Pioglitazone Treatment for Hyperglycemic Acute Ischemic Stroke

Study Overview
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Brief Summary
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Study objective is to determine whether Pioglitazone (PGZ) can improve clinical outcomes in hyperglycemic acute ischemic stroke (IS). The rationale for the proposed research is to develop an acute intervention that can improve neurological recovery and decrease mortality and morbidity in high-risk diabetic stroke patients.

Detailed Description
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This is a prospective, randomized, double blinded stroke intervention study. Patients presenting with hyperglycemia (blood glucose level = or > than 150mg/dl) and acute stroke symptoms within 12h of onset will be randomized to either treatment with PGZ or placebo. Patients will receive oral drug vs placebo once daily for three consecutive days. Blood samples will be obtained at baseline and during the subsequent three days to collect various biomarkers of the stress-immune response following ischemic stroke. Clinical outcomes (NIH-SS and mRS) will be determined at 3 months. Secondary outcome measures are changes in the various blood biomarkers comparing both study groups.

Official Title
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Pioglitazone Treatment for Hyperglycemic Acute Ischemic Stroke: Effects on the Stress-Immune Response

Conditions
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Diabetes, Stroke, Acute, Hyperglycemia

Intervention / Treatment
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* Drug: Pioglitazone 45 mg
* Drug: Placebo oral tablet


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Stroke Patients ages 21 and over Blood sugar ≥ 150 mg/dl Study drug treatment should be initiated within 12 hours after time of symptom onset, if known, or the time last known normal (if time to symptom onset is unknown) MRI or CT proven ischemic stroke Initial NIH SS of ≥ 2 Willing and able to provide consent Exclusion Criteria: Known hypersensitivity to PGZ. Infection at the time of presentation as defined by body temperature > 38 degrees C , pneumonia evident on chest X-ray, urinary tract infection (positive tests for nitrites, leukocyte esterase, and bacteria on urine analysis), other acute infection per history or current use of antibiotic or antiviral treatment. Active malignancy and / or autoimmune disease requiring treatment. Use of immunomodulatory drugs or chemotherapy. History of stroke or brain injury within the last 90 days prior to presentation. Acute illness within the last 30 days which could have affected the white blood cell count. Known history of clinically significant hypoglycemia. Patients already taking PGZ. Active liver disease (ALT and /or AST 2.5 times the upper limit of normal, total bilirubin > 1.2 mg/dl). Acute decompensated heart failure, and/or admission for an acute coronary syndrome, myocardial infarction (MI), cardiac arrest, coronary artery surgery within the past 3 months and patients with New York Heart association Class III and IV heart failure. History of bladder cancer Pregnant and nursing women. Currently incarcerated patients.

Ages Eligible for Study
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Minimum Age: 21 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Pioglitazone treatment group<br>oral administration of 45mg Pioglitazone daily for three subsequent days, initiated within 12h of stroke symptom onset | Drug: Pioglitazone 45 mg<br>* 45mg Pioglitazone daily for three subsequent days, initiated within 12h of stroke symptom onset<br>|
| Placebo Comparator: Placebo group<br>Oral administration of placebo daily for three subsequent days, initiated within 12h of stroke symptom onset | Drug: Placebo oral tablet<br>* placebo daily for three subsequent days, initiated within 12h of stroke symptom onset<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Neurological Status | NIH-Stroke scale (0-42) to assess neurological function with 0 being no deficits and 42 being the worst score | 90 days post stroke | 
| Degree of Disability or Dependence in the Daily Activities | Measured using the modified Rankin Scale (0-6) to assess neurological function with a score of 0 for no neurological deficits and a maximum of 6 for an expired patient | 90 days post stroke | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Concentration of Markers of Neutrophil Activation and Function | measured in blood by flow cytometry | 24 hours, 48 hours, and 90 days post-stroke | 
| Concentration of Stress Response Markers Including Cortisol, Norepinephrine and Epinephrine | measured in blood | 24 hours, 48 hours, and 90 days poststroke |