Effect of Polyphenols on Peripheral Vascular Disease.

NCT01947712 | Completed Phase 1 DMC

• 1 other identifier: C26A12BPZN
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

Peripheral Arterial Disease

Keywords

Peripheral arterial disease; Oxidative stress; Cocoa; polyphenols; NADPH oxidase

Outcome Measures

Primary Outcomes (2)

• endothelial function assessed by flow mediated dilation (FMD)

  2 hours after (dark or milk) chocolate ingestion

• endothelial function assessed by flow mediated dilation (FMD)

  after 30 days of (dark or milk) chocolate ingestion

Secondary Outcomes (6)

• Oxidative stress markers

  2 hours after (dark or milk) chocolate ingestion

• Maximal walking distance

  2 hours after (dark or milk) chocolate ingestion

• Ankle Brachial Index (ABI)

  2 hours after (dark or milk) chocolate ingestion

• Oxidative stress markers

  after 30 days of (dark or milk) chocolate ingestion

• Maximal walking distance

  after 30 days of (dark or milk) chocolate ingestion

Study Arms (2)

milk chocolate

PLACEBO COMPARATOR

dosage form: orally given dosage:40 g milk chocolate (≤35% cocoa) frequency and duration: 40 g/day for one month

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

Dietary Supplement: dark chocolate with crossover to milk chocolate

Interventions

dark chocolate with crossover to milk chocolate DIETARY_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

dark chocolate

milk chocolate with crossover to dark chocolate DIETARY_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.

milk chocolate

Eligibility Criteria

• Age: 20 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Roma La Sapienza: lead

Study Sites (1)

Sapienza University of Rome, I Clinica Medica, Research Tower

Rome, 00161, Italy

Location

Related Publications (4)

• 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.

  PMID: 22336250 BACKGROUND

• Carnevale 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.

  PMID: 22066819 BACKGROUND

• Loffredo 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.

  PMID: 21807659 BACKGROUND

• Loffredo 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.

  PMID: 24990275 DERIVED

MeSH Terms

Conditions

Peripheral Arterial Disease

Condition Hierarchy (Ancestors)

Atherosclerosis; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Cardiovascular Diseases; Peripheral Vascular Diseases

Study Officials

• Francesco Violi, MD

  Sapienza University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Full professor of Internal Medicine

Study Record Dates

• First Submitted: September 12, 2013
• First Posted: September 20, 2013
• Study Start: October 1, 2010
• Primary Completion: August 1, 2013
• Study Completion: September 1, 2013
• Last Updated: September 20, 2013

Record last verified: 2013-09

Locations

IT (1)