Pioglitazone Treatment for Hyperglycemic Acute Ischemic Stroke

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

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.

Study Overview

• Status: Terminated
• Conditions: Hyperglycemia; Diabetes; Stroke, Acute
• Intervention / Treatment: Drug: Pioglitazone 45 mg; Drug: Placebo oral tablet

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.

• Study Type: Interventional
• Enrollment (Actual): 1
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Hershey, Pennsylvania, United States, 17033
      • Penn State College of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Pioglitazone treatment group; oral administration of 45mg Pioglitazone daily for three subsequent days, initiated within 12h of stroke symptom onset	Drug: Pioglitazone 45 mg; 45mg Pioglitazone daily for three subsequent days, initiated within 12h of stroke symptom onset
PLACEBO_COMPARATOR: Placebo group; Oral administration of placebo daily for three subsequent days, initiated within 12h of stroke symptom onset	Drug: Placebo oral tablet; placebo daily for three subsequent days, initiated within 12h of stroke symptom onset

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Milton S. Hershey Medical Center

Study record dates

Study Major Dates

• Study Start (ACTUAL): September 1, 2020
• Primary Completion (ACTUAL): April 7, 2021
• Study Completion (ACTUAL): April 7, 2021

Study Registration Dates

• First Submitted: October 8, 2019
• First Submitted That Met QC Criteria: October 9, 2019
• First Posted (ACTUAL): October 10, 2019

Study Record Updates

• Last Update Posted (ACTUAL): September 15, 2022
• Last Update Submitted That Met QC Criteria: August 23, 2022
• Last Verified: August 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Glucose Metabolism Disorders; Metabolic Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Hyperglycemia; Stroke; Ischemic Stroke; Hypoglycemic Agents; Physiological Effects of Drugs; Pioglitazone
• Other Study ID Numbers: 00011042

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes