Oxidative Stress and Oxysterols Profiling in Patients With Carotid Revascularization

Stroke Clinical Trial

— ICAR  

Official title:

Oxidative Stress and Oxysterols Profiling in Patients With Carotid Revascularization: Effect of Antithrombotic Treatment

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02630862
• Other study ID #: IULIANO_Carotids
• Status: Completed
• Phase: N/A
• First received: May 26, 2015
• Last updated: December 10, 2015
• Start date: September 2010
• Est. completion date: December 2014

Study information

• Verified date: December 2015
• Source: University of Roma La Sapienza
• Contact: n/a
• Is FDA regulated: No
• Health authority: Italy: The Italian Medicines Agency
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 240
• Est. completion date: December 2014
• Est. primary completion date: June 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 50 Years to 90 Years

Eligibility

Inclusion Criteria:

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

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

Study Design

Allocation: Randomized, Endpoint Classification: Bio-equivalence Study, Intervention Model: Parallel Assignment, Masking: Single Blind (Investigator)

Related Conditions & MeSH terms

• Atherosclerosis
• Cardiovascular Disease
• Cardiovascular Diseases
• Carotid Stenosis
• Stroke

Intervention

Drug:
• Aspirin
Aspirin is a standard and guidelines supported therapy for patients undergoing carotid endoarterectomy as secondary prevention measure of cardiovascular risk
• aspirin plus dipyridamole
the combination of aspirin plus dipyridamole is approved to lower the risk of stroke in people who have had a transient ischemic attack or stroke

Locations

Country	Name	City	State
Italy	Civic Hospital, Vascular Surgery Unit	Latina	LT

Sponsors (2)

Lead Sponsor	Collaborator
University of Roma La Sapienza	Civic Hospital, Italy

Country where clinical trial is conducted

Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Level of oxysterol measured by isotope dilution gas chromatography-mass spectrometry	Oxysterols are used here as markers of oxidative stress, i.e. increased oxidative stress is refected by increased oxysterols levels	6-months	No
Primary	Level of alpha- and gamma-tocopherol (vitamin E isomers) by isotope dilution gas chromatography-mass spectrometry	Increased oxidative stress is expected to reduce the levels of of vitamin E isomers by consumption	6-months	No