Oxidative Stress and Oxysterols Profiling in Patients With Carotid Revascularization

Not Applicable

Completed

• Conditions: Cardiovascular Disease; Stroke; Carotid Stenosis; Atherosclerosis
• Interventions: Drug: Aspirin; Drug: aspirin plus dipyridamole

• Registration Number: NCT02630862
• Lead Sponsor: University of Roma La Sapienza

Brief Summary

The combination of aspirin and dipyridamole, two antiplatelet drugs, is approved in Italy for the secondary prevention of cerebral embolism in patients with carotid atherosclerosis.

Besides antiplatelet activity, Dipyridamole has additional pharmacological action, including vasodilation and antioxidant properties.

A role for oxidative stress has been suggested in acute cerebrovascular disease. In this study the investigators want to test the in vivo antioxidant activity of dipyridamole in patients who are candidate to take the drug under approved conditions of the Italian Drug Regulation Agency, i.e. secondary prevention of TIA/Stroke in patinets with carotid stenosis (\>= 70%).

To test the hypothesis that dipyridamole acts as antioxidant in vivo, oxysterols (products of cholesterol autoxidation) and vitamin E are measured in plasma before and after 6 months therapy after carotid endoarterectomy. Since dipyridamole is approved as combination preparation with aspirin, a control group of patients taking aspirin alone is enrolled.

Outcome measures: plasma biomarkers (oxysterols and vitamin E) change at two time points: baseline and 6-months therapy.

Detailed Description

Dipyridamole has been shown to act as potent antioxidant in vitro. The aim of the present study is to analyze if dipyridamole retains the antioxidant in vivo in man.

The investigators identified a clinical setting where dipyridamole is approved for clinical use, i.e. secondary prevention of stroke, to test the hypothesis that dipyridamole given orally could affect circulating markers of oxidative stress, in particular reduction in oxysterols (autoxidation products of cholesterol) and increase in vitamin E concentration.

Methods. Two arms are included in the study: a) dipyridamole plus aspirin (in Italy the use of dipyridamole is approved in combination with aspirin); b) aspirin alone as comparison arm. Patients eligible for endoarterectomy for the presence of carotid stenosis \>= 70% are randomized in the two arms. The study is open labeled for the patient and clinical investigators who have in charge the patinets . The study is blinded for the technicians performing biomarker assessment and investigators responsible for data analysis.

Blood is taken at baseline (before surgery) and after six months of treatment. Oxysterol profiling and vitamin E are measured by isotope dilution gas chromatography and mass spectrometry.

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study Start: 2010-09
• Primary Completion: 2014-06
• Study Completion: 2014-12
• Study First Submitted: 2015-05-26
• Status Verified: 2015-12
• Study First Submitted QC: 2015-12-10
• Last Update Submitted: 2015-12-10
• Study First Posted: 2015-12-15
• Last Update Posted: 2015-12-15

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 240

Inclusion Criteria

• Patients with carotid atherosclerosis eligible for carotid endoarterectomy (stenosis >= 70%) with previous TIA or Stroke

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Exclusion Criteria

• Congestive heart failure, chronic liver disease, chronic kidney disease (GFR < 60%), cancer, use of antioxidant supplements in the previous 3 months, autoimmune diseases

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
aspirin	Aspirin	acetylsalcylic acid 100 mg per day give orally for six months, starting the day of carotid endoartherectomy
aspirin plus dipyridamole	aspirin plus dipyridamole	acetylsalicylic acid 25 mg plus dipyridamole extended release 200 mg, combined in a capsule, per day starting the day of carotid endoartherectomy

Primary Outcome Measures

Name	Time	Method
Level of oxysterol measured by isotope dilution gas chromatography-mass spectrometry	6-months	Oxysterols are used here as markers of oxidative stress, i.e. increased oxidative stress is refected by increased oxysterols levels
Level of alpha- and gamma-tocopherol (vitamin E isomers) by isotope dilution gas chromatography-mass spectrometry	6-months	Increased oxidative stress is expected to reduce the levels of of vitamin E isomers by consumption

Trial Locations

Locations (1)

Civic Hospital, Vascular Surgery Unit; 🇮🇹 Latina, LT, Italy