CES1 Crossover Trial of Clopidogrel and Ticagrelor

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.

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Key information

Conditions

Myocardial Infarction Cardiovascular Diseases Embolism and Thrombosis Heart Diseases Infarction Ischemia Myocardial Ischemia Necrosis Pathologic Processes Pathological Conditions, Signs and Symptoms Platelet Dysfunction Thrombosis Vascular Diseases

Age range

18 year–75 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 4

Primary location

Amish Research Clinic

Lancaster, Pennsylvania, 17602, United States

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

Of Amish descent
Age 18 to 75 years
Participant in the Phamacogenomics of Anti-Platelet Intervention (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
Hematocrit (Hct) < 32% or > 50%
Blood pressure > 160/95 mm Hg
Co-existing malignancy
Creatinine > 2.0 mg/dl
Aspartate transaminase (AST) or alanine transaminase (ALT) > 2 times the upper limit of normal
Thyroid-stimulating hormone (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 atrioventricular 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

Treatment and study plan

clopidogrel

Drug

Clopidogrel (75 mg/d for 8 days) will be administered. Measures of pharmacodynamics will be assessed pre- and post-drug administration.

Other names: Plavix

Ticagrelor

Drug

Ticagrelor (90 mg twice daily for 8 days) will be administered. Measures of pharmacodynamics will be assessed pre- and post-drug administration.

Other names: Brilinta

Primary outcomes

Change in Maximal Platelet Aggregation in Response to Clopidogrel

Time frame: 8 days of exposure to clopidogrel (change from baseline at day 8 reported)

Ex vivo platelet aggregometry was performed in platelet rich plasma (PRP) after stimulation with 20 μM adenosine diphosphate (ADP) at 2 time points (at baseline prior to drug administration and on the 8th day of clopidogrel [75mg/d]). Maximum platelet aggregation is recorded by the platelet aggregometer as a percentage. Data shown below represent the maximum platelet aggregation value obtained at baseline minus the maximum platelet aggregation value obtained after clopidogrel administration. Thus, values recorded below represent changes from baseline at day 8 and the unit is percent maximum aggregation. Higher reported values represent a greater reduction in platelet aggregation while lower reported values signify a smaller reduction in platelet aggregation when comparing baseline and post-clopidogrel visits.
Change in Maximal Platelet Aggregation in Response to Ticagrelor

Time frame: 8 days of independent exposure to ticagrelor (change from baseline at day 8 reported)

Ex vivo platelet aggregometry was performed in platelet rich plasma (PRP) after stimulation with 20 μM adenosine diphosphate (ADP) at 2 time points (at baseline prior to drug administration and on the 8th day of ticagrelor [90 mg twice daily]). Maximum platelet aggregation is recorded by the platelet aggregometer as a percentage. Data shown below represent the maximum platelet aggregation value obtained at baseline minus the maximum platelet aggregation value obtained after ticagrelor administration. Thus, values recorded below represent changes from baseline at day 8 and the unit is percent maximum aggregation. Higher reported values represent a greater reduction in platelet aggregation while lower reported values signify a smaller reduction in platelet aggregation when comparing baseline and post-ticagrelor visits.

Sponsors and collaborators

Lead sponsor

University of Maryland, Baltimore

Other

Registry information

Official study title

Impact of Genetic Variation in CES1 on Antiplatelet Therapy

Important dates

Study start: 2017
Primary completion: 2022
Study completion: 2022
First posted: May 22, 2017
Registry last updated: Jul 24, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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Completed