Clinical trial NCT04123067: Pioglitazone Treatment for Hyperglycemic Acute Ischemic Stroke
Official title: Pioglitazone Treatment for Hyperglycemic Acute Ischemic Stroke: Effects on the Stress-Immune Response
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: Stroke, Acute
Hyperglycemia
Diabetes
Lead sponsor: Milton S. Hershey Medical Center
Sponsor class: OTHER
First posted: 2019-10-10
Enrollment: 1
Sex: ALL
Minimum age (years): 21
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: Inclusion Criteria:

1. Stroke Patients ages 21 and over
2. Blood sugar ≥ 150 mg/dl
3. 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)
4. MRI or CT proven ischemic stroke
5. Initial NIH SS of ≥ 2
6. Willing and able to provide consent

Exclusion Criteria:

1. Known hypersensitivity to PGZ.
2. 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.
3. Active malignancy and / or autoimmune disease requiring treatment.
4. Use of immunomodulatory drugs or chemotherapy.
5. History of stroke or brain injury within the last 90 days prior to presentation.
6. Acute illness within the last 30 days which could have affected the white blood cell count.
7. Known history of clinically significant hypoglycemia.
8. Patients already taking PGZ.
9. Active liver disease (ALT and /or AST 2.5 times the upper limit of normal, total bilirubin \> 1.2 mg/dl).
10. 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.
11. History of bladder cancer
12. Pregnant and nursing women.
13. Currently incarcerated patients.

Primary outcomes:
measure: Neurological Status
timeFrame: 90 days post stroke
measure: Degree of Disability or Dependence in the Daily Activities
timeFrame: 90 days post stroke
Secondary outcomes:
measure: Concentration of Markers of Neutrophil Activation and Function
timeFrame: 24 hours, 48 hours, and 90 days post-stroke
measure: Concentration of Stress Response Markers Including Cortisol, Norepinephrine and Epinephrine
timeFrame: 24 hours, 48 hours, and 90 days poststroke
Other outcomes:
Locations:
city: Hershey
country: United States
facility: Penn State College of Medicine
state: Pennsylvania
Study officials:
affiliation: Penn State College of Medicine
name: Kerstin Bettermann, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: