Clinical trial NCT00942617: Measurement of Platelet Dense Granule Release in Healthy Volunteers
Official title: Measurement of Platelet Dense Granule Release in Healthy Volunteers
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: NA
Conditions: Platelet Aggregation
Keywords: platelet aggregation
granule secretion
thromboxane production
cyclooxygenase-1
ATP release
aspirin resistance
platelet activation
flow cytometry
Platelet aggregation in healthy volunteers
Lead sponsor: Vanderbilt University
Sponsor class: OTHER
First posted: 2009-07-21
Enrollment: 0
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: BASIC_SCIENCE

Brief summary: Aspirin has been shown to reduce cardiovascular events in at risk individuals. Elucidation of mechanisms of aspirin resistance and a possible loss of effect of aspirin over time with chronic aspirin treatment necessitate a more precise method of measuring the "release phase" of platelet activation, including the release of dense granules from platelets.

Detailed description: This is a proposal for a pilot study to evaluate the feasibility of measuring 5-hydroxytryptamine (5-HT) release from platelets as an indicator of dense granule release during platelet activation in volunteers taking aspirin.

One phase of platelet response to activating agonists involves release of dense granules, which are known to contain 5HT (serotonin) and ATP. There are various methods of measuring the degranulation of platelets: ATP release can be measured using a lumiaggregometer, and release of 14C radiolabeled 5-HT from platelets. Using the aggregometer and a 14C labeled 5-HT assay can be used to measure 5-HT release from platelets.

Our experience suggests that ADP-induced ATP release is insensitive to detect very low levels of platelet dense granule release, which occurs in aspirin-treated subjects. The pilot study will permit optimizing the method for reliably detecting low levels of 5HT release in patients who achieve submaximal inhibition of the cyclooxygenase during aspirin treatment.

Eligibility criteria: Inclusion Criteria:

* Males over age 18
* Non-smokers
* No chronic medical illness
* No chronic medications

Exclusion Criteria:

* ASA/NSAID use previous 14 days.
* History of chronic NSAID use.
* Currently taking NSAIDs, opioid analgesics, corticosteroids, or anticoagulants.
* History of coronary artery disease, myocardial infarction, coronary artery bypass grafting, percutaneous angioplasty, diabetes mellitus or stroke.
* History of hypertension
* BMI \>35
* Smokers
* History of gastric, duodenal, or esophageal ulcers or serious gastrointestinal bleed.
* History of frequent headaches, pain syndrome, or other condition requiring frequent use of analgesics.
* History of adverse reaction to ASA.
* Initial platelet count \<100K/µl or \>500K/µl.
* Initial hematocrit \<35% or \>50%.
* Weight less than 110 pounds.

Female subjects will be excluded to avoid possible confounding uterine smooth muscle production of prostaglandins which various throughout the menstrual cycle.

Primary outcomes:
measure: The primary measurement will be platelet 5-HT release induced by ADP after 1 and 2 weeks administration of daily ASA.
timeFrame: 3 weeks
Secondary outcomes:
measure: Measurements will include platelet COX-1 activity, flow cytometric measurement of markers of platelet activation, platelet aggregation and ATP release, and serum thromboxane B2 (TxB2) levels, at each timepoint.
timeFrame: 3 weeks
Other outcomes:
Locations:
city: Nashville
country: United States
facility: Vanderbilt University
state: Tennessee
Study officials:
affiliation: Vanderbilt University
name: John A Oates, M.D.
role: PRINCIPAL_INVESTIGATOR
References: