Chlorthalidone and HCTZ Impacts on Platelet Activation

Study Overview
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Brief Summary
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This will be a randomized, double-blinded, three-period crossover study of platelet activation and aggregation in 30 non-smoking healthy volunteers comparing chlorthalidone (CTD), hydrochlorothiazide (HCTZ), and aspirin (ASA; active control). The study hypothesis is that CTD has different effects on platelet activation and aggregation than HCTZ.

Official Title
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Evaluation of Platelet Effects of Chlorthalidone and Hydrochlorothiazide

Conditions
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Hypertension

Intervention / Treatment
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* Drug: Chlorthalidone 12.5 mg
* Drug: Hydrochlorothiazide 25 mg
* Drug: Aspirin 81 mg


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Men or women age 19 or older Not currently taking any routinely scheduled prescription or over the counter medications or herbal supplements No use of aspirin, clopidogrel, prasugrel, ticagrelor, cilostazol, dipyridamole, NSAID medications, or herbal supplements within the previous 7 days and able to refrain from use during the study period Systolic blood pressure > 110 mmHg and diastolic blood pressure > 60 mmHg Non-smoker Exclusion Criteria: Previous adverse reaction or allergy to HCTZ, CTD, or ASA Severe sulfonamide hypersensitivity (anaphylaxis or Stevens-Johnson syndrome) Diagnosis of any chronic disease or condition History of gout or hyperuricemia History of pancreatitis History of systemic lupus erythematosus (SLE) History of hypokalemia requiring treatment Pregnant or planning to become pregnant during the study period Breastfeeding History of hypotension History of gastrointestinal bleeding

Ages Eligible for Study
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Minimum Age: 19 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Chlorthalidone 12.5 mg<br>Chlorthalidone 12.5 mg by mouth once daily for 2 weeks | Drug: Chlorthalidone 12.5 mg<br> <br> |
| Experimental: Hydrochlorothiazide 25 mg<br>Hydrochlorothiazide 25 mg by mouth once daily for 2 weeks | Drug: Hydrochlorothiazide 25 mg<br> <br> |
| Active Comparator: Aspirin 81 mg<br>Aspirin 81 mg by mouth once daily for 2 weeks | Drug: Aspirin 81 mg<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in mean fluorescence intensity of PAC-1 | The primary endpoint for this study will be the change in mean fluorescence intensity (MFI) of the platelet activation marker PAC-1 due to HCTZ, CTD, and aspirin. | 2 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in CD62P expression | Change in platelet expression of CD62P (p-selectin) in response to CTD, HCTZ, and ASA. | 2 weeks | 
| Change in platelet aggregation | Change in platelet aggregation measured by flow cytometry in response to CTD, HCTZ, and ASA | 2 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hypertension, Platelet activation, Platelet aggregation, Chlorthalidone