Measurement of Platelet Dense Granule Release in Healthy Volunteers

Platelet Aggregation Clinical Trial

Official title:

Measurement of Platelet Dense Granule Release in Healthy Volunteers

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT00942617
• Other study ID #: IRB# 080895
• Secondary ID: NIH/NHLBI #81009
• Status: Withdrawn
• Phase: N/A
• First received: July 17, 2009
• Last updated: December 4, 2015
• Start date: July 2009
• Est. completion date: June 2012

Study information

• Verified date: December 2015
• Source: Vanderbilt University
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: June 2012
• Est. primary completion date: June 2012
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 18 Years and older

Eligibility

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.

Study Design

Endpoint Classification: Pharmacodynamics Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Basic Science

Related Conditions & MeSH terms

• Platelet Aggregation

Intervention

Drug:
• Aspirin
40 mg non-enteric coated ASA once daily for 21 + or - 2 days

Locations

Country	Name	City	State
United States	Vanderbilt University	Nashville	Tennessee

Sponsors (1)

Lead Sponsor	Collaborator
Vanderbilt University

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The primary measurement will be platelet 5-HT release induced by ADP after 1 and 2 weeks administration of daily ASA.		3 weeks	No
Secondary	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.		3 weeks	No