Peripheral Arterial DiseasePhase 1/2NCT01947712
Effect of Polyphenols on Peripheral Vascular Disease.
A Phase 1/2 study testing dark chocolate with crossover to milk chocolate and milk chocolate with crossover to dark chocolate in people with Peripheral Arterial Disease, run by University of Roma La Sapienza at 1 site in Italy.
Trial summary
Peripheral arterial disease (PAD) is a clinical setting characterized by an exceptionally high risk for cardiovascular events. Oxidative stress seems to play a role in impairing flow-mediated dilation (FMD) and contributing to atherosclerosis in patients with PAD. Read more about this study
- Who is it for?
- Ages 20 to 90 years
- Conditions the study is for
- Peripheral Arterial Disease
- What is being tested?
- dark chocolate with crossover to milk chocolate and milk chocolate with crossover to dark chocolate
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 20 participants
- Where
- 1 siteItaly
- Study dates
- Oct 2010to Sep 2013
- Phase
- Phase 1/2
- 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 20 to 90 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Every PAD patient to be enrolled in the study had:
- claudication (defined as leg pain on walking, disappearing within 10 minutes of standing, of presumed atherosclerotic origin) and
- ankle/brachial index (ABI), that was assessed as ankle/arm systolic blood pressure ratio by Doppler ultrasonography <0.90 on the worst leg at rest.
- Patients had to be in stable conditions without abrupt changes of ABI (>20%) in the last month before the enrolment.
Who cannot join
- Subjects were excluded from the study if they had liver insufficiency, serious renal disorders (serum creatinine>2.8 mg/dL), acute stroke, acute myocardial infarction, deep venous thrombosis or if they were current smokers or were taking antioxidants.
Trial locations and contacts
1 site in 1 country.
Italy1 site
Sapienza University of Rome, I Clinica Medica, Research Tower
Rome, 00161
About this study
Official title: Effect of Dark Chocolate on Endothelial Function and Oxidative Stress in Patients With Peripheral Vascular Disease.
Peripheral arterial disease (PAD) is a clinical setting characterized by an exceptionally high risk for cardiovascular events. Oxidative stress seems to play a role in impairing flow-mediated dilation (FMD) and contributing to atherosclerosis in patients with PAD. Cocoa seems to exert artery dilatation via oxidative stress inhibition.
OBJECTIVES: To investigate whether in PAD patients, dark chocolate elicits artery dilatation via down-regulation of NOX2, the catalytic core of NADPH oxidase.
Read the detailed description
Atherosclerosis represents the major cause of worldwide death; it is a complex phenomenon that encompasses the intricate interplay of classic cardiovascular risk factors, oxidative stress and inflammation.
Peripheral artery disease (PAD) is a clinical setting that well represents the model of widespread atherosclerosis. PAD affects 20% of patients over the age of 75. Furthermore, PAD patients are at an exceptionally high risk for cardiovascular events and the majority will eventually die of a cardiac or cerebrovascular etiology.
Polyphenol could represent a novel therapeutic strategy to counteract atherosclerosis. During the last decades, a growing interest in polyphenols resulted from prospective and epidemiological studies that showed the beneficial effects of these substances on human health. In particular, polyphenols exert their beneficial effect by inhibition of NADPH oxidase (NOX2), an enzyme directly involved in atherosclerosis; thus, the activation of this enzyme leads to an enhanced production of oxidative stress and inflammatory processes.
The objective of this study is to evaluate the effect of polyphenols on oxidative stress and inflammation and on surrogate markers of atherosclerosis in PAD patients. Polyphenols, inhibiting NOX2-mediated oxidative stress and immune-mediated process, could represent a novel therapy to reduce the high risk of cardiovascular events in PAD.
- Conditions
- Peripheral Arterial Disease
- Being tested
- dark chocolate with crossover to milk chocolate, milk chocolate with crossover to dark chocolate
- Keywords
- Peripheral arterial disease, Oxidative stress, Cocoa, polyphenols, NADPH oxidase
- Medical subject headings
- Peripheral Arterial Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
dark chocolate with crossover to milk chocolateDietary supplement
40 g/d of dark chocolate for 4 weeks followed by wash-out (1 week) and by 40 g/d of milk chocolate for 4 weeks
milk chocolate with crossover to dark chocolateDietary supplement
40 g/d of milk chocolate for 4 weeks followed by wash-out (1 week) and by 40 g/d of dark chocolate for 4 weeks.
| Study group | Role | What they receive |
|---|---|---|
| milk chocolate | Placebo comparator | dosage form: orally given dosage:40 g milk chocolate (≤35% cocoa) frequency and duration: 40 g/day for one month Receives: Dietary Supplement: milk chocolate with crossover to dark chocolate |
| dark chocolate | Active comparator | dosage form: orally given dosage:40 g dark chocolate (≥85% cocoa) frequency and duration: 40 g/day for one month Receives: Dietary Supplement: dark chocolate with crossover to milk chocolate |
What is being measured
The primary outcome is the main question the study is designed to answer.
endothelial function assessed by flow mediated dilation (FMD)
Measured: 2 hours after (dark or milk) chocolate ingestion
endothelial function assessed by flow mediated dilation (FMD)
Measured: after 30 days of (dark or milk) chocolate ingestion
Secondary outcomes (6)
Oxidative stress markers
Oxidative stress markers: sNOX2dp, Isoprostanes, NOx
Measured: 2 hours after (dark or milk) chocolate ingestion
Maximal walking distance
Measured: 2 hours after (dark or milk) chocolate ingestion
Ankle Brachial Index (ABI)
Measured: 2 hours after (dark or milk) chocolate ingestion
Oxidative stress markers
Oxidative stress markers: sNOX2dp, Isoprostanes, NOx
Measured: after 30 days of (dark or milk) chocolate ingestion
Maximal walking distance
Measured: after 30 days of (dark or milk) chocolate ingestion
Ankle Brachial Index (ABI)
Measured: after 30 days of (dark or milk) chocolate ingestion
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Sep 2013 (estimated)
- Study startOct 2010
- Primary completionAug 2013
- Study completionSep 2013
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 Peripheral Arterial DiseaseStudies of the same condition, open and under way.
- More trials run by University of Roma La SapienzaThe sponsor's other registered studies.
- 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 1/2
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Roma La Sapienza
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Francesco Violi, University of Roma La Sapienza
- Investigators
- Francesco Violi, MD, Principal investigator, Sapienza University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01947712
- Sponsor's protocol ID
- C26A12BPZN
- Other IDs
- C26A12BPZN
- Status last verified
- Sep 2013
- First submitted
- 12 Sep 2013
- Last updated
- 20 Sep 2013
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Loffredo L, Carnevale R, Cangemi R, Angelico F, Augelletti T, Di Santo S, Calabrese CM, Della Volpe L, Pignatelli P, Perri L, Basili S, Violi F. NOX2 up-regulation is associated with artery dysfunction in patients with peripheral artery disease. Int J Cardiol. 2013 Apr 30;165(1):184-92. doi: 10.1016/j.ijcard.2012.01.069. Epub 2012 Feb 14.
PubMed 22336250Carnevale R, Loffredo L, Pignatelli P, Nocella C, Bartimoccia S, Di Santo S, Martino F, Catasca E, Perri L, Violi F. Dark chocolate inhibits platelet isoprostanes via NOX2 down-regulation in smokers. J Thromb Haemost. 2012 Jan;10(1):125-32. doi: 10.1111/j.1538-7836.2011.04558.x.
PubMed 22066819Loffredo L, Carnevale R, Perri L, Catasca E, Augelletti T, Cangemi R, Albanese F, Piccheri C, Nocella C, Pignatelli P, Violi F. NOX2-mediated arterial dysfunction in smokers: acute effect of dark chocolate. Heart. 2011 Nov;97(21):1776-81. doi: 10.1136/heartjnl-2011-300304. Epub 2011 Jul 31.
PubMed 21807659Loffredo L, Perri L, Catasca E, Pignatelli P, Brancorsini M, Nocella C, De Falco E, Bartimoccia S, Frati G, Carnevale R, Violi F. Dark chocolate acutely improves walking autonomy in patients with peripheral artery disease. J Am Heart Assoc. 2014 Jul 2;3(4):e001072. doi: 10.1161/JAHA.114.001072.
PubMed 24990275
Study at a glance
From the registry record, last updated by the sponsor on 20 Sep 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Dark Chocolate on Endothelial Function and Oxidative Stress in Patients With Peripheral Vascular Disease.
- ClinicalTrials.gov ID
- NCT01947712
- Acronym / sponsor ID
- C26A12BPZN
- Conditions
- Peripheral Arterial Disease
- Keywords
- Peripheral arterial disease, Oxidative stress, Cocoa, polyphenols, NADPH oxidase
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- University of Roma La SapienzaUniversity, hospital or other
- Study start
- Oct 2010
- Primary completion
- Aug 2013 (actual)
- Study completion
- Sep 2013 (actual)
- First posted
- 20 Sep 2013 (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.
Peripheral arterial disease (PAD) is a clinical setting characterized by an exceptionally high risk for cardiovascular events. Oxidative stress seems to play a role in impairing flow-mediated dilation (FMD) and contributing to atherosclerosis in patients with PAD. Cocoa seems to exert artery dilatation via oxidative stress inhibition.
OBJECTIVES: To investigate whether in PAD patients, dark chocolate elicits artery dilatation via down-regulation of NOX2, the catalytic core of NADPH oxidase.
Detailed description
Atherosclerosis represents the major cause of worldwide death; it is a complex phenomenon that encompasses the intricate interplay of classic cardiovascular risk factors, oxidative stress and inflammation.
Peripheral artery disease (PAD) is a clinical setting that well represents the model of widespread atherosclerosis. PAD affects 20% of patients over the age of 75. Furthermore, PAD patients are at an exceptionally high risk for cardiovascular events and the majority will eventually die of a cardiac or cerebrovascular etiology.
Polyphenol could represent a novel therapeutic strategy to counteract atherosclerosis. During the last decades, a growing interest in polyphenols resulted from prospective and epidemiological studies that showed the beneficial effects of these substances on human health. In particular, polyphenols exert their beneficial effect by inhibition of NADPH oxidase (NOX2), an enzyme directly involved in atherosclerosis; thus, the activation of this enzyme leads to an enhanced production of oxidative stress and inflammatory processes.
The objective of this study is to evaluate the effect of polyphenols on oxidative stress and inflammation and on surrogate markers of atherosclerosis in PAD patients. Polyphenols, inhibiting NOX2-mediated oxidative stress and immune-mediated process, could represent a novel therapy to reduce the high risk of cardiovascular events in PAD.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| milk chocolate | Placebo comparator | Dietary Supplement: milk chocolate with crossover to dark chocolatedosage form: orally given dosage:40 g milk chocolate (≤35% cocoa) frequency and duration: 40 g/day for one month |
| dark chocolate | Active comparator | Dietary Supplement: dark chocolate with crossover to milk chocolatedosage form: orally given dosage:40 g dark chocolate (≥85% cocoa) frequency and duration: 40 g/day for one month |
Who may qualify
- Ages
- 20 to 90 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- claudication (defined as leg pain on walking, disappearing within 10 minutes of standing, of presumed atherosclerotic origin) and
- ankle/brachial index (ABI), that was assessed as ankle/arm systolic blood pressure ratio by Doppler ultrasonography <0.90 on the worst leg at rest.
- Patients had to be in stable conditions without abrupt changes of ABI (>20%) in the last month before the enrolment.
Key exclusion criteria (1 listed)
- Subjects were excluded from the study if they had liver insufficiency, serious renal disorders (serum creatinine>2.8 mg/dL), acute stroke, acute myocardial infarction, deep venous thrombosis or if they were current smokers or were taking antioxidants.
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 with crossover to milk chocolate40 g/d of dark chocolate for 4 weeks followed by wash-out (1 week) and by 40 g/d of milk chocolate for 4 weeks | Dietary supplement | dark chocolate |
| milk chocolate with crossover to dark chocolate40 g/d of milk chocolate for 4 weeks followed by wash-out (1 week) and by 40 g/d of dark chocolate for 4 weeks. | Dietary supplement | milk chocolate |
Primary outcome
endothelial function assessed by flow mediated dilation (FMD)
Time frame: 2 hours after (dark or milk) chocolate ingestion
endothelial function assessed by flow mediated dilation (FMD)
Time frame: after 30 days of (dark or milk) chocolate ingestion
6 secondary outcomes
Oxidative stress markers
Time frame: 2 hours after (dark or milk) chocolate ingestion
Maximal walking distance
Time frame: 2 hours after (dark or milk) chocolate ingestion
Ankle Brachial Index (ABI)
Time frame: 2 hours after (dark or milk) chocolate ingestion
Oxidative stress markers
Time frame: after 30 days of (dark or milk) chocolate ingestion
Maximal walking distance
Time frame: after 30 days of (dark or milk) chocolate ingestion
Ankle Brachial Index (ABI)
Time frame: after 30 days of (dark or milk) chocolate ingestion
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 20 Sep 2013.
- Background: PubMed 22336250Loffredo L, Carnevale R, Cangemi R, Angelico F, Augelletti T, Di Santo S, Calabrese CM, Della Volpe L, Pignatelli P, Perri L, Basili S, Violi F. NOX2 up-regulation is associated with artery dysfunction in patients with peripheral artery disease. Int J Cardiol. 2013 Apr 30;165(1):184-92. doi: 10.1016/j.ijcard.2012.01.069. Epub 2012 Feb 14.
- Background: PubMed 22066819Carnevale R, Loffredo L, Pignatelli P, Nocella C, Bartimoccia S, Di Santo S, Martino F, Catasca E, Perri L, Violi F. Dark chocolate inhibits platelet isoprostanes via NOX2 down-regulation in smokers. J Thromb Haemost. 2012 Jan;10(1):125-32. doi: 10.1111/j.1538-7836.2011.04558.x.
- Background: PubMed 21807659Loffredo L, Carnevale R, Perri L, Catasca E, Augelletti T, Cangemi R, Albanese F, Piccheri C, Nocella C, Pignatelli P, Violi F. NOX2-mediated arterial dysfunction in smokers: acute effect of dark chocolate. Heart. 2011 Nov;97(21):1776-81. doi: 10.1136/heartjnl-2011-300304. Epub 2011 Jul 31.
- Derived from this study: PubMed 24990275Loffredo L, Perri L, Catasca E, Pignatelli P, Brancorsini M, Nocella C, De Falco E, Bartimoccia S, Frati G, Carnevale R, Violi F. Dark chocolate acutely improves walking autonomy in patients with peripheral artery disease. J Am Heart Assoc. 2014 Jul 2;3(4):e001072. doi: 10.1161/JAHA.114.001072.
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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.
Francesco Violi, MD principal investigator
Sapienza University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing dark chocolate with crossover to milk chocolate and milk chocolate with crossover to dark chocolate in people with Peripheral Arterial Disease, run by University of Roma La Sapienza at 1 site in Italy.
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 4 inclusion and 1 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 20 Sep 2013. 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 Italy. 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. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined 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.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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.
What does the primary outcome measure?
endothelial function assessed by flow mediated dilation (FMD) (time frame: 2 hours after (dark or milk) chocolate ingestion). The study lists 2 primary outcomes in all. 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 NCT01947712, 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 20 Sep 2013.