Controlled Clinical Trial to Determine the Effective Dose of Cocoa in Lowering Blood Pressure - Full Text View

Purpose

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.

Condition	Intervention
Hypertension	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

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator) Primary Purpose: Treatment
Official Title:	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.

Resource links provided by NLM:

MedlinePlus related topics: High Blood Pressure

U.S. FDA Resources

Further study details as provided by Universidad de Antioquia:

Primary Outcome Measures:

Change on blood pressure in patients with stage I-II hypertension, after consumption of different doses of cocoa. [ Time Frame: 18 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Change in the oxidation of low density lipoproteins after cocoa consumption, in patients with stage I-II hypertension. [ Time Frame: 18 weeks ] [ Designated as safety issue: No ]
Change in the production of inflammatory molecules derived from peripheral blood mononuclear cells of patients with arterial hypertension stage I-II, after cocoa consumption. [ Time Frame: 18 weeks ] [ Designated as safety issue: No ]
Change in platelet aggregation after cocoa consumption, in patients with essential arterial hypertension stage I-II. [ Time Frame: 18 weeks ] [ Designated as safety issue: No ]

Estimated Enrollment:	125
Study Start Date:	December 2008
Estimated Study Completion Date:	March 2011
Estimated Primary Completion Date:	December 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Placebo Comparator: Placebo	Dietary Supplement: Delivery and return of chocolate At baseline and then every 2 weeks, each participant will receive different grams of chocolate, according to the group to which he is assigned. Procedure: Determination of blood pressure 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. Procedure: Anthropometric Measurements 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). Procedure: Food Anamnesis 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. Procedure: Samples: serological tests and culture of mononuclear cells 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. Procedure: Analysis of cytokine production 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.
Active Comparator: 6,5g Dose Group	Dietary Supplement: Delivery and return of chocolate At baseline and then every 2 weeks, each participant will receive different grams of chocolate, according to the group to which he is assigned. Procedure: Determination of blood pressure 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. Procedure: Anthropometric Measurements 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). Procedure: Food Anamnesis 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. Procedure: Samples: serological tests and culture of mononuclear cells 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. Procedure: Analysis of cytokine production 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.
Active Comparator: 12g Dose Group	Dietary Supplement: Delivery and return of chocolate At baseline and then every 2 weeks, each participant will receive different grams of chocolate, according to the group to which he is assigned. Procedure: Determination of blood pressure 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. Procedure: Anthropometric Measurements 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). Procedure: Food Anamnesis 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. Procedure: Samples: serological tests and culture of mononuclear cells 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. Procedure: Analysis of cytokine production 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.
Active Comparator: 25g Dose Group	Dietary Supplement: Delivery and return of chocolate At baseline and then every 2 weeks, each participant will receive different grams of chocolate, according to the group to which he is assigned. Procedure: Determination of blood pressure 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. Procedure: Anthropometric Measurements 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). Procedure: Food Anamnesis 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. Procedure: Samples: serological tests and culture of mononuclear cells 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. Procedure: Analysis of cytokine production 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.
Active Comparator: 50g Dose Group	Dietary Supplement: Delivery and return of chocolate At baseline and then every 2 weeks, each participant will receive different grams of chocolate, according to the group to which he is assigned. Procedure: Determination of blood pressure 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. Procedure: Anthropometric Measurements 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). Procedure: Food Anamnesis 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. Procedure: Samples: serological tests and culture of mononuclear cells 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. Procedure: Analysis of cytokine production 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.

Eligibility

Ages Eligible for Study:	18 Years to 65 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01276951

Contacts

Contact: Mónica L. Giraldo Restrepo, Nurse. PhD

(574) 2106474

mlgiraldo@une.net.co

Locations

Colombia
Sede Investigaciones Universitarias, Universidad de Antioquia	Recruiting
Medellín, Antioquia, Colombia, 05001000
Contact: Mónica Lucía Giraldo Restrepo, Nurse. PhD Inmunology (574) 2106474 mlgiraldo@une.net.co
Principal Investigator: Mónica Lucía Giraldo Restrepo, Nurse. PhD Inmunology
Sub-Investigator: Héctor Iván García García, MD. Epidemiologist
Sub-Investigator: Gloria Margarita Alcaraz López, Nutritionist
Sub-Investigator: Juan Manuel Toro Escobar, Internal Medicine
Sub-Investigator: José Robinson Ramírez Pineda, Geneticist
Sub-Investigator: Pablo Javier Grajales, MD.PhD Inmunology
Sub-Investigator: Carlos J. Jaramillo Gómez, Cardiologist
Sub-Investigator: Gabriel Bedoya Berrío

Sponsors and Collaborators

Universidad de Antioquia

Instituto Colombiano para el Desarrollo de la Ciencia y la Tecnología (COLCIENCIAS)

Investigators

Principal Investigator:

Mónica L. Giraldo Restrepo, Nurse. PhD

Universidad de Antioquia

More Information

Publications:

Grassi D, Necozione S, Lippi C, Croce G, Valeri L, Pasqualetti P, Desideri G, Blumberg JB, Ferri C. Cocoa reduces blood pressure and insulin resistance and improves endothelium-dependent vasodilation in hypertensives. Hypertension. 2005 Aug;46(2):398-405. Epub 2005 Jul 18.

[No authors listed] WHO publishes definitive atlas on global heart disease and stroke epidemic. Indian J Med Sci. 2004 Sep;58(9):405-6. No abstract available.

Oparil S, Zaman MA, Calhoun DA. Pathogenesis of hypertension. Ann Intern Med. 2003 Nov 4;139(9):761-76. Review. No abstract available.

Cífková R. The burden of hypertension and inadequate control in populations. J Hypertens. 2006 May;24(5):807-9. No abstract available.

Chobanian AV, Bakris GL, Black HR, Cushman WC, Green LA, Izzo JL Jr, Jones DW, Materson BJ, Oparil S, Wright JT Jr, Roccella EJ; Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. National Heart, Lung, and Blood Institute; National High Blood Pressure Education Program Coordinating Committee. Seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. Hypertension. 2003 Dec;42(6):1206-52. Epub 2003 Dec 1.

Kearney PM, Whelton M, Reynolds K, Whelton PK, He J. Worldwide prevalence of hypertension: a systematic review. J Hypertens. 2004 Jan;22(1):11-9. Review.

Beevers G, Lip GY, O'Brien E. ABC of hypertension: The pathophysiology of hypertension. BMJ. 2001 Apr 14;322(7291):912-6. Review. No abstract available.

Mancia G, De Backer G, Dominiczak A, Cifkova R, Fagard R, Germano G, Grassi G, Heagerty AM, Kjeldsen SE, Laurent S, Narkiewicz K, Ruilope L, Rynkiewicz A, Schmieder RE, Boudier HA, Zanchetti A, Vahanian A, Camm J, De Caterina R, Dean V, Dickstein K, Filippatos G, Funck-Brentano C, Hellemans I, Kristensen SD, McGregor K, Sechtem U, Silber S, Tendera M, Widimsky P, Zamorano JL, Erdine S, Kiowski W, Agabiti-Rosei E, Ambrosioni E, Lindholm LH, Viigimaa M, Adamopoulos S, Agabiti-Rosei E, Ambrosioni E, Bertomeu V, Clement D, Erdine S, Farsang C, Gaita D, Lip G, Mallion JM, Manolis AJ, Nilsson PM, O'Brien E, Ponikowski P, Redon J, Ruschitzka F, Tamargo J, van Zwieten P, Waeber B, Williams B; Management of Arterial Hypertension of the European Society of Hypertension; European Society of Cardiology. 2007 Guidelines for the Management of Arterial Hypertension: The Task Force for the Management of Arterial Hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC). J Hypertens. 2007 Jun;25(6):1105-87. No abstract available. Erratum in: J Hypertens. 2007 Aug;25(8):1749.

Steinberg D. Atherogenesis in perspective: hypercholesterolemia and inflammation as partners in crime. Nat Med. 2002 Nov;8(11):1211-7. No abstract available.

Chobanian AV, Bakris GL, Black HR, Cushman WC, Green LA, Izzo JL Jr, Jones DW, Materson BJ, Oparil S, Wright JT Jr, Roccella EJ; National Heart, Lung, and Blood Institute Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure; National High Blood Pressure Education Program Coordinating Committee. The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: the JNC 7 report. JAMA. 2003 May 21;289(19):2560-72. Epub 2003 May 14. Erratum in: JAMA. 2003 Jul 9;290(2):197.

Taubert D, Roesen R, Schömig E. Effect of cocoa and tea intake on blood pressure: a meta-analysis. Arch Intern Med. 2007 Apr 9;167(7):626-34.

Schroeter H, Heiss C, Balzer J, Kleinbongard P, Keen CL, Hollenberg NK, Sies H, Kwik-Uribe C, Schmitz HH, Kelm M. (-)-Epicatechin mediates beneficial effects of flavanol-rich cocoa on vascular function in humans. Proc Natl Acad Sci U S A. 2006 Jan 24;103(4):1024-9. Epub 2006 Jan 17.

McCullough ML, Chevaux K, Jackson L, Preston M, Martinez G, Schmitz HH, Coletti C, Campos H, Hollenberg NK. Hypertension, the Kuna, and the epidemiology of flavanols. J Cardiovasc Pharmacol. 2006;47 Suppl 2:S103-9; discussion 119-21.

Fisher ND, Sorond FA, Hollenberg NK. Cocoa flavanols and brain perfusion. J Cardiovasc Pharmacol. 2006;47 Suppl 2:S210-4.

Tsuruchi N, Jimi S. [A case of recurrent endometrial cancer successfully treated with oral administration of etoposide]. Gan To Kagaku Ryoho. 1992 Jan;19(1):103-5. Japanese.

Farouque HM, Leung M, Hope SA, Baldi M, Schechter C, Cameron JD, Meredith IT. Acute and chronic effects of flavanol-rich cocoa on vascular function in subjects with coronary artery disease: a randomized double-blind placebo-controlled study. Clin Sci (Lond). 2006 Jul;111(1):71-80.

Taubert D, Roesen R, Lehmann C, Jung N, Schomig E. Effects of low habitual cocoa intake on blood pressure and bioactive nitric oxide: a randomized controlled trial. JAMA. 2007 Jul 4;298(1):49-60.

Taubert D, Berkels R, Roesen R, Klaus W. Chocolate and blood pressure in elderly individuals with isolated systolic hypertension. JAMA. 2003 Aug 27;290(8):1029-30. No abstract available.

Grassi D, Lippi C, Necozione S, Desideri G, Ferri C. Short-term administration of dark chocolate is followed by a significant increase in insulin sensitivity and a decrease in blood pressure in healthy persons. Am J Clin Nutr. 2005 Mar;81(3):611-4.

Heiss C, Dejam A, Kleinbongard P, Schewe T, Sies H, Kelm M. Vascular effects of cocoa rich in flavan-3-ols. JAMA. 2003 Aug 27;290(8):1030-1. No abstract available.

Mursu J, Voutilainen S, Nurmi T, Rissanen TH, Virtanen JK, Kaikkonen J, Nyyssönen K, Salonen JT. Dark chocolate consumption increases HDL cholesterol concentration and chocolate fatty acids may inhibit lipid peroxidation in healthy humans. Free Radic Biol Med. 2004 Nov 1;37(9):1351-9.

Binder CJ, Chang MK, Shaw PX, Miller YI, Hartvigsen K, Dewan A, Witztum JL. Innate and acquired immunity in atherogenesis. Nat Med. 2002 Nov;8(11):1218-26. Review. No abstract available.

Selmi C, Mao TK, Keen CL, Schmitz HH, Eric Gershwin M. The anti-inflammatory properties of cocoa flavanols. J Cardiovasc Pharmacol. 2006;47 Suppl 2:S163-71; discussion S172-6. Review.

Keen CL, Holt RR, Oteiza PI, Fraga CG, Schmitz HH. Cocoa antioxidants and cardiovascular health. Am J Clin Nutr. 2005 Jan;81(1 Suppl):298S-303S. Review.

Responsible Party:	Mónica Lucía Giraldo Restrepo, Universidad de Antioquia
ClinicalTrials.gov Identifier:	NCT01276951 History of Changes
Other Study ID Numbers:	Cacao III
Study First Received:	May 24, 2010
Last Updated:	January 13, 2011
Health Authority:	National Institutes of Health: Colombia

Keywords provided by Universidad de Antioquia:

Cocoa
Chocolate
Endothelial disfunction

Cardiovascular disease
Blood Pressure
Hypertension

Additional relevant MeSH terms:

Hypertension
Vascular Diseases
Cardiovascular Diseases

ClinicalTrials.gov processed this record on June 18, 2013