Clinical trial NCT01671514: Effects of Dark Chocolate on Exercise Capacity, and Mitochondrial Structure and Function
Official title: Effects of Epicatechin-enriched Dark Chocolate on Mitochondrial Function and Exercise Capacity in Patients With Both Diabetes and Heart Failure and in Sedentary Individuals
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Heart Failure
Type 2 Diabetes
Keywords: mitochondrial biogenesis
skeletal muscle
epicatechin
Lead sponsor: University of California, San Diego
Sponsor class: OTHER
Collaborators: name: The Hershey Company
First posted: 2012-08-23
Enrollment: 21
Sex: ALL
Minimum age (years): 40
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL

Brief summary: The major goal of this study is to characterize the ability of dark chocolate enriched in epicatechin (a component of dark chocolate) to improve the structural and functional features of mitochondria in two groups

1. Patients with heart failure (HF) and type 2 diabetes (DM2) and
2. Normal yet sedentary individuals with impaired baseline exercise capacity (as assessed by VO2 max)

We propose that a 3 month treatment with dark chocolate will lead to a significant improvement in exercise capacity which will be secondary to the improvement in skeletal muscle structure from epicatechin.

Detailed description: The flavanol epicatechin (which is derived from cocoa and has no known toxicity in humans) has been shown in clinical trials to increase levels of nitric oxide (NO) as assessed by flow-mediated dilation (FMD) in the brachial artery and measurements of circulating NO in plasma. NO is thought to be an activator of PGC-1 alpha \[PPAR (peroxisome proliferator-activated receptor) alpha coactivator 1\] which stimulates mitochondrial biogenesis. In both patients with heart failure and diabetes there is nitric oxide deficiency and mitochondrial dysfunction. In our proposed double-blinded placebo controlled clinical trial, we will test the hypothesis that chronic administration of epicatechin to patients with both heart failure and diabetes will increase levels of NO and PGC-1 alpha leading to increased mitochondrial biogenesis and improved mitochondrial function. We believe similar changes will occur in sedentary individuals.

In a preliminary study with 5 patients with heart failure and diabetes (conducted under UCSD IRB protocol number #090688) we have shown that epicatechin enriched dark chocolate improves mitochondrial structure (Taub PR, Ramirez-Sanchez I, Ciaraldi TP, et al. Alterations in Skeletal Muscle Indicators of Mitochondrial Structure and Biogenesis in Patients with Type 2 Diabetes and Heart Failure: Effects of Epicatechin Rich Cocoa. Clin Transl Sci. 2011;5(1):43-47.)

Eligibility criteria: Healthy, sedentary individuals:

Inclusion Criteria:

* Healthy, inactive individuals
* BMI 27-32

Exclusion Criteria:

* Smoking or quit smoking less than 1 year prior to enrollment
* Currently taking Coumadin or Pradaxa.

Heart failure and diabetes patients:

Inclusion Criteria:

* Medically diagnosed with heart failure and diabetes
* No significant HbA1C fluctuations in past 6 months

Exclusion Criteria:

* Currently taking Insulin
* Currently taking Coumadin or Pradaxa.
* Smoking or quit smoking less than 1 year prior to enrollment

Primary outcomes:
measure: Change from baseline in exercise capacity
timeFrame: Baseline and 3 months
measure: Change from baseline in skeletal muscle metabolism
timeFrame: Baseline and 3 months
measure: Change from baseline in pre-specified biomarker levels in blood, skeletal muscle, and urine
timeFrame: Baseline and 3 months
Secondary outcomes:
Other outcomes:
measure: Change from baseline in quality of life, health, and nutrition questionnaires
timeFrame: Baseline and 3 months
Locations:
city: La Jolla
country: United States
facility: University of California, San Diego
state: California
Study officials:
affiliation: Assistant Professor of Medicine, University of California, San Diego
name: Pam Taub, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Taub PR, Ramirez-Sanchez I, Ciaraldi TP, Perkins G, Murphy AN, Naviaux R, Hogan M, Maisel AS, Henry RR, Ceballos G, Villarreal F. Alterations in skeletal muscle indicators of mitochondrial structure and biogenesis in patients with type 2 diabetes and heart failure: effects of epicatechin rich cocoa. Clin Transl Sci. 2012 Feb;5(1):43-7. doi: 10.1111/j.1752-8062.2011.00357.x. Epub 2011 Nov 7.