Diabetes, Healthy, Platelet Function
Conditions
Keywords
Pioglitazone, Thiazolidinediones, Platelet Function, Platelet aggregation, Diabetic, Aspirin.
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.
Detailed description
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.
Interventions
DRUGAspirin
81 mg
DRUGPioglitazone
30mg Pioglitazone x1
Sponsors
University of Rochester
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
21 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* 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.
Exclusion criteria
* 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent Platelet Aggregation Induced by Arachidonic Acid | at baseline and days 6-9 | 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. |
| Percent Platelet Aggregation Induced by Collagen | baseline and day 6-9 | 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Pioglitazone With or Without 81mg Aspirin 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. | 40 |
| Total | 40 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Withdrawal by Subject | 2 |
Baseline characteristics
| Characteristic | Pioglitazone With or Without 81mg Aspirin |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 6 Participants |
| Age, Categorical Between 18 and 65 years | 34 Participants |
| Age, Continuous | 49 years STANDARD_DEVIATION 32 |
| Region of Enrollment United States | 40 participants |
| Sex: Female, Male Female | 23 Participants |
| Sex: Female, Male Male | 17 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 0 / 40 |
| serious Total, serious adverse events | 0 / 40 |
Outcome results
Primary
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.
Time frame: at baseline and days 6-9
Population: Analysis population determined per protocol.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pioglitazone With or Without 81mg Aspirin | Percent Platelet Aggregation Induced by Arachidonic Acid | Sample 1 | 80 maximum percentage aggregation | Standard Deviation 5 |
| Pioglitazone With or Without 81mg Aspirin | Percent Platelet Aggregation Induced by Arachidonic Acid | Sample 2 | 90 maximum percentage aggregation | Standard Deviation 3 |
| Pioglitazone With or Without 81mg Aspirin | Percent Platelet Aggregation Induced by Arachidonic Acid | Sample 3 | 60 maximum percentage aggregation | Standard Deviation 6 |
| Pioglitazone With or Without 81mg Aspirin | Percent Platelet Aggregation Induced by Arachidonic Acid | Sample 4 | 29 maximum percentage aggregation | Standard Deviation 6 |
Primary
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.
Time frame: baseline and day 6-9
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pioglitazone With or Without 81mg Aspirin | Percent Platelet Aggregation Induced by Collagen | Sample 1 | 89 maximum percentage aggregation | Standard Deviation 3 |
| Pioglitazone With or Without 81mg Aspirin | Percent Platelet Aggregation Induced by Collagen | Sample 2 | 93 maximum percentage aggregation | Standard Deviation 2 |
| Pioglitazone With or Without 81mg Aspirin | Percent Platelet Aggregation Induced by Collagen | Sample 3 | 83 maximum percentage aggregation | Standard Deviation 3 |
| Pioglitazone With or Without 81mg Aspirin | Percent Platelet Aggregation Induced by Collagen | Sample 4 | 78 maximum percentage aggregation | Standard Deviation 3 |