Stroke, Acute, Hyperglycemia, Diabetes
Conditions
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.
Interventions
45mg Pioglitazone daily for three subsequent days, initiated within 12h of stroke symptom onset
DRUGPlacebo oral tablet
placebo daily for three subsequent days, initiated within 12h of stroke symptom onset
Sponsors
Milton S. Hershey Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
21 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Neurological Status | 90 days post stroke | NIH-Stroke scale (0-42) to assess neurological function with 0 being no deficits and 42 being the worst score |
| Degree of Disability or Dependence in the Daily Activities | 90 days post stroke | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Concentration of Markers of Neutrophil Activation and Function | 24 hours, 48 hours, and 90 days post-stroke | measured in blood by flow cytometry |
| Concentration of Stress Response Markers Including Cortisol, Norepinephrine and Epinephrine | 24 hours, 48 hours, and 90 days poststroke | measured in blood |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Pioglitazone Treatment Group oral administration of 45mg Pioglitazone daily for three subsequent days, initiated within 12h of stroke symptom onset
Pioglitazone 45 mg: 45mg Pioglitazone daily for three subsequent days, initiated within 12h of stroke symptom onset | 0 |
| Placebo Group Oral administration of placebo daily for three subsequent days, initiated within 12h of stroke symptom onset
Placebo oral tablet: placebo daily for three subsequent days, initiated within 12h of stroke symptom onset | 1 |
| Total | 1 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 0 | 1 |
Baseline characteristics
| Characteristic | Placebo Group | Total |
|---|---|---|
| Age, Continuous | 72 years STANDARD_DEVIATION 0 | 72 years STANDARD_DEVIATION 0 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 1 Participants |
| Race (NIH/OMB) White | 0 Participants | 0 Participants |
| Region of Enrollment United States | 1 participants | 1 participants |
| Sex: Female, Male Female | 1 Participants | 1 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 0 | 0 / 1 |
| other Total, other adverse events | 0 / 0 | 0 / 1 |
| serious Total, serious adverse events | 0 / 0 | 0 / 1 |
Outcome results
Primary
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
Time frame: 90 days post stroke
Population: Subject that received Placebo was lost to follow up and 90 day outcome data was not collected.
Primary
Neurological Status
NIH-Stroke scale (0-42) to assess neurological function with 0 being no deficits and 42 being the worst score
Time frame: 90 days post stroke
Population: Subject that received Placebo was lost to follow up and 90 day outcome data was not collected.
Secondary
Concentration of Markers of Neutrophil Activation and Function
measured in blood by flow cytometry
Time frame: 24 hours, 48 hours, and 90 days post-stroke
Population: Subject that received Placebo was lost to follow up and data was not collected for any time point
Secondary
Concentration of Stress Response Markers Including Cortisol, Norepinephrine and Epinephrine
measured in blood
Time frame: 24 hours, 48 hours, and 90 days poststroke
Population: Subject that received Placebo was lost to follow up and data was not collected for any time point.