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Measurement of Platelet Dense Granule Release in Healthy Volunteers

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00942617
Recruitment Status : Withdrawn (funding issue)
First Posted : July 21, 2009
Last Update Posted : December 7, 2015
Information provided by (Responsible Party):
John Oates, Vanderbilt University

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.

Condition or disease Intervention/treatment Phase
Platelet Aggregation Drug: Aspirin Not Applicable

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 0 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
Official Title: Measurement of Platelet Dense Granule Release in Healthy Volunteers
Study Start Date : July 2009
Actual Primary Completion Date : June 2012
Actual Study Completion Date : June 2012

Resource links provided by the National Library of Medicine

Drug Information available for: Aspirin

Arm Intervention/treatment
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

Primary Outcome Measures :
  1. 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 ]

Secondary Outcome Measures :
  1. 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 ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00942617

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United States, Tennessee
Vanderbilt University
Nashville, Tennessee, United States, 37232
Sponsors and Collaborators
Vanderbilt University
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Principal Investigator: John A Oates, M.D. Vanderbilt University
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Responsible Party: John Oates, Professor of Medicine and Pharmacology, Vanderbilt University Identifier: NCT00942617    
Other Study ID Numbers: IRB# 080895
NIH/NHLBI #81009
First Posted: July 21, 2009    Key Record Dates
Last Update Posted: December 7, 2015
Last Verified: December 2015
Keywords provided by John Oates, Vanderbilt University:
platelet aggregation
granule secretion
thromboxane production
ATP release
aspirin resistance
platelet activation
flow cytometry
Platelet aggregation in healthy volunteers
Additional relevant MeSH terms:
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Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Inflammatory Agents
Antirheumatic Agents
Fibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action
Platelet Aggregation Inhibitors
Cyclooxygenase Inhibitors
Enzyme Inhibitors