NCT01276951

Brief Summary

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
125

participants targeted

Target at P50-P75 for not_applicable hypertension

Timeline
Completed

Started Dec 2008

Typical duration for not_applicable hypertension

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

December 1, 2008

Completed
1.5 years until next milestone

First Submitted

Initial submission to the registry

May 24, 2010

Completed
8 months until next milestone

First Posted

Study publicly available on registry

January 14, 2011

Completed
8 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

September 1, 2011

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

September 1, 2011

Completed
Last Updated

January 24, 2017

Status Verified

January 1, 2017

Enrollment Period

2.8 years

First QC Date

May 24, 2010

Last Update Submit

January 23, 2017

Conditions

Hypertension

Keywords

CocoaChocolateEndothelial disfunctionCardiovascular diseaseBlood PressureHypertension

Outcome Measures

Primary Outcomes (1)

  • Change on blood pressure in patients with stage I-II hypertension, after consumption of different doses of cocoa.

    18 weeks

Secondary Outcomes (3)

  • 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

Study Arms (5)

Placebo

PLACEBO COMPARATOR
Dietary Supplement: Delivery and return of chocolateProcedure: Determination of blood pressureProcedure: Anthropometric MeasurementsProcedure: Food AnamnesisProcedure: Samples: serological tests and culture of mononuclear cellsProcedure: Analysis of cytokine production

6,5g Dose Group

ACTIVE COMPARATOR
Dietary Supplement: Delivery and return of chocolateProcedure: Determination of blood pressureProcedure: Anthropometric MeasurementsProcedure: Food AnamnesisProcedure: Samples: serological tests and culture of mononuclear cellsProcedure: Analysis of cytokine production

12g Dose Group

ACTIVE COMPARATOR
Dietary Supplement: Delivery and return of chocolateProcedure: Determination of blood pressureProcedure: Anthropometric MeasurementsProcedure: Food AnamnesisProcedure: Samples: serological tests and culture of mononuclear cellsProcedure: Analysis of cytokine production

25g Dose Group

ACTIVE COMPARATOR
Dietary Supplement: Delivery and return of chocolateProcedure: Determination of blood pressureProcedure: Anthropometric MeasurementsProcedure: Food AnamnesisProcedure: Samples: serological tests and culture of mononuclear cellsProcedure: Analysis of cytokine production

50g Dose Group

ACTIVE COMPARATOR
Dietary Supplement: Delivery and return of chocolateProcedure: Determination of blood pressureProcedure: Anthropometric MeasurementsProcedure: Food AnamnesisProcedure: Samples: serological tests and culture of mononuclear cellsProcedure: Analysis of cytokine production

Interventions

Delivery and return of chocolateDIETARY_SUPPLEMENT

At baseline and then every 2 weeks, each participant will receive different grams of chocolate, according to the group to which he is assigned.

12g Dose Group25g Dose Group50g Dose Group6,5g Dose GroupPlacebo
Determination of blood pressurePROCEDURE

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.

12g Dose Group25g Dose Group50g Dose Group6,5g Dose GroupPlacebo
Anthropometric MeasurementsPROCEDURE

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).

12g Dose Group25g Dose Group50g Dose Group6,5g Dose GroupPlacebo
Food AnamnesisPROCEDURE

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.

12g Dose Group25g Dose Group50g Dose Group6,5g Dose GroupPlacebo
Samples: serological tests and culture of mononuclear cellsPROCEDURE

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.

12g Dose Group25g Dose Group50g Dose Group6,5g Dose GroupPlacebo
Analysis of cytokine productionPROCEDURE

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.

12g Dose Group25g Dose Group50g Dose Group6,5g Dose GroupPlacebo

Eligibility Criteria

Age18 Years - 65 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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.

You may not qualify if:

  • 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Sede Investigaciones Universitarias, Universidad de Antioquia

Medellín, Antioquia, 05001000, Colombia

Location

Related Publications (25)

  • 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. doi: 10.1161/01.HYP.0000174990.46027.70. Epub 2005 Jul 18.

    PMID: 16027246BACKGROUND

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

    PMID: 15902773BACKGROUND

  • Oparil S, Zaman MA, Calhoun DA. Pathogenesis of hypertension. Ann Intern Med. 2003 Nov 4;139(9):761-76. doi: 10.7326/0003-4819-139-9-200311040-00011. No abstract available.

    PMID: 14597461BACKGROUND

  • Cifkova R. The burden of hypertension and inadequate control in populations. J Hypertens. 2006 May;24(5):807-9. doi: 10.1097/01.hjh.0000222745.52325.e7. No abstract available.

    PMID: 16612237BACKGROUND

  • 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. doi: 10.1161/01.HYP.0000107251.49515.c2. Epub 2003 Dec 1.

    PMID: 14656957BACKGROUND

  • 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. doi: 10.1097/00004872-200401000-00003.

    PMID: 15106785BACKGROUND

  • Aristizabal D GE, McEwen J, Caulfiel M, Mendez J, Medina E, Zapata N, Correa M. Bases genéticas de la hipertension arterial esencial en Colombia: avances en nueve años de estudio. Revista Colombiana de Cardiología. 12(6), 2006.

    BACKGROUND

  • Beevers G, Lip GY, O'Brien E. ABC of hypertension: The pathophysiology of hypertension. BMJ. 2001 Apr 14;322(7291):912-6. doi: 10.1136/bmj.322.7291.912. No abstract available.

    PMID: 11302910BACKGROUND

  • 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. doi: 10.1097/HJH.0b013e3281fc975a. No abstract available.

    PMID: 17563527BACKGROUND

  • Steinberg D. Atherogenesis in perspective: hypercholesterolemia and inflammation as partners in crime. Nat Med. 2002 Nov;8(11):1211-7. doi: 10.1038/nm1102-1211. No abstract available.

    PMID: 12411947BACKGROUND

  • 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. doi: 10.1001/jama.289.19.2560. Epub 2003 May 14.

    PMID: 12748199BACKGROUND

  • Taubert D, Roesen R, Schomig E. Effect of cocoa and tea intake on blood pressure: a meta-analysis. Arch Intern Med. 2007 Apr 9;167(7):626-34. doi: 10.1001/archinte.167.7.626.

    PMID: 17420419BACKGROUND

  • 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. doi: 10.1073/pnas.0510168103. Epub 2006 Jan 17.

    PMID: 16418281BACKGROUND

  • 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. doi: 10.1097/00005344-200606001-00003.

    PMID: 16794446BACKGROUND

  • Fisher ND, Sorond FA, Hollenberg NK. Cocoa flavanols and brain perfusion. J Cardiovasc Pharmacol. 2006;47 Suppl 2:S210-4. doi: 10.1097/00005344-200606001-00017.

    PMID: 16794460BACKGROUND

  • 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.

    PMID: 1729957BACKGROUND

  • 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. doi: 10.1042/CS20060048.

    PMID: 16551272BACKGROUND

  • 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. doi: 10.1001/jama.298.1.49.

    PMID: 17609490BACKGROUND

  • 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. doi: 10.1001/jama.290.8.1029. No abstract available.

    PMID: 12941673BACKGROUND

  • 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. doi: 10.1093/ajcn/81.3.611.

    PMID: 15755830BACKGROUND

  • 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. doi: 10.1001/jama.290.8.1030. No abstract available.

    PMID: 12941674BACKGROUND

  • Mursu J, Voutilainen S, Nurmi T, Rissanen TH, Virtanen JK, Kaikkonen J, Nyyssonen 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. doi: 10.1016/j.freeradbiomed.2004.06.002.

    PMID: 15454274BACKGROUND

  • 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. doi: 10.1038/nm1102-1218. No abstract available.

    PMID: 12411948BACKGROUND

  • 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. doi: 10.1097/00005344-200606001-00010.

    PMID: 16794453BACKGROUND

  • 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. doi: 10.1093/ajcn/81.1.298S.

    PMID: 15640494BACKGROUND

MeSH Terms

Conditions

HypertensionCardiovascular Diseases

Interventions

Parturition

Condition Hierarchy (Ancestors)

Vascular Diseases

Intervention Hierarchy (Ancestors)

PregnancyReproductionReproductive Physiological PhenomenaReproductive and Urinary Physiological Phenomena

Study Officials

  • Mónica L. Giraldo Restrepo, Nurse. PhD

    Universidad de Antioquia

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
not applicable
Allocation
RANDOMIZED
Masking
TRIPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

May 24, 2010

First Posted

January 14, 2011

Study Start

December 1, 2008

Primary Completion

September 1, 2011

Study Completion

September 1, 2011

Last Updated

January 24, 2017

Record last verified: 2017-01

Data Sharing

IPD Sharing
Will not share

Locations

CO(1)