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

This study has been completed.
Sponsor:
Collaborator:
Mars, Inc.
Information provided by (Responsible Party):
University of Nottingham
ClinicalTrials.gov Identifier:
NCT01654172
First received: July 25, 2012
Last updated: July 30, 2012
Last verified: July 2012
  Purpose

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.


Condition Intervention
Diabetes
Dietary Supplement: High Flavanol Cocoa
Dietary Supplement: Low Flavanol Cocoa

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Basic Science
Official Title: Effect of Flavanol-rich Cocoa on Peripheral and Cerebral Blood Flow in Type 2 Diabetes

Resource links provided by NLM:


Further study details as provided by University of Nottingham:

Primary Outcome Measures:
  • Change in Fasting Brain Blood Flow [ Time Frame: Day 0 and after 7d consumption of a cocoa drink ] [ Designated as safety issue: No ]
    Measured by ASL-MR at Day 0 and after 7d consumption of a cocoa drink to detect a change following intervention


Secondary Outcome Measures:
  • Change in Brain blood flow after acute consumption of cocoa [ Time Frame: 1,3,5 and 8hrs after cocoa consumption ] [ Designated as safety issue: No ]
    Measured at day 0, (before intervention commences)and after 7days consumption of a cocoa drink

  • Change in Fasting foot blood flow [ Time Frame: Day 0 and after 7d consumption of a cocoa drink ] [ Designated as safety issue: No ]
    Measured using ASL-MR

  • Change in Foot blood flow after acute consumption of cocoa [ Time Frame: 1,3,5 and 8hrs after cocoa consumption ] [ Designated as safety issue: No ]
    Measured at day 0, (before intervention commences)and after 7days consumption of a cocoa drink

  • Change in Blood Flavanol concentration [ Time Frame: Day 0 and after 7d consumption of a cocoa drink ] [ Designated as safety issue: No ]
    Measured at day 0, (before intervention commences)and after 7days consumption of a cocoa drink

  • Change in Fasting oxidative stress status [ Time Frame: Day 0 and after 7 days of consuming a cocoa drink ] [ Designated as safety issue: No ]
    Oxidative stress assessed by measuring concentration of homocysteine, CRP, 8-isoprostaglandin, arginine and nitric oxide metabolites in the blood.

  • Change in diabetes control [ Time Frame: Day 0 and after 7days of consuming a cocoa drink daily ] [ Designated as safety issue: No ]
    Assessment made from HbA1c, glucose and insulin concentration in the blood


Enrollment: 18
Study Start Date: September 2006
Study Completion Date: December 2008
Primary Completion Date: December 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: High Flavanol Cocoa

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

Subject consumes 2 servings per day, for 7 days.

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

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

Subject consumes 2 servings per day, for 7 days.

Dietary Supplement: Low Flavanol Cocoa

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.

  Eligibility

Ages Eligible for Study:   35 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01654172

Locations
United Kingdom
University of Nottingham
Nottingham, Notts, United Kingdom, NG72UH
Sponsors and Collaborators
University of Nottingham
Mars, Inc.
Investigators
Principal Investigator: Simon Paige, MD University Hospitals NHS Trust
  More Information

No publications provided

Responsible Party: University of Nottingham
ClinicalTrials.gov Identifier: NCT01654172     History of Changes
Other Study ID Numbers: 05/Q2401/146
Study First Received: July 25, 2012
Last Updated: July 30, 2012
Health Authority: United Kingdom: Research Ethics Committee

Keywords provided by University of Nottingham:
Diabetes
peripheral neuropathy
Cocoa flavanols

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases

ClinicalTrials.gov processed this record on July 23, 2014