavanol Cocoa
Total daily flavanol intake provided by the high flavanol drink is ~900mg
• Low Flavanol Cocoa

Locations

Country	Name	City	State
United Kingdom	University of Nottingham	Nottingham	Notts

Sponsors (2)

Lead Sponsor	Collaborator
University of Nottingham	Mars, Inc.

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in Fasting Brain Blood Flow	Measured by ASL-MR at Day 0 and after 7d consumption of a cocoa drink to detect a change following intervention	Day 0 and after 7d consumption of a cocoa drink	No
Secondary	Change in Brain blood flow after acute consumption of cocoa	Measured at day 0, (before intervention commences)and after 7days consumption of a cocoa drink	1,3,5 and 8hrs after cocoa consumption	No
Secondary	Change in Fasting foot blood flow	Measured using ASL-MR	Day 0 and after 7d consumption of a cocoa drink	No
Secondary	Change in Foot blood flow after acute consumption of cocoa	Measured at day 0, (before intervention commences)and after 7days consumption of a cocoa drink	1,3,5 and 8hrs after cocoa consumption	No
Secondary	Change in Blood Flavanol concentration	Measured at day 0, (before intervention commences)and after 7days consumption of a cocoa drink	Day 0 and after 7d consumption of a cocoa drink	No
Secondary	Change in Fasting oxidative stress status	Oxidative stress assessed by measuring concentration of homocysteine, CRP, 8-isoprostaglandin, arginine and nitric oxide metabolites in the blood.	Day 0 and after 7 days of consuming a cocoa drink	No
Secondary	Change in diabetes control	Assessment made from HbA1c, glucose and insulin concentration in the blood	Day 0 and after 7days of consuming a cocoa drink daily	No