Measurement of Platelet Dense Granule Release in Healthy Volunteers

The recruitment status of this study is unknown because the information has not been verified recently.
Verified February 2010 by Vanderbilt University.
Recruitment status was  Active, not recruiting
Sponsor:
Information provided by:
Vanderbilt University
ClinicalTrials.gov Identifier:
NCT00942617
First received: July 17, 2009
Last updated: February 23, 2010
Last verified: February 2010
  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

Resource links provided by NLM:


Further study details as provided by Vanderbilt University:

Primary Outcome Measures:
  • 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 ]

Secondary Outcome Measures:
  • 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
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.

  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00942617

Locations
United States, Tennessee
Vanderbilt University
Nashville, Tennessee, United States, 37232
Sponsors and Collaborators
Vanderbilt University
Investigators
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 August 19, 2014