Measurement of Platelet Dense Granule Release in Healthy Volunteers
Recruitment status was Active, not recruiting
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Purpose
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.
| Condition | Intervention |
|---|---|
|
Platelet Aggregation |
Drug: Aspirin |
| Study Type: | Interventional |
| Study Design: | Endpoint Classification: Pharmacodynamics Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Basic Science |
| Official Title: | Measurement of Platelet Dense Granule Release in Healthy Volunteers |
- The primary measurement will be platelet 5-HT release induced by ADP after 1 and 2 weeks administration of daily ASA. [ Time Frame: 3 weeks ] [ Designated as safety issue: No ]
- 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. [ Time Frame: 3 weeks ] [ Designated as safety issue: No ]
| Estimated Enrollment: | 20 |
| Study Start Date: | July 2009 |
| Estimated Study Completion Date: | February 2011 |
| Estimated Primary Completion Date: | February 2011 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Experimental: 40 mg non-enteric coated aspirin
40 mg non-enteric coated ASA once daily for 21 + or - 2 days
|
Drug: Aspirin
40 mg non-enteric coated ASA once daily for 21 + or - 2 days
|
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| Ages Eligible for Study: | 18 Years and older |
| Genders Eligible for Study: | Male |
| Accepts Healthy Volunteers: | Yes |
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.
Contacts and Locations| United States, Tennessee | |
| Vanderbilt University | |
| Nashville, Tennessee, United States, 37232 | |
| Principal Investigator: | John A Oates, M.D. | Vanderbilt University |
More Information
No publications provided
| Responsible Party: | John A. Oates, M.D., Vanderbilt University |
| ClinicalTrials.gov Identifier: | NCT00942617 History of Changes |
| Other Study ID Numbers: | IRB# 080895, NIH/NHLBI #81009 |
| Study First Received: | July 17, 2009 |
| Last Updated: | February 23, 2010 |
| Health Authority: | United States: Institutional Review Board |
Keywords provided by Vanderbilt University:
|
platelet aggregation granule secretion thromboxane production cyclooxygenase-1 ATP release |
aspirin resistance platelet activation flow cytometry Platelet aggregation in healthy volunteers |
Additional relevant MeSH terms:
|
Aspirin Anti-Inflammatory Agents, Non-Steroidal Analgesics, Non-Narcotic Analgesics Sensory System Agents Peripheral Nervous System Agents Physiological Effects of Drugs Pharmacologic Actions Anti-Inflammatory Agents Therapeutic Uses Antirheumatic Agents |
Fibrinolytic Agents Fibrin Modulating Agents Molecular Mechanisms of Pharmacological Action Cardiovascular Agents Hematologic Agents Platelet Aggregation Inhibitors Cyclooxygenase Inhibitors Enzyme Inhibitors Antipyretics Central Nervous System Agents |
ClinicalTrials.gov processed this record on May 16, 2013