HypertensionPhase 1NCT00099476
Effects of Dark Chocolate on Insulin Sensitivity in People With High Blood Pressure
A Phase 1 study testing Effects of dark chocolate in people with Hypertension, run by National Center for Complementary and Integrative Health (NCCIH) at 1 site in United States.
Trial summary
This study will examine whether dark chocolate affects the way patients with hypertension (high blood pressure) respond to insulin, a hormone secreted by the pancreas that regulates blood glucose (sugar) levels. In many people with hypertension, insulin is not as effective in helping the body use glucose. Read more about this study
- Who is it for?
- Ages 21 to 65 years
- Conditions the study is for
- Hypertension
- What is being tested?
- Effects of dark chocolate
- Type of treatment
- Lifestyle or therapy programme
- How many people
- 65 participants
- Where
- 1 siteUnited States
- Study dates
- 10 Dec 2004to 16 Apr 2009
- Phase
- Phase 1
- 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 21 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Hypertensive subjects between the ages of 21 - 65 years in good general health except for mild to moderate hypertension (blood pressure between 140/95 and 170/110 off medication), on no medication or nutritional supplements except for antihypertensive agents, anti-cholesterol drugs or birth control agents. Subjects will be taken off all antihypertensive OTC supplements and anti-cholesterol drugs for one week prior to study and for the duration of the study. Women on birth control will remain on their regime. During the time subjects receive no antihypertensive therapy, their blood pressure will be monitored at least daily (either at home, in the clinic, or at another convenient facility). If a subject's blood pressure exceeds 170/110 on three determinations over a period of at least 15 minutes, the subject will be withdrawn from the study and appropriate antihypertensive therapy resumed. In addition, if the subject's blood pressure exceeds 160/100 during measurements on three consecutive days, the subject will be withdrawn from the study and appropriate antihypertensive therapy resumed.
Who cannot join
- Subjects will be excluded if they have diabetes, pregnancy, liver disease, pulmonary disease, renal insufficiency, coronary heart disease, heart failure, peripheral vascular disease, coagulopathy, actively smoked tobacco within last two years, in treatment for any form of cancer, positive tests for HIV, hepatitis B or C, or take systemic corticosteroids. These conditions are all known to adversely influence insulin sensitivity.
- Subjects will be excluded if they have a history of malignant hypertension, aortic aneurysm or stroke.
- Subjects with known hypersensitivity to octafluoropropane or with known cardiac shunts will also be excluded from participating because of potential adverse effects from microbubble contrast agent.
- Subjects will be excluded if they are unable to give informed consent for all procedures.
- Children are excluded from this study because children are not typically hypertensive.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, 20892
About this study
Official title: Effects of Cocoa Consumption on Insulin Sensitivity and Capillary Recruitment in Subjects With Essential Hypertension
This study will examine whether dark chocolate affects the way patients with hypertension (high blood pressure) respond to insulin, a hormone secreted by the pancreas that regulates blood glucose (sugar) levels. In many people with hypertension, insulin is not as effective in helping the body use glucose. This is called insulin resistance. Insulin also increases blood flow into muscle by opening inactive blood vessels. Laboratory studies suggest that eating dark chocolate may improve blood pressure. This study will determine whether dark chocolate improves insulin resistance or changes how blood vessels react to insulin in hypertensive people.
People between 21 and 65 years of age who have high blood pressure and are not pregnant may be eligible for this study. Candidates are screened with a medical history, physical examination, and blood and urine tests.
Read more
Participants refrain from eating foods containing chocolate or cocoa for 1 week and then come to the clinic on three separate occasions 3 weeks apart for a glucose clamp test and contrast ultrasound, described below. At the first glucose clamp test, subjects are randomly assigned to drink either a cocoa drink with high anti-oxidant content or one with a very low content of anti-oxidant. Each drink will be taken twice a day for 2 weeks. At the end of the 2 weeks, they return for a second glucose clamp test. At the second test, they stop taking the cocoa drink for 1 week and then start again for another 2 weeks. For this 2-week period, those who were given the high anti-oxidant content cocoa drink the first 2 weeks will take the placebo, very low anti-oxidant drink this time, and those who took the placebo will now have the high anti-oxidant cocoa drink. After this 2 weeks of taking the cocoa drink or placebo, they then take the third and last glucose clamp test.
Glucose clamp test: This test measures how the body responds to insulin. Subjects fast the night before each test and do not eat until the test is over, usually in the early afternoon. For the test, the subject lies in a bed or reclines in a chair. A needle is placed in a vein in each arm - one for collecting blood samples and the other for infusing glucose, insulin, and a potassium solution. Blood glucose and insulin levels are measured frequently during the test and the rate of the glucose infusion is adjusted to keep blood glucose at the baseline (fasting) level. Blood samples are tested for blood count, electrolytes, liver function...
Read the detailed description
Dark chocolate and other cocoa products contain antioxidants including the polyphenol epicatechin that have beneficial effects on vascular function. Oral consumption of dark chocolate lowers blood pressure in elderly subjects with isolated systolic hypertension while drinking cocoa acutely improves flow-mediated vasodilation in subjects with cardiovascular risk factors. Work from our lab and elsewhere has shown that regulation of hemodynamic and metabolic homeostasis are coupled such that subjects with essential hypertension are also insulin resistant. Therefore, we hypothesize that cocoa consumption will improve both blood pressure and insulin sensitivity in subjects with essential hypertension. To test this hypothesis, we will conduct a randomized double-blind, crossover study in subjects with essential hypertension to evaluate the effects of cocoa versus placebo on blood pressure, insulin sensitivity, and insulin-mediated capillary recruitment in skeletal muscle. After a 7 day cocoa-free run-in period, subjects will be randomized to receive 15 consecutive daily doses of either cocoa drink (150 ml twice a day with a total of 900 mg of polyphenols and 237 kcal) or polyphenol poor placebo drink (150 ml twice a day with a total of 36 mg of polyphenols and 234 kcal). After the 15 day treatment period, the subjects will enter a 1 week cocoa-free washout period followed by cross-over to the other treatment. Subjects will be counseled to maintain an isocaloric diet during the study. Blood pressure, insulin sensitivity, and insulin-mediated capillary recruitment will be assessed in each subject after the run-in period, after 15 days of treatment, and after completion of the cross-over. Blood pressure will also be measured every Monday, Wednesday, and Friday for the duration of the study. Insulin sensitivity will be measured using the hyperinsulinemic euglycemic glucose clamp technique. Insulin-stimulated capillary recruitment in forearm skeletal muscle will be measured by ultrasound with "microbubble" contrast during the glucose clamp studies. Peak and trough plasma epicatechin levels will be measured prior to each glucose clamp study using an HPLC assay. This study will determine if short-term oral administration of cocoa is effective at lowering blood pressure, improving insulin sensitivity, and restoring vascular function in subjects with essential hypertension. This is highly relevant to major public health problems such as diabetes, obesity, hypertension, and cardiovascular diseases where insulin resistance and vascular dysfunction are important pathophysiological components.
- Conditions
- Hypertension
- Being tested
- Effects of dark chocolate
- Keywords
- Epicatechin, Polyphenols, Chocolate, Insulin Resistance, Endothelial Dysfunction, Hypertension
- Medical subject headings
- Hypertension, Insulin Resistance
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Effects of dark chocolateBehavioural
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Dec 2004 (estimated)
- Study start10 Dec 2004
- Study completion16 Apr 2009
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for HypertensionStudies 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 1
- Primary purpose
- Treatment
- Enrolment
- 65 participants
Sponsor and investigators
- Lead sponsor
- National Center for Complementary and Integrative Health (NCCIH)
- Sponsor type
- US National Institutes of Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00099476
- Sponsor's protocol ID
- 050047
- Other IDs
- 05-AT-0047
- Status last verified
- 16 Apr 2009
- First submitted
- 14 Dec 2004
- Last updated
- 2 Jul 2017
- Results posted
- No
Publications
Ferrannini E, Buzzigoli G, Bonadonna R, Giorico MA, Oleggini M, Graziadei L, Pedrinelli R, Brandi L, Bevilacqua S. Insulin resistance in essential hypertension. N Engl J Med. 1987 Aug 6;317(6):350-7. doi: 10.1056/NEJM198708063170605.
PubMed 3299096Modan M, Halkin H, Almog S, Lusky A, Eshkol A, Shefi M, Shitrit A, Fuchs Z. Hyperinsulinemia. A link between hypertension obesity and glucose intolerance. J Clin Invest. 1985 Mar;75(3):809-17. doi: 10.1172/JCI111776.
PubMed 3884667Zavaroni I, Mazza S, Dall'Aglio E, Gasparini P, Passeri M, Reaven GM. Prevalence of hyperinsulinaemia in patients with high blood pressure. J Intern Med. 1992 Mar;231(3):235-40. doi: 10.1111/j.1365-2796.1992.tb00529.x.
PubMed 1556520Muniyappa R, Hall G, Kolodziej TL, Karne RJ, Crandon SK, Quon MJ. Cocoa consumption for 2 wk enhances insulin-mediated vasodilatation without improving blood pressure or insulin resistance in essential hypertension. Am J Clin Nutr. 2008 Dec;88(6):1685-96. doi: 10.3945/ajcn.2008.26457.
PubMed 19064532
Study at a glance
From the registry record, last updated by the sponsor on 2 Jul 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effects of Cocoa Consumption on Insulin Sensitivity and Capillary Recruitment in Subjects With Essential Hypertension
- ClinicalTrials.gov ID
- NCT00099476
- Acronym / sponsor ID
- 050047
- Conditions
- Hypertension
- Keywords
- Epicatechin, Polyphenols, Chocolate, Insulin Resistance, Endothelial Dysfunction, Hypertension
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 65 participants
- Lead sponsor
- National Center for Complementary and Integrative Health (NCCIH)US National Institutes of Health
- Study start
- 10 Dec 2004
- Study completion
- 16 Apr 2009
- First posted
- 15 Dec 2004 (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.
This study will examine whether dark chocolate affects the way patients with hypertension (high blood pressure) respond to insulin, a hormone secreted by the pancreas that regulates blood glucose (sugar) levels. In many people with hypertension, insulin is not as effective in helping the body use glucose. This is called insulin resistance. Insulin also increases blood flow into muscle by opening inactive blood vessels. Laboratory studies suggest that eating dark chocolate may improve blood pressure. This study will determine whether dark chocolate improves insulin resistance or changes how blood vessels react to insulin in hypertensive people.
People between 21 and 65 years of age who have high blood pressure and are not pregnant may be eligible for this study. Candidates are screened with a medical history, physical examination, and blood and urine tests.
Participants refrain from eating foods containing chocolate or cocoa for 1 week and then come to the clinic on three separate occasions 3 weeks apart for a glucose clamp test and contrast ultrasound, described below. At the first glucose clamp test, subjects are randomly assigned to drink either a cocoa drink with high anti-oxidant content or one with a very low content of anti-oxidant. Each drink will be taken twice a day for 2 weeks. At the end of the 2 weeks, they return for a second glucose clamp test. At the second test, they stop taking the cocoa drink for 1 week and then start again for another 2 weeks. For this 2-week period, those who were given the high anti-oxidant content cocoa drink the first 2 weeks will take the placebo, very low anti-oxidant drink this time, and those who took the placebo will now have the high anti-oxidant cocoa drink. After this 2 weeks of taking the cocoa drink or placebo, they then take the third and last glucose clamp test.
Glucose clamp test: This test measures how the body responds to insulin. Subjects fast the night before each test and do not eat until the test is over, usually in the early afternoon. For the test, the subject lies in a bed or reclines in a chair. A needle is placed in a vein in each arm - one for collecting blood samples and the other for infusing glucose, insulin, and a potassium solution. Blood glucose and insulin levels are measured frequently during the test and the rate of the glucose infusion is adjusted to keep blood glucose at the baseline (fasting) level. Blood samples are tested for blood count, electrolytes, liver function...
Detailed description
Dark chocolate and other cocoa products contain antioxidants including the polyphenol epicatechin that have beneficial effects on vascular function. Oral consumption of dark chocolate lowers blood pressure in elderly subjects with isolated systolic hypertension while drinking cocoa acutely improves flow-mediated vasodilation in subjects with cardiovascular risk factors. Work from our lab and elsewhere has shown that regulation of hemodynamic and metabolic homeostasis are coupled such that subjects with essential hypertension are also insulin resistant. Therefore, we hypothesize that cocoa consumption will improve both blood pressure and insulin sensitivity in subjects with essential hypertension. To test this hypothesis, we will conduct a randomized double-blind, crossover study in subjects with essential hypertension to evaluate the effects of cocoa versus placebo on blood pressure, insulin sensitivity, and insulin-mediated capillary recruitment in skeletal muscle. After a 7 day cocoa-free run-in period, subjects will be randomized to receive 15 consecutive daily doses of either cocoa drink (150 ml twice a day with a total of 900 mg of polyphenols and 237 kcal) or polyphenol poor placebo drink (150 ml twice a day with a total of 36 mg of polyphenols and 234 kcal). After the 15 day treatment period, the subjects will enter a 1 week cocoa-free washout period followed by cross-over to the other treatment. Subjects will be counseled to maintain an isocaloric diet during the study. Blood pressure, insulin sensitivity, and insulin-mediated capillary recruitment will be assessed in each subject after the run-in period, after 15 days of treatment, and after completion of the cross-over. Blood pressure will also be measured every Monday, Wednesday, and Friday for the duration of the study. Insulin sensitivity will be measured using the hyperinsulinemic euglycemic glucose clamp technique. Insulin-stimulated capillary recruitment in forearm skeletal muscle will be measured by ultrasound with "microbubble" contrast during the glucose clamp studies. Peak and trough plasma epicatechin levels will be measured prior to each glucose clamp study using an HPLC assay. This study will determine if short-term oral administration of cocoa is effective at lowering blood pressure, improving insulin sensitivity, and restoring vascular function in subjects with essential hypertension. This is highly relevant to major public health problems such as diabetes, obesity, hypertension, and cardiovascular diseases where insulin resistance and vascular dysfunction are important pathophysiological components.
Study design
- Primary purpose
- Treatment
Who may qualify
- Ages
- 21 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- Hypertensive subjects between the ages of 21 - 65 years in good general health except for mild to moderate hypertension (blood pressure between 140/95 and 170/110 off medication), on no medication or nutritional supplements except for antihypertensive agents, anti-cholesterol drugs or birth control agents. Subjects will be taken off all antihypertensive OTC supplements and anti-cholesterol drugs for one week prior to study and for the duration of the study. Women on birth control will remain on their regime. During the time subjects receive no antihypertensive therapy, their blood pressure will be monitored at least daily (either at home, in the clinic, or at another convenient facility). If a subject's blood pressure exceeds 170/110 on three determinations over a period of at least 15 minutes, the subject will be withdrawn from the study and appropriate antihypertensive therapy resumed. In addition, if the subject's blood pressure exceeds 160/100 during measurements on three consecutive days, the subject will be withdrawn from the study and appropriate antihypertensive therapy resumed.
Key exclusion criteria (5 listed)
- Subjects will be excluded if they have diabetes, pregnancy, liver disease, pulmonary disease, renal insufficiency, coronary heart disease, heart failure, peripheral vascular disease, coagulopathy, actively smoked tobacco within last two years, in treatment for any form of cancer, positive tests for HIV, hepatitis B or C, or take systemic corticosteroids. These conditions are all known to adversely influence insulin sensitivity.
- Subjects will be excluded if they have a history of malignant hypertension, aortic aneurysm or stroke.
- Subjects with known hypersensitivity to octafluoropropane or with known cardiac shunts will also be excluded from participating because of potential adverse effects from microbubble contrast agent.
- Subjects will be excluded if they are unable to give informed consent for all procedures.
- Children are excluded from this study because children are not typically hypertensive.
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 |
|---|---|---|
| Effects of dark chocolate | Behavioural | – |
Primary outcome
Not reported in the source record.
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 2 Jul 2017.
- Background: PubMed 3299096Ferrannini E, Buzzigoli G, Bonadonna R, Giorico MA, Oleggini M, Graziadei L, Pedrinelli R, Brandi L, Bevilacqua S. Insulin resistance in essential hypertension. N Engl J Med. 1987 Aug 6;317(6):350-7. doi: 10.1056/NEJM198708063170605.
- Background: PubMed 3884667Modan M, Halkin H, Almog S, Lusky A, Eshkol A, Shefi M, Shitrit A, Fuchs Z. Hyperinsulinemia. A link between hypertension obesity and glucose intolerance. J Clin Invest. 1985 Mar;75(3):809-17. doi: 10.1172/JCI111776.
- Background: PubMed 1556520Zavaroni I, Mazza S, Dall'Aglio E, Gasparini P, Passeri M, Reaven GM. Prevalence of hyperinsulinaemia in patients with high blood pressure. J Intern Med. 1992 Mar;231(3):235-40. doi: 10.1111/j.1365-2796.1992.tb00529.x.
- Derived from this study: PubMed 19064532Muniyappa R, Hall G, Kolodziej TL, Karne RJ, Crandon SK, Quon MJ. Cocoa consumption for 2 wk enhances insulin-mediated vasodilatation without improving blood pressure or insulin resistance in essential hypertension. Am J Clin Nutr. 2008 Dec;88(6):1685-96. doi: 10.3945/ajcn.2008.26457.
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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.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Effects of dark chocolate in people with Hypertension, run by National Center for Complementary and Integrative Health (NCCIH) at 1 site in United States.
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 5 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 2 Jul 2017. 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 States. 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.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
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.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00099476, which also lists 4 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 2 Jul 2017.