CES1 Crossover Trial of Clopidogrel and Ticagrelor
| Status: | Recruiting |
|---|---|
| Conditions: | Cardiology, Cardiology |
| Therapuetic Areas: | Cardiology / Vascular Diseases |
| Healthy: | No |
| Age Range: | 18 - 75 |
| Updated: | 2/3/2019 |
| Start Date: | August 22, 2017 |
| End Date: | October 2020 |
| Contact: | Joshua P Lewis, PhD |
| Email: | jlewis2@som.umaryland.edu |
| Phone: | 410-706-5087 |
Impact of Genetic Variation in CES1 on Antiplatelet Therapy
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.
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.
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
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