Acute Hemodynamic Effects of Cocoa Polyphenols in Subjects With Hypertension and Optimal Blood Pressure

Randomized Controlled, Double-Blind, Sample Size-Calculated, Three-Period Crossover, Phase 1 Study to Investigate the Efficacy of a Single Oral Dose of Cocoa Phenols on Blood, Pressure, Heart Rate and Plasma Levels of Phenols, Bioactive Nitric Oxide and Oxidation Markers in Subjects With Stage 1 Essential Hypertension and Optimal Blood Pressure

Sponsors

Lead Sponsor: University of Cologne

Source University of Cologne
Brief Summary

Intake of cocoa-containing foods has been found to lower blood pressure (BP) in several clinical trials. It is supposed that the cocoa polyphenols represent the active principle, lowering BP by increasing the formation of vasodilative nitric oxide. However, direct evidence for this assumption from controlled clinical studies is lacking. Moreover, in hypertensive subjects vascular dilation appears to be impaired due to endothelial dysfunction and vascular smooth muscle remodeling, but it is unclear whether the BP response to cocoa phenols differs between subjects with high blood pressure and optimal blood pressure.

The investigators hypothesized that (1) intake of cocoa phenols cause a dose-dependent, acute elevation of circulating bioactive NO levels and a reduction in BP, and that (2) the NO elevation and BP reduction are impaired in patients with hypertension.

To test this hypothesis, the investigators will conduct a prospective, randomized, placebo-controlled, double-blind, sample size-calculated, three-period crossover study with pre-planned statistical analysis and trial monitoring, in which cocoa phenols will be orally administered to subjects with mild essential hypertension or subjects with optimal blood pressure. The effects on blood pressure, heart rate, arterial function and plasma levels of cocoa phenols, circulating bioactive nitric oxide, and plasma markers of oxidative stress will be evaluated. After a 7-day cocoa-free run-in period and a 12-hour overnight fast, 48 subjects (24 with hypertension and 24 sex-, and age (+/- 2yrs)-matched subjects with optimal blood pressure) will receive either a single dose of 1000 mg cocoa polyphenols, 250 mg cocoa phenols or placebo (in capsules of equal form and weight). Each intervention will be followed by a 7-day cocoa-free washout period before cross-over to the subsequent intervention. Subjects will be allocated to the intervention sequence by permuted block randomization (i.e. permuted blocks of 2 subjects with high BP and 2 subjects with optimal BP each, are assigned to permutations of the tree interventions). Measurements of hemodynamic and plasma parameters will be performed directly before and 30, 60, 90, 120, 180, 300, and 480 min after capsule administration. Included subjects will be counseled to maintain their usual diet and physical activity and to abstain from all cocoa products during the study. Analysis of the data will be performed on an intention-to-treat basis.

Overall Status Completed
Start Date October 2007
Primary Completion Date September 2008
Phase Phase 1
Study Type Interventional
Primary Outcome
Measure Time Frame
Change in systolic and diastolic blood pressure Assessments at 3 time points
Secondary Outcome
Measure Time Frame
Changes in plasma levels of bioactive nitric oxide, arterial function, oxidation markers and cocoa polyphenols Assessments at 3 time points
Enrollment 48
Condition
Intervention

Intervention Type: Dietary Supplement

Intervention Name: cocoa polyphenols

Description: Oral administration of capsules with 1000 mg polyphenols, 250 mg polyphenols or placebo

Arm Group Label: 1

Intervention Type: Dietary Supplement

Intervention Name: cocoa polyphenols

Description: Oral administration of capsules with 1000 mg polyphenols, 250 mg polyphenols or placebo

Arm Group Label: 2

Eligibility

Criteria:

Inclusion Criteria:

- Unpaid volunteers of both sex between 50 and 75 years of age in good general health.

- Diagnosis of stage 1 essential hypertension (BP between 140/90 and 160/100 mmHg) or optimal BP below 120/80) and stable BP values.

- No antihypertensive medications or nutritional supplements.

- Non-manual workers or pensioners of higher socioeconomic status (household income of more than 20,000 €/year)

- Leisure physical activity of less than 7 METs per week

- Normal levels of plasma lipids and plasma glucose.

Exclusion Criteria:

- Cardiovascular diseases (other than hypertension).

- Diabetes mellitus.

- Hyper-/dyslipidemia.

- Gastrointestinal diseases

- Hepatic and renal disorders

- Pulmonary diseases.

- Coagulopathy.

- Cancer.

- Psychiatric disorders.

- Alcohol or drug dependence.

- Seizure disorders.

- History of organ transplantation.

- Surgery within the last 12 months.

- Positive tests for HIV, hepatitis B or C.

- Body-mass index of more than 27.5 or less than 18.5 kg/m2

- Active smokers of tobacco within the last five years.

- Regular users of medications.

- Use of any medication within the last two weeks before entry.

- Users of vitamin, mineral or polyphenol supplements or other bioactive food supplements.

- Regular consumers of chocolate or other cocoa products of more than 1 serving per week.

- Subjects will be excluded if they are unable to give informed consent for all procedures. Subjects who are not capable or willing to attend to all interventions will be withdrawn.

- Subjects will be withdrawn if the allocation concealment is disclosed.

- Subjects will be withdrawn if any adverse events requiring further monitoring or medical treatment occur.

- A systolic BP >170 mmHg or <100 mmHg or a diastolic BP >110 mmHg or <50 mmHg at a single determination will result in immediate withdrawal of the participant from the study and the appropriate treatment will be resumed.

Gender: All

Minimum Age: 50 Years

Maximum Age: 75 Years

Healthy Volunteers: Accepts Healthy Volunteers

Overall Official
Last Name Role Affiliation
Dirk Taubert, MD, PhD Principal Investigator University of Cologne
Location
Facility: Department of Pharmacology, University of Cologne
Location Countries

Germany

Verification Date

February 2009

Responsible Party

Name Title: Dirk Taubert

Organization: University of Cologne

Has Expanded Access No
Condition Browse
Number Of Arms 2
Arm Group

Label: 1

Type: Experimental

Description: Subjects with stage 1 hypertension

Label: 2

Type: Experimental

Description: Subjects with optimal blood pressure

Study Design Info

Allocation: Randomized

Intervention Model: Crossover Assignment

Primary Purpose: Treatment

Masking: Triple (Participant, Investigator, Outcomes Assessor)

Source: ClinicalTrials.gov