Clinical trial NCT02630862: Oxidative Stress and Oxysterols Profiling in Patients With Carotid Revascularization
Official title: Oxidative Stress and Oxysterols Profiling in Patients With Carotid Revascularization: Effect of Antithrombotic Treatment
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Carotid Stenosis
Cardiovascular Disease
Atherosclerosis
Stroke
Keywords: oxidative stress
atherosclerosis
carotid stenosis
oxysterols
vitamin E
lipid peroxidation
antioxidants
aspirin
dipyridamole
Lead sponsor: University of Roma La Sapienza
Sponsor class: OTHER
Collaborators: name: Civic Hospital, Italy
First posted: 2015-12-15
Enrollment: 240
Sex: ALL
Minimum age (years): 50
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL

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.

Eligibility criteria: 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

Primary outcomes:
measure: Level of oxysterol measured by isotope dilution gas chromatography-mass spectrometry
timeFrame: 6-months
measure: Level of alpha- and gamma-tocopherol (vitamin E isomers) by isotope dilution gas chromatography-mass spectrometry
timeFrame: 6-months
Secondary outcomes:
Other outcomes:
Locations:
city: Latina
country: Italy
facility: Civic Hospital, Vascular Surgery Unit
state: LT
Study officials:
affiliation: Goretti Hospital, Latina
name: Giovanni Bertoletti, M.D.
role: PRINCIPAL_INVESTIGATOR
References: