Controlled Clinical Trial to Determine the Effective Dose of Cocoa in Lowering Blood Pressure

Study Overview
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Brief Summary
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In Colombia, ischemic heart disease and stroke are one of the most important causes of death in 45 years old people. Care of cases of disease represents high costs for the health system in particular and society in general, due to the loss of productive years life and costs for the care of the aftermath. Hypertension (HT) is one of the preventable risk factors for major cerebrovascular disorders. The pathophysiology of Essential hypertension is complex and depends of interaction of genetic and environmental factors. Among the determining elements are the increase in the activity of the sympathetic nervous system, the vasoconstricting and overproduction of hormones associated with sodium retention, disruption in renin secretion with increased production of aldosterone and angiotensin II, the deregulation of the kinins system, the increase in peripheral vascular resistance and activity of Growth factors in atherogenesis and vascular endothelial dysfunction, increased cardiac output, diabetes mellitus, obesity, and lower production of vasodilators such as brain natriuretic peptide (BNP), the prostacyclins and nitric oxide (NO), among others. Cocoa is a food rich in flavonoids, which stimulate the enzyme activity of endothelial nitric oxide synthase (e-NOS), responsible of the production of NO in vascular smooth muscle. The flavonoids modulate the synthesis of inflammatory substances that are derived from endothelial cells and the immune system. In a recent study found that with a few grams of cocoa achieves a significant reduction in blood pressure, so the investigators propose a controlled clinical trial to assess the effect of different doses of cocoa on blood pressure and endothelial inflammation in men with essential hypertension, stage I-II without target organ damage, in addition to pharmacologic monotherapy defined for the management of their disease. The investigators hope to determine an optimal dose of cocoa, with long-term effects, by their high content of flavonoids, improves cardiovascular and endothelial parameters with the advantage that it is an economical and easy introduction into the patient's habits.

Official Title
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Controlled Clinical Trial of the Effect of Cocoa Consumption in Lowering Blood Pressure and in the Modulation of Endothelial Inflammation in Hypertensive Patients Assigned to an Entity Health Promoting.

Conditions
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Hypertension

Intervention / Treatment
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* Dietary Supplement: Delivery and return of chocolate
* Procedure: Determination of blood pressure
* Procedure: Anthropometric Measurements
* Procedure: Food Anamnesis
* Procedure: Samples: serological tests and culture of mononuclear cells
* Procedure: Analysis of cytokine production


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male Age: 18 - 65 years old Resides in Medellín City Attached from the contributive regimen of Colombian Health System Essential Arterial Hypertension, stage I or II. Be receiving pharmacologic therapy (maximum 2 medications), whose dose has been stable for eight weeks prior to study entry. Voluntary desire to consume 6,5; 12; 25 or 50 grams of chocolate per day for 18 weeks. Voluntary desire to participate in the trial and sign informed consent. Exclusion Criteria: Secondary hypertension Injury in target organ: heart, kidney, brain and retina Presence of diabetes mellitus BMI (Body Mass Index) major or equal to 30 Present smoker or with less than four weeks of abstinence of tobacco Consume antiplatelet substances Regular consumption of antioxidants and multivitamins During the study excluded any participant to present a sudden increase in blood pressure: SBP greater than or equal to 180 mmHg and/or DBP greater or equal to 110 mm Hg.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br> | Dietary Supplement: Delivery and return of chocolate<br>* At baseline and then every 2 weeks, each participant will receive different grams of chocolate, according to the group to which he is assigned.<br>Procedure: Determination of blood pressure<br>* Blood pressure will be determined at study entry, ninth and eighteenth week taking into account the protocols established in 2007 by the European Society of Cardiology and Hypertension. Because blood pressure has variations throughout the day and that measuring ambulatory health institutions can generate emotional changes that induce changes in this clinical setting, which for purposes of this study is the main outcome variable, there will be 24-hour monitoring of blood pressure at the beginning and end of the study.<br>Procedure: Anthropometric Measurements<br>* The study will be determined the body mass index (BMI) by the ratio of weight in kilograms over height in meters squared, for which anthropometric measurement will be made at first, ninth and the eighteenth week as follows: The weight will be taken with an electronic balance of 0.05 g sensitivity standing capacity of 150 kg. We will be rated based on BMI cut points given by WHO-PAHO (1993) and adopted by the Ministry of Health of Colombia (2000).<br>Procedure: Food Anamnesis<br>* With the aim of learning about the eating habits, it will be made based on a food intake recall the last 24 hours, taking into account that is not preceded by a special food day (sundays, holidays, celebrations). For more accurately calculate nutrient ingested food, modules will be used.<br>Procedure: Samples: serological tests and culture of mononuclear cells<br>* At admission and at the end of the study will be obtained after 12 hours of fasting, 8 mL of blood in a dry tube without anticoagulant and 30 mL of blood in heparin tubes, properly labeled with the code assigned to the participant. The sample will be used to determine the complete lipid profile (triglycerides, total cholesterol, LDL cholesterol, HDL cholesterol and VLDL cholesterol), State of oxidation of low density lipoprotein (oxLDL) and mononuclear cell culture. The remaining serum was kept at -20°C for use if is required repeat any study.<br>Procedure: Analysis of cytokine production<br>* We will be used the supernatant of mononuclears cell culture to quantify the production of interleukin one beta, interleukin two, tumor necrosis factor alpha by ELISA with commercially available kits for this purpose.<br>|
| Active Comparator: 6,5g Dose Group<br> | Dietary Supplement: Delivery and return of chocolate<br>* At baseline and then every 2 weeks, each participant will receive different grams of chocolate, according to the group to which he is assigned.<br>Procedure: Determination of blood pressure<br>* Blood pressure will be determined at study entry, ninth and eighteenth week taking into account the protocols established in 2007 by the European Society of Cardiology and Hypertension. Because blood pressure has variations throughout the day and that measuring ambulatory health institutions can generate emotional changes that induce changes in this clinical setting, which for purposes of this study is the main outcome variable, there will be 24-hour monitoring of blood pressure at the beginning and end of the study.<br>Procedure: Anthropometric Measurements<br>* The study will be determined the body mass index (BMI) by the ratio of weight in kilograms over height in meters squared, for which anthropometric measurement will be made at first, ninth and the eighteenth week as follows: The weight will be taken with an electronic balance of 0.05 g sensitivity standing capacity of 150 kg. We will be rated based on BMI cut points given by WHO-PAHO (1993) and adopted by the Ministry of Health of Colombia (2000).<br>Procedure: Food Anamnesis<br>* With the aim of learning about the eating habits, it will be made based on a food intake recall the last 24 hours, taking into account that is not preceded by a special food day (sundays, holidays, celebrations). For more accurately calculate nutrient ingested food, modules will be used.<br>Procedure: Samples: serological tests and culture of mononuclear cells<br>* At admission and at the end of the study will be obtained after 12 hours of fasting, 8 mL of blood in a dry tube without anticoagulant and 30 mL of blood in heparin tubes, properly labeled with the code assigned to the participant. The sample will be used to determine the complete lipid profile (triglycerides, total cholesterol, LDL cholesterol, HDL cholesterol and VLDL cholesterol), State of oxidation of low density lipoprotein (oxLDL) and mononuclear cell culture. The remaining serum was kept at -20°C for use if is required repeat any study.<br>Procedure: Analysis of cytokine production<br>* We will be used the supernatant of mononuclears cell culture to quantify the production of interleukin one beta, interleukin two, tumor necrosis factor alpha by ELISA with commercially available kits for this purpose.<br>|
| Active Comparator: 12g Dose Group<br> | Dietary Supplement: Delivery and return of chocolate<br>* At baseline and then every 2 weeks, each participant will receive different grams of chocolate, according to the group to which he is assigned.<br>Procedure: Determination of blood pressure<br>* Blood pressure will be determined at study entry, ninth and eighteenth week taking into account the protocols established in 2007 by the European Society of Cardiology and Hypertension. Because blood pressure has variations throughout the day and that measuring ambulatory health institutions can generate emotional changes that induce changes in this clinical setting, which for purposes of this study is the main outcome variable, there will be 24-hour monitoring of blood pressure at the beginning and end of the study.<br>Procedure: Anthropometric Measurements<br>* The study will be determined the body mass index (BMI) by the ratio of weight in kilograms over height in meters squared, for which anthropometric measurement will be made at first, ninth and the eighteenth week as follows: The weight will be taken with an electronic balance of 0.05 g sensitivity standing capacity of 150 kg. We will be rated based on BMI cut points given by WHO-PAHO (1993) and adopted by the Ministry of Health of Colombia (2000).<br>Procedure: Food Anamnesis<br>* With the aim of learning about the eating habits, it will be made based on a food intake recall the last 24 hours, taking into account that is not preceded by a special food day (sundays, holidays, celebrations). For more accurately calculate nutrient ingested food, modules will be used.<br>Procedure: Samples: serological tests and culture of mononuclear cells<br>* At admission and at the end of the study will be obtained after 12 hours of fasting, 8 mL of blood in a dry tube without anticoagulant and 30 mL of blood in heparin tubes, properly labeled with the code assigned to the participant. The sample will be used to determine the complete lipid profile (triglycerides, total cholesterol, LDL cholesterol, HDL cholesterol and VLDL cholesterol), State of oxidation of low density lipoprotein (oxLDL) and mononuclear cell culture. The remaining serum was kept at -20°C for use if is required repeat any study.<br>Procedure: Analysis of cytokine production<br>* We will be used the supernatant of mononuclears cell culture to quantify the production of interleukin one beta, interleukin two, tumor necrosis factor alpha by ELISA with commercially available kits for this purpose.<br>|
| Active Comparator: 25g Dose Group<br> | Dietary Supplement: Delivery and return of chocolate<br>* At baseline and then every 2 weeks, each participant will receive different grams of chocolate, according to the group to which he is assigned.<br>Procedure: Determination of blood pressure<br>* Blood pressure will be determined at study entry, ninth and eighteenth week taking into account the protocols established in 2007 by the European Society of Cardiology and Hypertension. Because blood pressure has variations throughout the day and that measuring ambulatory health institutions can generate emotional changes that induce changes in this clinical setting, which for purposes of this study is the main outcome variable, there will be 24-hour monitoring of blood pressure at the beginning and end of the study.<br>Procedure: Anthropometric Measurements<br>* The study will be determined the body mass index (BMI) by the ratio of weight in kilograms over height in meters squared, for which anthropometric measurement will be made at first, ninth and the eighteenth week as follows: The weight will be taken with an electronic balance of 0.05 g sensitivity standing capacity of 150 kg. We will be rated based on BMI cut points given by WHO-PAHO (1993) and adopted by the Ministry of Health of Colombia (2000).<br>Procedure: Food Anamnesis<br>* With the aim of learning about the eating habits, it will be made based on a food intake recall the last 24 hours, taking into account that is not preceded by a special food day (sundays, holidays, celebrations). For more accurately calculate nutrient ingested food, modules will be used.<br>Procedure: Samples: serological tests and culture of mononuclear cells<br>* At admission and at the end of the study will be obtained after 12 hours of fasting, 8 mL of blood in a dry tube without anticoagulant and 30 mL of blood in heparin tubes, properly labeled with the code assigned to the participant. The sample will be used to determine the complete lipid profile (triglycerides, total cholesterol, LDL cholesterol, HDL cholesterol and VLDL cholesterol), State of oxidation of low density lipoprotein (oxLDL) and mononuclear cell culture. The remaining serum was kept at -20°C for use if is required repeat any study.<br>Procedure: Analysis of cytokine production<br>* We will be used the supernatant of mononuclears cell culture to quantify the production of interleukin one beta, interleukin two, tumor necrosis factor alpha by ELISA with commercially available kits for this purpose.<br>|
| Active Comparator: 50g Dose Group<br> | Dietary Supplement: Delivery and return of chocolate<br>* At baseline and then every 2 weeks, each participant will receive different grams of chocolate, according to the group to which he is assigned.<br>Procedure: Determination of blood pressure<br>* Blood pressure will be determined at study entry, ninth and eighteenth week taking into account the protocols established in 2007 by the European Society of Cardiology and Hypertension. Because blood pressure has variations throughout the day and that measuring ambulatory health institutions can generate emotional changes that induce changes in this clinical setting, which for purposes of this study is the main outcome variable, there will be 24-hour monitoring of blood pressure at the beginning and end of the study.<br>Procedure: Anthropometric Measurements<br>* The study will be determined the body mass index (BMI) by the ratio of weight in kilograms over height in meters squared, for which anthropometric measurement will be made at first, ninth and the eighteenth week as follows: The weight will be taken with an electronic balance of 0.05 g sensitivity standing capacity of 150 kg. We will be rated based on BMI cut points given by WHO-PAHO (1993) and adopted by the Ministry of Health of Colombia (2000).<br>Procedure: Food Anamnesis<br>* With the aim of learning about the eating habits, it will be made based on a food intake recall the last 24 hours, taking into account that is not preceded by a special food day (sundays, holidays, celebrations). For more accurately calculate nutrient ingested food, modules will be used.<br>Procedure: Samples: serological tests and culture of mononuclear cells<br>* At admission and at the end of the study will be obtained after 12 hours of fasting, 8 mL of blood in a dry tube without anticoagulant and 30 mL of blood in heparin tubes, properly labeled with the code assigned to the participant. The sample will be used to determine the complete lipid profile (triglycerides, total cholesterol, LDL cholesterol, HDL cholesterol and VLDL cholesterol), State of oxidation of low density lipoprotein (oxLDL) and mononuclear cell culture. The remaining serum was kept at -20°C for use if is required repeat any study.<br>Procedure: Analysis of cytokine production<br>* We will be used the supernatant of mononuclears cell culture to quantify the production of interleukin one beta, interleukin two, tumor necrosis factor alpha by ELISA with commercially available kits for this purpose.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change on blood pressure in patients with stage I-II hypertension, after consumption of different doses of cocoa. |  | 18 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in the oxidation of low density lipoproteins after cocoa consumption, in patients with stage I-II hypertension. |  | 18 weeks | 
| Change in the production of inflammatory molecules derived from peripheral blood mononuclear cells of patients with arterial hypertension stage I-II, after cocoa consumption. |  | 18 weeks | 
| Change in platelet aggregation after cocoa consumption, in patients with essential arterial hypertension stage I-II. |  | 18 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cocoa, Chocolate, Endothelial disfunction, Cardiovascular disease, Blood Pressure, Hypertension