Effect of Polyphenols on Peripheral Vascular Disease.

Phase 1

Completed

• Conditions: Peripheral Arterial Disease
• Interventions: Dietary Supplement: milk chocolate with crossover to dark chocolate; Dietary Supplement: dark chocolate with crossover to milk chocolate

• Registration Number: NCT01947712
• Lead Sponsor: University of Roma La Sapienza

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.

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 Timeline

• Study Start: 2010-10
• Primary Completion: 2013-08
• Status Verified: 2013-09
• Study Completion: 2013-09
• Study First Submitted: 2013-09-12
• Study First Submitted QC: 2013-09-17
• Last Update Submitted: 2013-09-17
• Study First Posted: 2013-09-20
• Last Update Posted: 2013-09-20

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 20

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

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
milk chocolate	milk chocolate with crossover to dark chocolate	dosage form: orally given dosage:40 g milk chocolate (≤35% cocoa) frequency and duration: 40 g/day for one month
dark chocolate	dark chocolate with crossover to milk chocolate	dosage form: orally given dosage:40 g dark chocolate (≥85% cocoa) frequency and duration: 40 g/day for one month

Primary Outcome Measures

Name	Time	Method
endothelial function assessed by flow mediated dilation (FMD)	after 30 days of (dark or milk) chocolate ingestion

Secondary Outcome Measures

Name	Time	Method
Oxidative stress markers	after 30 days of (dark or milk) chocolate ingestion	Oxidative stress markers: sNOX2dp, Isoprostanes, NOx
Maximal walking distance	after 30 days of (dark or milk) chocolate ingestion
Ankle Brachial Index (ABI)	after 30 days of (dark or milk) chocolate ingestion

Trial Locations

Locations (1)

Sapienza University of Rome, I Clinica Medica, Research Tower; 🇮🇹 Rome, Italy