CES1 Crossover Trial of Clopidogrel and Ticagrelor

• Status: Recruiting
• Trial end date: 2022-01-01
• Target enrollment: 0
• Participant gender: All

Summary

The purpose of this investigation is to evaluate when genetic variation in the carboxylesterase 1 (CES1) gene influences antiplatelet therapy response, as assessed by ex vivo platelet aggregometry, in healthy participants treated with clopidogrel and ticagrelor. We hypothesize that genetic variation in CES1 will significantly impact on-clopidogrel platelet aggregation while having a minimal effect in ticagrelor-treated subjects.

Specific Aim: To conduct a prospective randomized crossover study of clopidogrel and ticagrelor in healthy individuals stratified by CES1 genotype. Participants will be recruited by CES1 genotype into a randomized crossover study of clopidogrel (75 mg daily for 7d) and ticagrelor (90 mg twice daily for 7d) with extensive phenotyping including ex vivo platelet aggregometry performed pre- and post-drug administration in order to assess the interaction of genotype and drug choice on on-treatment platelet function.

• Phase: Phase 4
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: University of Maryland; University of Maryland, Baltimore
• Treatments: Clopidogrel; Ticagrelor; Ticlopidine

Criteria

Inclusion Criteria:

• Of Amish descent

• Age 18 to 75 years

• Participant in the PAPI-1 Study or other Amish Research Center study, or a family member of an Amish Research Center study participant.

Exclusion Criteria:

• Clopidogrel or ticagrelor allergy

• Platelet count < 100,000 mm3 or > 500,000 mm3

• Hct < 32% or > 50%

• Blood pressure > 160/95 mm Hg

• Co-existing malignancy

• Creatinine > 2.0 mg/dl

• AST or ALT > 2 times the upper limit of normal

• TSH < 0.40 or > 5.50 mU/L

• Pregnant or breast feeding

• History of gastrointestinal bleeding, a major life-threatening bleeding event, active pathological bleeding, bleeding diathesis, or coagulopathy

• History of stroke or transient ischemic attack, deep vein thrombosis, or atrial fibrillation

• History of myocardial infarction, coronary artery bypass surgery, unstable angina, or angioplasty

• History of sick sinus syndrome, 2nd or 3rd degree AV block, or bradycardia-related syncope

• Type 1 or Type 2 diabetes mellitus

• Surgery in the past 3 months or planned surgery in the next 3 months

• Participant cannot willingly and safely discontinue medications that, in the opinion of the study physician would affect the outcomes to be measured for at least 1 week prior to study initiation through completion of the study

• Participant is unwilling to discontinue taking vitamins and/or supplements that, in the opinion of the study physician would affect the outcomes to be measured for 1 week prior to the study initiation through the the completion of the study

• Any other condition that would place prospective participants at unacceptable risk or render them unable to meet the requirements of the protocol in the opinion of the site investigator