Effects of Pioglitazone on Platelet Function

NCT00861341 | Completed Phase 2 Results DMC

• 1 other identifier: 24695
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to determine how pioglitazone and aspirin affect platelets in the blood of diabetic and non-diabetic subjects. Platelets are small cells in the blood that help with blood clotting. Pioglitazone is a drug that is used to lower blood sugar and fats by helping the body to use insulin correctly. Pioglitazone is presently used to treat diabetes but has not been approved for non-diabetics. This study will determine whether pioglitazone reduces the activity of platelets in people who are or are not also taking aspirin.

Conditions

Diabetes; Platelet Function; Healthy

Keywords

Pioglitazone; Thiazolidinediones; Platelet Function; Platelet aggregation; Diabetic; Aspirin.

Outcome Measures

Primary Outcomes (2)

• Percent Platelet Aggregation Induced by Arachidonic Acid

  Platelet aggregation was performed by the turbidimetric method of Born with simultaneous measurement of ATP release using a Chrono-log Lumi-Aggregometer with AGGRO/LINK for Windows Software version 5.1.6. Platelet rich plasma was placed in a silicone-coated cuvette with constant stirring at 1200 rpm using a siliconized stir bar for measurement of aggregation and ATP release. Aggregation was initiated using arachidonic acid (0.5 mM). At each time point the results are shown for maximum percent aggregation with arachidonic acid for all subjects. Sample 1 was obtained at baseline (BL). Sample 2 was drawn on the same day after ingestion of a single dose of 30 mg of pioglitazone. Sample 3 was obtained 6-9 days later after the subject had ingested a single 81 mg dose of aspirin (ASA), and sample 4 was drawn later that day after ingestion of 30 mg of pioglitazone.

  at baseline and days 6-9

• Percent Platelet Aggregation Induced by Collagen

  Platelet aggregation was performed by the turbidimetric method of Born with simultaneous measurement of ATP release using a Chrono-log Lumi-Aggregometer with AGGRO/LINK for Windows Software version 5.1.6. Platelet rich plasma was placed in a silicone-coated cuvette with constant stirring at 1200 rpm using a siliconized stir bar for measurement of aggregation and ATP release. Aggregation was initiated using collagen (2ug.mL). At each time point the results are shown for maximum percent aggregation with collagen for all subjects. Sample 1 was obtained at baseline (BL). Sample 2 was drawn on the same day after ingestion of a single dose of 30 mg of pioglitazone. Sample 3 was obtained 6-9 days later after the subject had ingested a single 81 mg dose of aspirin (ASA), and sample 4 was drawn later that day after ingestion of 30 mg of pioglitazone.

  baseline and day 6-9

Study Arms (1)

Pioglitazone with or without Aspirin

EXPERIMENTAL

Blood samples will be taken at time 0 to measure platelet aggregation. 30mg Pioglitazone will be ingested and another blood sample will be obtained 90-180 minutes later for platelet aggregation. After 6-9 days, subjects will ingest 81mg of aspirin. Another blood sample will be obtained 2-24 hours later for baseline determination of platelet aggregation and activation after taking aspirin. Subjects will then ingest 30mg pioglitazone and a final blood sample will be obtained 90-180 minutes later to measure platelet aggregation.

Drug: Aspirin; Drug: Pioglitazone

Interventions

Aspirin DRUG

81 mg

Pioglitazone with or without Aspirin

Pioglitazone DRUG

30mg Pioglitazone x1

Also known as: Actos

Pioglitazone with or without Aspirin

Eligibility Criteria

• Age: 21 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects must be over 21 years of age and provide written informed consent.
• Normal subjects must have a BMI \<30 and must not have known cardiovascular disease, Diabetes Mellitus (DM), hyperlipidemia, or hypertension. Diabetic subjects must have previously diagnosed DM.

You may not qualify if:

• Subjects will be excluded if they have hypersensitivity to aspirin or pioglitazone, or if they are receiving warfarin or heparin therapy, are pregnant, or have congestive heart failure or hepatic function impairment.
• Subjects must not have taken aspirin or other drugs inhibiting platelet function such as Plavix or non-steroidal anti-inflammatory drugs for 7 days.
• Subjects will be excluded if they have a history of renal failure, severe liver disease, myeloproliferative disease or other conditions that impair platelet function.

Sponsors & Collaborators

• University of Rochester: lead

Study Sites (1)

University of Rochester

Rochester, New York, 14642, United States

Location

Related Publications (1)

• Mongan J, Mieszczanska HZ, Smith BH, Messing SP, Phipps RP, Francis CW. Pioglitazone inhibits platelet function and potentiates the effects of aspirin: a prospective observation study. Thromb Res. 2012 Jun;129(6):760-4. doi: 10.1016/j.thromres.2011.12.019. Epub 2012 Jan 4.

  PMID: 22225857 DERIVED

MeSH Terms

Conditions

Diabetes Mellitus

Interventions

Aspirin; Pioglitazone

Condition Hierarchy (Ancestors)

Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Salicylates; Hydroxybenzoates; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Thiazolidinediones; Thiazoles; Sulfur Compounds; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Charles Francis, MD
• Organization: University of Rochester, Wilmot Cancer Center

Charles_Francis@urmc.rochester.edu

585-275-3761

Study Officials

• Charles W Francis, MD

  University of Rochester

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: March 9, 2009
• First Posted: March 13, 2009
• Study Start: December 1, 2008
• Primary Completion: June 1, 2010
• Study Completion: June 1, 2011
• Last Updated: February 3, 2016
• Results First Posted: February 3, 2016

Record last verified: 2015-12

Locations

US (1)