Effect of Polyphenols on Peripheral Vascular Disease.

Peripheral Arterial Disease Clinical Trial

Official title:

Effect of Dark Chocolate on Endothelial Function and Oxidative Stress in Patients With Peripheral Vascular Disease.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01947712
• Other study ID #: C26A12BPZN
• Secondary ID: C26A12BPZN
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: September 12, 2013
• Last updated: September 17, 2013
• Start date: October 2010
• Est. completion date: September 2013

Study information

• Verified date: September 2013
• Source: University of Roma La Sapienza
• Contact: n/a
• Is FDA regulated: No
• Health authority: Italy: Ethics Committee
• Study type: Interventional

Clinical 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. 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 20
• Est. completion date: September 2013
• Est. primary completion date: August 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 20 Years to 90 Years

Eligibility

Inclusion Criteria:

Every PAD patient to be enrolled in the study had:

1. claudication (defined as leg pain on walking, disappearing within 10 minutes of standing, of presumed atherosclerotic origin) and

2. 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.

Exclusion Criteria:

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.

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Crossover Assignment, Masking: Single Blind (Outcomes Assessor), Primary Purpose: Basic Science

Related Conditions & MeSH terms

• Peripheral Arterial Disease
• Peripheral Vascular Diseases
• Vascular Diseases

Intervention

Dietary Supplement:
• dark chocolate with crossover to milk chocolate
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 chocolate
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.

Locations

Country	Name	City	State
Italy	Sapienza University of Rome, I Clinica Medica, Research Tower	Rome

Sponsors (1)

Lead Sponsor	Collaborator
University of Roma La Sapienza

Country where clinical trial is conducted

Italy, 

References & Publications (3)

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. — View Citation

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	endothelial function assessed by flow mediated dilation (FMD)		2 hours after (dark or milk) chocolate ingestion	No
Primary	endothelial function assessed by flow mediated dilation (FMD)		after 30 days of (dark or milk) chocolate ingestion	No
Secondary	Oxidative stress markers	Oxidative stress markers: sNOX2dp, Isoprostanes, NOx	2 hours after (dark or milk) chocolate ingestion	No
Secondary	Maximal walking distance		2 hours after (dark or milk) chocolate ingestion	No
Secondary	Ankle Brachial Index (ABI)		2 hours after (dark or milk) chocolate ingestion	No
Secondary	Oxidative stress markers	Oxidative stress markers: sNOX2dp, Isoprostanes, NOx	after 30 days of (dark or milk) chocolate ingestion	No
Secondary	Maximal walking distance		after 30 days of (dark or milk) chocolate ingestion	No
Secondary	Ankle Brachial Index (ABI)		after 30 days of (dark or milk) chocolate ingestion	No