Cardiovascular DiseaseNCT01099150
Dark Chocolate and Platelet Function in Humans
A study testing Dark chocolate enriched in flavan-3-ols and procyanidins, Standard dark chocolate and White chocolate in people with Cardiovascular Disease, run by University of Aberdeen at 1 site in United Kingdom.
Trial summary
Cardiovascular disease is a major cause of mortality worldwide and responsible for one out of three global deaths. A main characteristic of cardiovascular disease is impaired blood flow and formation of blood clots. Platelets are clot-forming cells responsible for the prevention of bleeding. Read more about this study
- Who is it for?
- Ages 18 to 70 yearsHealthy volunteers can take part
- Conditions the study is for
- Cardiovascular Disease
- What is being tested?
- Dark chocolate enriched in flavan-3-ols and procyanidins, Standard dark chocolate and White chocolate
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 42 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- Mar 2009to May 2011
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Healthy male and/or female volunteers, aged between 18 and 70 years
Who cannot join
- Subjects are excluded if:
- they are taking aspirin or aspirin-containing drugs, other anti-inflammatory drugs, or any drugs or herbal medicines known to alter platelet function or the haemostatic system in general (without a minimum washout period of one month)
- they are taking fish oils or evening primrose oil, or fat soluble vitamin supplements within the last 4 weeks
- they are taking any medicine known to affect lipid and/or glucose metabolism
- they are taking hormone replacement therapy
- they have any known clinical signs of diabetes, hypertension, renal, hepatic, hematological disease, gastrointestinal disorders, endocrine disorders, coronary heart disease, infection or cancer
Show all 19Show fewer
- they are suffering from alcohol or any other substance abuse or are having eating disorders
- they are usually consuming a vegetarian diet
- they have a BMI below 18 or above 35 kg/ sqm
- they are undertaking more than 6 hours of vigorous exercise per week
- they are having an abnormal menstrual cycle
- they are pregnant
- they suffer from an allergy to cocoa or any of the ingredients contained within either of the chocolate bars
- they have been giving a pint of blood for transfusion purposes within the last month
- they have a low platelet count (< 170 x 10E09/ L)
- they have unsuitable veins for blood sampling and/ or cannulation
- their hematocrit is below 40 % for males and 35 % for females
- their haemoglobin is below 130 g/ L for males and 115 g/ L for females
- they are not able to travel on their own to the Rowett Institute of Nutrition and Health, Aberdeen for each of the interventions
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
University of Aberdeen Rowett Institute of Nutrition and Health
Aberdeen, Aberdeenshire, AB21 9SB
About this study
Official title: Acute Effects of the Consumption of Dark Chocolate Enriched in Flavan-3-ols on Platelet Function and the Platelet Proteome
Cardiovascular disease is a major cause of mortality worldwide and responsible for one out of three global deaths. A main characteristic of cardiovascular disease is impaired blood flow and formation of blood clots. Platelets are clot-forming cells responsible for the prevention of bleeding. However, in disease conditions they may be overly activated, promoting blood clots and blockage of blood vessels.
Consumption of diets rich in fruits and vegetables decreases mortality from cardiovascular disease through a number of mechanisms, including the prevention of platelet clotting and aggregation. There is some evidence suggesting that platelet aggregation may be modulated through a group of compounds known as flavan-3-ols, which are found in various foods, and especially in cocoa. However, the mechanisms by which those compounds affect platelet function are not yet fully understood. We designed a human study assessing the mechanisms by which flavan-3-ols from cocoa beneficially affect platelet function and the platelet proteome.
Read the detailed description
Cardiovascular disease (CVD) is a primary cause of premature deaths worldwide, with incidence rates in the United Kingdom, particularly in Scotland, being amongst the highest worldwide. Thus identification of dietary components that most effectively prevent CVD is potentially of wide public health benefit.
Consumption of diets rich in plant-based products protects against the development of CVD. Such effects have been ascribed in part to polyphenols, which are non-nutritive but, potentially bioactive secondary metabolites ubiquitous found in fruits, vegetables, herbs, spices, teas and wines. The beneficial effects of polyphenols on CVD is believed to be mediated, at least in part, though improving platelet function. At least 10 human intervention studies found a consistent and robust beneficial effect of cocoa products on platelet function, but unfortunately all of these studies used only one or two methods to assess platelet function, therefore only getting limited insights into the complex physiological behavior of platelets. In addition, none of these studies assessed potential mechanisms by which flavan-3-ols may inhibit platelet function. Schramm et al. have shown that consumption of chocolate rich in flavan-3-ols and their oligomers (procyanidins) lead to increased production of prostacyclin, a strong platelet inhibitor. This finding has also been observed when aortic endothelial cells are treated with procyanidins in vitro. Thus the stimulation of prostacyclin production in endothelial cells may reflect one pathway by which flavan-3-ols indirectly inhibit platelet activation. Many other potential mechanisms are discussed in the literature but so far the evidence for such mechanisms is limited or non-existing.
In this study we assess effects of consumption of chocolate enriched in flavan-3-ols on platelet function by measuring not only platelet aggregation, but also in vitro coagulation and platelet activation in healthy humans. In addition, we examine the effects of consumption of flavan-3-ols on the regulation of the platelet proteome to elucidate pathways by which these bioactive cocoa compounds affect platelet function.
HYPOTHESIS
Acute consumption of a moderate amount of dark chocolate enriched in flavan-3-ols results in decreased platelet activation and aggregation by decreasing the levels of thromboxane A2 produced by endothelial cells.
OBJECTIVES
The main objective of the proposed study is to determine whether consumption of 60 g dark chocolate enriched in flavan-3-ols results in decreased platelet activation and aggregation by decreasing levels of thromboxane A2, as well as assessing what other mechanisms could be involved.
The specific objectives of the proposed study are to determine:
- whether acute intake of 60 g dark chocolate enriched in flavan-3-ols, as compared with standard dark chocolate low in flavan-3-ols and white chocolate containing no flavan-3-ols, affects platelet aggregation, thromboxane A2 formation upon aggregation, in vitro bleeding time, P-selectin expression, and activation of the fibrinogen receptor;
- whether and how acute intake of 60 g dark chocolate enriched in flavan-3-ols, as compared with standard dark chocolate and white chocolate, affects the platelet proteome, and thereby potential new biomarkers of platelet function, as well as protein levels of anti-oxidant enzymes;
- identities and concentrations of flavan-3-ols and their metabolites in plasma and/ or urine 2 and 6 h after acute intake of 60 g dark chocolate enriched in flavan-3-ols, as compared with standard dark chocolate and white chocolate.
- Conditions
- Cardiovascular Disease
- Being tested
- Dark chocolate enriched in flavan-3-ols and procyanidins, Standard dark chocolate, White chocolate
- Keywords
- Platelets, Platelet aggregation, Platelet activation, Platelet function, Light transmission aggregometry, Platelet Function Analyzer-100 (PFA-100), P-selectin, Fibrinogen receptor, Glycoprotein IIb-IIIa, Chocolate, Cocoa, Flavan-3-ols, Procyanidins
- Medical subject headings
- Cardiovascular Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Dark chocolate enriched in flavan-3-ols and procyanidinsDietary supplement
Also called CocoanOX12%-containing chocolate
Acute consumption (within 15 minutes) of 60 g of chocolate containing ~900 mg of total flavan-3-ols and procyanidins.
Standard dark chocolateDietary supplement
Acute consumption (within 15 minutes) of 60 g of chocolate containing ~400 mg total flavan-3-ols and procyanidins.
White chocolateDietary supplement
Acute consumption (within 15 minutes) of 60 g of white chocolate containing no flavan-3-ols and procyanidins.
| Study group | Role | What they receive |
|---|---|---|
| 42 healthy volunteers - crossover | Experimental | Acute consumption of three interventions (60 g dark chocolate enriched in flavan-3-ols, 60 g standard dark chocolate, or 60 g white chocolate) on three separate days (at least 2 weeks apart) in random order.
Post-prandial measurements at t = 0 h, t = 2 h and t = 6 h. Receives: Dietary Supplement: Dark chocolate enriched in flavan-3-ols and procyanidins; Dietary Supplement: Standard dark chocolate; Dietary Supplement: White chocolate |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in light transmission aggregometry of platelet-rich plasma
- Using a Helena Platelet Aggregation Chromogenic Kinetics System-4 (PACKS-4) light transmission aggregometer
- Induced by adenosine diphosphate (ADP) and thrombin receptor-activating peptide (TRAP)
Measured: Post-prandial, up to 6 hours after chocolate consumption
Secondary outcomes (14)
Change in ex vivo bleeding time using the Platelet Function Analyzer-100 (PFA-100)
Using collagen-epinephrine coated cartridges.
Measured: Post-prandial, up to 6 hours after chocolate consumption
Change in P-selectin expression and activation of the fibrinogen receptor by flow cytometry
- P-selectin expression as early marker for platelet activation
- Activated fibrinogen receptor as late marker for platelet activation
- Induced by ADP and TRAP
- Using BD FACSArray Bioanalyzer
Measured: Post-prandial, up to 6 hours after chocolate consumption
Levels of flavan-3-ols and their metabolites in plasma and urine
- Using liquid chromatography-tandem mass spectrometry (LC-MS/MS)
- Enzyme-hydrolysed for total flavan-3-ols ((-)-epicatechin equivalents)
- Non-Hydrolysed for metabolic profile
Measured: Post-prandial, up to 6 hours after chocolate consumption
Changes in the platelet proteome
Using 2D-gel electrophoresis and LC-MS/MS identification of proteins.
Measured: Post-prandial, 2 hours after chocolate ingestion
Changes in thromboxane A2 production induced by ADP and TRAP
Using enzyme-linked immunosorbent assay (ELISA) in plasma after platelet aggregation
Measured: Post-prandial, up to 6 hours after chocolate consumption
Levels of prostacyclin and/ or leukotrienes in plasma
Using high performance liquid chromatography (HPLC) and/ or immunoassays
Measured: Post-prandial, up to 6 hours after chocolate consumption
Total phenolics in urine
Using the Folin-Ciocalteu assay
Measured: Post-prandial, up to 6 hours after chocolate consumption
Total catechins in urine
Using an adaption of the DMACA assay
Measured: Post-prandial, up to 6 hours after chocolate consumption
Urinary creatinine
Using a Thermo KONELAB 30 selective chemistry analyser (Thermo Scientific, Hertfordshire, UK) and its respective kit
To be used for normalisation of urinary flavan-3-ols and total phenolics from spot urine samples.
Measured: Post-prandial, up to 6 hours after chocolate consumption
Analysis of flavan-3-ol and procyanidin contents in study chocolates
Using an HPLC method
Measured: At the beginning (April 2009) and end (October 2009) of the intervention period
Non-targeted 1H-NMR of plasma and urine samples
To establish a metabolic profile - markers of intake and potential effects on host metabolism
Measured: Post-prandial, up to 6 hours after chocolate consumption
Non-targeted LC-MS of urine samples
To establish a metabolic profile - markers of intake and potential effects on host metabolism
Measured: Post-prandial, just before and 6 hours after chocolate consumption
Markers of oxidative stress in plasma
- Plasma levels of lipid peroxides (thiobarbituric acid-reactive substances, TBARS)
- Activity of glutathione peroxidase (Only at t = 2 h after chocolate ingestion)
Measured: Post-prandial, up to 6 hours after chocolate consumption
Fatty acid analysis of study chocolates
Using the fatty acid methyl ester (FAME) analysis and a gas chromatographic approach
Measured: Shortly after the intervention period was finished (February 2009)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Apr 2010 (estimated)
- Study startMar 2009
- Primary completionNov 2009
- Study completionMay 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (23)Papers the sponsor has linked to this study.
- Other trials for Cardiovascular DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Single blind
- Who is masked
- Investigator
- Enrolment
- 42 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Aberdeen
- Sponsor type
- University, hospital or other
- Collaborators
- Rural and Environment Research and Analysis Directorate (RERAD, UK), Biotechnology and Biological Sciences Research Council, Natraceutical Industrial S.L.U., Valencia, Spain
- Responsible party
- Sponsor
- Investigators
- Baukje de Roos, MSc PhD, Principal investigator, University of Aberdeen Rowett Institute of Nutrition and Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01099150
- Sponsor's protocol ID
- 600
- Other IDs
- 09/002
- Status last verified
- Apr 2012
- First submitted
- 25 Mar 2010
- Last updated
- 17 Apr 2012
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Baba S, Osakabe N, Yasuda A, Natsume M, Takizawa T, Nakamura T, Terao J. Bioavailability of (-)-epicatechin upon intake of chocolate and cocoa in human volunteers. Free Radic Res. 2000 Nov;33(5):635-41. doi: 10.1080/10715760000301151.
PubMed 11200094Bordeaux B, Yanek LR, Moy TF, White LW, Becker LC, Faraday N, Becker DM. Casual chocolate consumption and inhibition of platelet function. Prev Cardiol. 2007 Fall;10(4):175-80. doi: 10.1111/j.1520-037x.2007.06693.x.
PubMed 17917513de Roos B, Duthie SJ, Polley AC, Mulholland F, Bouwman FG, Heim C, Rucklidge GJ, Johnson IT, Mariman EC, Daniel H, Elliott RM. Proteomic methodological recommendations for studies involving human plasma, platelets, and peripheral blood mononuclear cells. J Proteome Res. 2008 Jun;7(6):2280-90. doi: 10.1021/pr700714x. Epub 2008 May 20.
PubMed 18489134Flammer AJ, Hermann F, Sudano I, Spieker L, Hermann M, Cooper KA, Serafini M, Luscher TF, Ruschitzka F, Noll G, Corti R. Dark chocolate improves coronary vasomotion and reduces platelet reactivity. Circulation. 2007 Nov 20;116(21):2376-82. doi: 10.1161/CIRCULATIONAHA.107.713867. Epub 2007 Nov 5.
PubMed 17984375Guerrero JA, Navarro-Nunez L, Lozano ML, Martinez C, Vicente V, Gibbins JM, Rivera J. Flavonoids inhibit the platelet TxA(2) signalling pathway and antagonize TxA(2) receptors (TP) in platelets and smooth muscle cells. Br J Clin Pharmacol. 2007 Aug;64(2):133-44. doi: 10.1111/j.1365-2125.2007.02881.x. Epub 2007 Apr 10.
PubMed 17425630Hamed MS, Gambert S, Bliden KP, Bailon O, Singla A, Antonino MJ, Hamed F, Tantry US, Gurbel PA. Dark chocolate effect on platelet activity, C-reactive protein and lipid profile: a pilot study. South Med J. 2008 Dec;101(12):1203-8. doi: 10.1097/SMJ.0b013e31818859eb.
PubMed 19005437Heptinstall S, May J, Fox S, Kwik-Uribe C, Zhao L. Cocoa flavanols and platelet and leukocyte function: recent in vitro and ex vivo studies in healthy adults. J Cardiovasc Pharmacol. 2006;47 Suppl 2:S197-205; discussion S206-9. doi: 10.1097/00005344-200606001-00015.
PubMed 16794458Hermann F, Spieker LE, Ruschitzka F, Sudano I, Hermann M, Binggeli C, Luscher TF, Riesen W, Noll G, Corti R. Dark chocolate improves endothelial and platelet function. Heart. 2006 Jan;92(1):119-20. doi: 10.1136/hrt.2005.063362. No abstract available.
PubMed 16365364Hubbard GP, Wolffram S, de Vos R, Bovy A, Gibbins JM, Lovegrove JA. Ingestion of onion soup high in quercetin inhibits platelet aggregation and essential components of the collagen-stimulated platelet activation pathway in man: a pilot study. Br J Nutr. 2006 Sep;96(3):482-8.
PubMed 16925853Hubbard GP, Wolffram S, Lovegrove JA, Gibbins JM. Ingestion of quercetin inhibits platelet aggregation and essential components of the collagen-stimulated platelet activation pathway in humans. J Thromb Haemost. 2004 Dec;2(12):2138-45. doi: 10.1111/j.1538-7836.2004.01067.x.
PubMed 15613018Innes AJ, Kennedy G, McLaren M, Bancroft AJ, Belch JJ. Dark chocolate inhibits platelet aggregation in healthy volunteers. Platelets. 2003 Aug;14(5):325-7. doi: 10.1080/0953710031000123681.
PubMed 12944249Mavrommatis Y, O'Kennedy N, de Roos B et al. Effect of eicosapentaenoic acid or docosahexaenoic acid intervention on platelet aggregation: does soluble epoxide hydrolase play a role? unpublished, 2010
Murphy KJ, Chronopoulos AK, Singh I, Francis MA, Moriarty H, Pike MJ, Turner AH, Mann NJ, Sinclair AJ. Dietary flavanols and procyanidin oligomers from cocoa (Theobroma cacao) inhibit platelet function. Am J Clin Nutr. 2003 Jun;77(6):1466-73. doi: 10.1093/ajcn/77.6.1466.
PubMed 12791625Nardini M, Natella F, Scaccini C. Role of dietary polyphenols in platelet aggregation. A review of the supplementation studies. Platelets. 2007 May;18(3):224-43. doi: 10.1080/09537100601078083.
PubMed 17497435Natella F, Nardini M, Belelli F, Pignatelli P, Di Santo S, Ghiselli A, Violi F, Scaccini C. Effect of coffee drinking on platelets: inhibition of aggregation and phenols incorporation. Br J Nutr. 2008 Dec;100(6):1276-82. doi: 10.1017/S0007114508981459. Epub 2008 Apr 28.
PubMed 18439332
Study at a glance
From the registry record, last updated by the sponsor on 17 Apr 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Acute Effects of the Consumption of Dark Chocolate Enriched in Flavan-3-ols on Platelet Function and the Platelet Proteome
- ClinicalTrials.gov ID
- NCT01099150
- Acronym / sponsor ID
- 600
- Conditions
- Cardiovascular Disease
- Keywords
- Platelets, Platelet aggregation, Platelet activation, Platelet function, Light transmission aggregometry, Platelet Function Analyzer-100 (PFA-100), P-selectin, Fibrinogen receptor
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 42 participants (actual)
- Lead sponsor
- University of AberdeenUniversity, hospital or other
- Collaborators
- Rural and Environment Research and Analysis Directorate (RERAD, UK), Biotechnology and Biological Sciences Research Council, Natraceutical Industrial S.L.U., Valencia, Spain
- Study start
- Mar 2009
- Primary completion
- Nov 2009 (actual)
- Study completion
- May 2011 (actual)
- First posted
- 6 Apr 2010 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Cardiovascular disease is a major cause of mortality worldwide and responsible for one out of three global deaths. A main characteristic of cardiovascular disease is impaired blood flow and formation of blood clots. Platelets are clot-forming cells responsible for the prevention of bleeding. However, in disease conditions they may be overly activated, promoting blood clots and blockage of blood vessels.
Consumption of diets rich in fruits and vegetables decreases mortality from cardiovascular disease through a number of mechanisms, including the prevention of platelet clotting and aggregation. There is some evidence suggesting that platelet aggregation may be modulated through a group of compounds known as flavan-3-ols, which are found in various foods, and especially in cocoa. However, the mechanisms by which those compounds affect platelet function are not yet fully understood. We designed a human study assessing the mechanisms by which flavan-3-ols from cocoa beneficially affect platelet function and the platelet proteome.
Detailed description
Cardiovascular disease (CVD) is a primary cause of premature deaths worldwide, with incidence rates in the United Kingdom, particularly in Scotland, being amongst the highest worldwide. Thus identification of dietary components that most effectively prevent CVD is potentially of wide public health benefit.
Consumption of diets rich in plant-based products protects against the development of CVD. Such effects have been ascribed in part to polyphenols, which are non-nutritive but, potentially bioactive secondary metabolites ubiquitous found in fruits, vegetables, herbs, spices, teas and wines. The beneficial effects of polyphenols on CVD is believed to be mediated, at least in part, though improving platelet function. At least 10 human intervention studies found a consistent and robust beneficial effect of cocoa products on platelet function, but unfortunately all of these studies used only one or two methods to assess platelet function, therefore only getting limited insights into the complex physiological behavior of platelets. In addition, none of these studies assessed potential mechanisms by which flavan-3-ols may inhibit platelet function. Schramm et al. have shown that consumption of chocolate rich in flavan-3-ols and their oligomers (procyanidins) lead to increased production of prostacyclin, a strong platelet inhibitor. This finding has also been observed when aortic endothelial cells are treated with procyanidins in vitro. Thus the stimulation of prostacyclin production in endothelial cells may reflect one pathway by which flavan-3-ols indirectly inhibit platelet activation. Many other potential mechanisms are discussed in the literature but so far the evidence for such mechanisms is limited or non-existing.
In this study we assess effects of consumption of chocolate enriched in flavan-3-ols on platelet function by measuring not only platelet aggregation, but also in vitro coagulation and platelet activation in healthy humans. In addition, we examine the effects of consumption of flavan-3-ols on the regulation of the platelet proteome to elucidate pathways by which these bioactive cocoa compounds affect platelet function.
HYPOTHESIS
Acute consumption of a moderate amount of dark chocolate enriched in flavan-3-ols results in decreased platelet activation and aggregation by decreasing the levels of thromboxane A2 produced by endothelial cells.
OBJECTIVES
The main objective of the proposed study is to determine whether consumption of 60 g dark chocolate enriched in flavan-3-ols results in decreased platelet activation and aggregation by decreasing levels of thromboxane A2, as well as assessing what other mechanisms could be involved.
The specific objectives of the proposed study are to determine:
- whether acute intake of 60 g dark chocolate enriched in flavan-3-ols, as compared with standard dark chocolate low in flavan-3-ols and white chocolate containing no flavan-3-ols, affects platelet aggregation, thromboxane A2 formation upon aggregation, in vitro bleeding time, P-selectin expression, and activation of the fibrinogen receptor;
- whether and how acute intake of 60 g dark chocolate enriched in flavan-3-ols, as compared with standard dark chocolate and white chocolate, affects the platelet proteome, and thereby potential new biomarkers of platelet function, as well as protein levels of anti-oxidant enzymes;
- identities and concentrations of flavan-3-ols and their metabolites in plasma and/ or urine 2 and 6 h after acute intake of 60 g dark chocolate enriched in flavan-3-ols, as compared with standard dark chocolate and white chocolate.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Single blind (investigator)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| 42 healthy volunteers - crossover | Experimental | Dietary Supplement: Dark chocolate enriched in flavan-3-ols and procyanidins, Dietary Supplement: Standard dark chocolate, Dietary Supplement: White chocolateAcute consumption of three interventions (60 g dark chocolate enriched in flavan-3-ols, 60 g standard dark chocolate, or 60 g white chocolate) on three separate days (at least 2 weeks apart) in random order. Post-prandial measurements at t = 0 h, t = 2 h and t = 6 h. |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- Healthy male and/or female volunteers, aged between 18 and 70 years
Key exclusion criteria (19 listed)
- they are taking aspirin or aspirin-containing drugs, other anti-inflammatory drugs, or any drugs or herbal medicines known to alter platelet function or the haemostatic system in general (without a minimum washout period of one month)
- they are taking fish oils or evening primrose oil, or fat soluble vitamin supplements within the last 4 weeks
- they are taking any medicine known to affect lipid and/or glucose metabolism
- they are taking hormone replacement therapy
- they have any known clinical signs of diabetes, hypertension, renal, hepatic, hematological disease, gastrointestinal disorders, endocrine disorders, coronary heart disease, infection or cancer
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Dark chocolate enriched in flavan-3-ols and procyanidinsAlso: CocoanOX12%-containing chocolateAcute consumption (within 15 minutes) of 60 g of chocolate containing ~900 mg of total flavan-3-ols and procyanidins. | Dietary supplement | 42 healthy volunteers - crossover |
| Standard dark chocolateAcute consumption (within 15 minutes) of 60 g of chocolate containing ~400 mg total flavan-3-ols and procyanidins. | Dietary supplement | 42 healthy volunteers - crossover |
| White chocolateAcute consumption (within 15 minutes) of 60 g of white chocolate containing no flavan-3-ols and procyanidins. | Dietary supplement | 42 healthy volunteers - crossover |
Primary outcome
Change in light transmission aggregometry of platelet-rich plasma
Time frame: Post-prandial, up to 6 hours after chocolate consumption
* Using a Helena Platelet Aggregation Chromogenic Kinetics System-4 (PACKS-4) light transmission aggregometer * Induced by adenosine diphosphate (ADP) and thrombin receptor-activating peptide (TRAP)
14 secondary outcomes
Change in ex vivo bleeding time using the Platelet Function Analyzer-100 (PFA-100)
Time frame: Post-prandial, up to 6 hours after chocolate consumption
Change in P-selectin expression and activation of the fibrinogen receptor by flow cytometry
Time frame: Post-prandial, up to 6 hours after chocolate consumption
Levels of flavan-3-ols and their metabolites in plasma and urine
Time frame: Post-prandial, up to 6 hours after chocolate consumption
Changes in the platelet proteome
Time frame: Post-prandial, 2 hours after chocolate ingestion
Changes in thromboxane A2 production induced by ADP and TRAP
Time frame: Post-prandial, up to 6 hours after chocolate consumption
Levels of prostacyclin and/ or leukotrienes in plasma
Time frame: Post-prandial, up to 6 hours after chocolate consumption
Total phenolics in urine
Time frame: Post-prandial, up to 6 hours after chocolate consumption
Total catechins in urine
Time frame: Post-prandial, up to 6 hours after chocolate consumption
Urinary creatinine
Time frame: Post-prandial, up to 6 hours after chocolate consumption
Analysis of flavan-3-ol and procyanidin contents in study chocolates
Time frame: At the beginning (April 2009) and end (October 2009) of the intervention period
Non-targeted 1H-NMR of plasma and urine samples
Time frame: Post-prandial, up to 6 hours after chocolate consumption
Non-targeted LC-MS of urine samples
Time frame: Post-prandial, just before and 6 hours after chocolate consumption
Markers of oxidative stress in plasma
Time frame: Post-prandial, up to 6 hours after chocolate consumption
Fatty acid analysis of study chocolates
Time frame: Shortly after the intervention period was finished (February 2009)
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Apr 2012.
- Background: PubMed 11200094Baba S, Osakabe N, Yasuda A, Natsume M, Takizawa T, Nakamura T, Terao J. Bioavailability of (-)-epicatechin upon intake of chocolate and cocoa in human volunteers. Free Radic Res. 2000 Nov;33(5):635-41. doi: 10.1080/10715760000301151.
- Background: PubMed 17917513Bordeaux B, Yanek LR, Moy TF, White LW, Becker LC, Faraday N, Becker DM. Casual chocolate consumption and inhibition of platelet function. Prev Cardiol. 2007 Fall;10(4):175-80. doi: 10.1111/j.1520-037x.2007.06693.x.
- Background: PubMed 18489134de Roos B, Duthie SJ, Polley AC, Mulholland F, Bouwman FG, Heim C, Rucklidge GJ, Johnson IT, Mariman EC, Daniel H, Elliott RM. Proteomic methodological recommendations for studies involving human plasma, platelets, and peripheral blood mononuclear cells. J Proteome Res. 2008 Jun;7(6):2280-90. doi: 10.1021/pr700714x. Epub 2008 May 20.
- Background: PubMed 17984375Flammer AJ, Hermann F, Sudano I, Spieker L, Hermann M, Cooper KA, Serafini M, Luscher TF, Ruschitzka F, Noll G, Corti R. Dark chocolate improves coronary vasomotion and reduces platelet reactivity. Circulation. 2007 Nov 20;116(21):2376-82. doi: 10.1161/CIRCULATIONAHA.107.713867. Epub 2007 Nov 5.
- Background: PubMed 17425630Guerrero JA, Navarro-Nunez L, Lozano ML, Martinez C, Vicente V, Gibbins JM, Rivera J. Flavonoids inhibit the platelet TxA(2) signalling pathway and antagonize TxA(2) receptors (TP) in platelets and smooth muscle cells. Br J Clin Pharmacol. 2007 Aug;64(2):133-44. doi: 10.1111/j.1365-2125.2007.02881.x. Epub 2007 Apr 10.
- Background: PubMed 19005437Hamed MS, Gambert S, Bliden KP, Bailon O, Singla A, Antonino MJ, Hamed F, Tantry US, Gurbel PA. Dark chocolate effect on platelet activity, C-reactive protein and lipid profile: a pilot study. South Med J. 2008 Dec;101(12):1203-8. doi: 10.1097/SMJ.0b013e31818859eb.
- Background: PubMed 16794458Heptinstall S, May J, Fox S, Kwik-Uribe C, Zhao L. Cocoa flavanols and platelet and leukocyte function: recent in vitro and ex vivo studies in healthy adults. J Cardiovasc Pharmacol. 2006;47 Suppl 2:S197-205; discussion S206-9. doi: 10.1097/00005344-200606001-00015.
- Background: PubMed 16365364Hermann F, Spieker LE, Ruschitzka F, Sudano I, Hermann M, Binggeli C, Luscher TF, Riesen W, Noll G, Corti R. Dark chocolate improves endothelial and platelet function. Heart. 2006 Jan;92(1):119-20. doi: 10.1136/hrt.2005.063362. No abstract available.
- Background: PubMed 16925853Hubbard GP, Wolffram S, de Vos R, Bovy A, Gibbins JM, Lovegrove JA. Ingestion of onion soup high in quercetin inhibits platelet aggregation and essential components of the collagen-stimulated platelet activation pathway in man: a pilot study. Br J Nutr. 2006 Sep;96(3):482-8.
- Background: PubMed 15613018Hubbard GP, Wolffram S, Lovegrove JA, Gibbins JM. Ingestion of quercetin inhibits platelet aggregation and essential components of the collagen-stimulated platelet activation pathway in humans. J Thromb Haemost. 2004 Dec;2(12):2138-45. doi: 10.1111/j.1538-7836.2004.01067.x.
- Background: PubMed 12944249Innes AJ, Kennedy G, McLaren M, Bancroft AJ, Belch JJ. Dark chocolate inhibits platelet aggregation in healthy volunteers. Platelets. 2003 Aug;14(5):325-7. doi: 10.1080/0953710031000123681.
- BackgroundMavrommatis Y, O'Kennedy N, de Roos B et al. Effect of eicosapentaenoic acid or docosahexaenoic acid intervention on platelet aggregation: does soluble epoxide hydrolase play a role? unpublished, 2010
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Baukje de Roos, MSc PhD principal investigator
University of Aberdeen Rowett Institute of Nutrition and Health
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Dark chocolate enriched in flavan-3-ols and procyanidins, Standard dark chocolate and White chocolate in people with Cardiovascular Disease, run by University of Aberdeen at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 17 Apr 2012. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in light transmission aggregometry of platelet-rich plasma (time frame: Post-prandial, up to 6 hours after chocolate consumption). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01099150, which also lists 23 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Apr 2012.