Safety of Pioglitazone for Hematoma Resolution In Intracerebral Hemorrhage
Safety of Pioglitazone for Hematoma Resolution In Intracerebral Hemorrhage
Intracerebral hemorrhage (ICH) is a devastating disease with less than 20% of survivors being
 independent at 6 months. There is currently no approved treatment for ICH which has been
 shown to improve outcomes. In an effort to develop a new treatment for ICH, this research
 focuses on a different aspect of ICH treatment which has not yet been evaluated: enhancing
 absorption of the blood clot with medication.
Intracerebral hemorrhage (ICH) remains a devastating disease and current treatment options
 lag far behind those for ischemic stroke. Current treatment efforts for ICH are targeted
 towards the primary brain injury caused by the hemorrhage and growth of the hematoma. This
 research targets the secondary injury caused by the persistence of toxic blood degradation
 products in the brain parenchyma.

 Based on preclinical work in our lab, the peroxisome proliferator activated receptor-gamma
 (PPARγ), a member of the nuclear receptor superfamily, represents a possible target for the
 treatment of ICH aimed at promoting hematoma absorption, limiting the pro-inflammatory
 response, and protecting salvageable tissue from the damage produced by the persistence of
 toxic blood degradation products.

 Our primary specific aim is to assess the safety of the PPARγ agonist, pioglitazone (PIO) in
 increasing doses for 3 days, when administered to patients with ICH within 24 hrs of symptom
 onset. Secondarily, we aim to determine the duration of treatment of PIO for hematoma/edema
 resolution in ICH. Lastly, we aim to determine whether speed of hematoma/edema resolution in
 ICH represents a radiographic biological marker of activity which can be correlated with
 clinical outcome and treatment effect of PIO. The ultimate purpose is to provide baseline
 data on an aspect of ICH which has not been previously targeted for treatment in an effort to
 develop a safe and effective treatment strategy that may be practical and applicable for both
 specialized stroke centers and community hospitals.
Inclusion Criteria:

 1. age 18-80 years

 2. clinical presentation of spontaneous ICH

 3. CT scan compatible with spontaneous ICH

 4. Time to PIO treatment ≤ 24 hours from symptom onset

 5. GCS ≥ 6 on initial presentation OR improvement to a GCS ≥ 6 within the time frame for
 enrollment

 6. Hematoma volume ≥ 5cc on initial head CT.

 Exclusion Criteria:

 1. Participation in another investigational trial in the previous 30 days

 2. Patient will undergo surgical evacuation of ICH (ventriculostomy does NOT exclude
 patient)

 3. Inability to undergo neuroimaging with MRI (e.g. pacer, recent stent, inability to lie
 flat)

 a. If patient has mild claustrophobia or agitation amenable to mild sedation (1-2mg
 lorazepam IV or 5-10mg diazepam PO), he or she may be considered for enrollment. If,
 however, the patient has severe claustrophobia or agitation, he or she should not be
 considered for enrollment.

 4. GCS < 6

 5. Baseline mRS ≥ 3

 6. Primary intraventricular hemorrhage

 7. ICH due to coagulopathy (PT > 15 sec or INR > 1.3, PTT > 36) or trauma

 8. History of intolerance or allergy to any TZD

 9. Thrombocytopenia: platelet count < 100,000

 10. Clinically significant hepatic disease as demonstrated by history, clinical exam
 (ascites, varices), or laboratory findings (LFTs ≥ 2x normal, coagulopathy as
 described above)

 11. Co-morbid conditions, which in the opinion of the investigator, are likely to
 complicate therapy including but not limited to:

 1. A history of NYHA class II, III, or IV CHF

 2. clinically significant arrhythmia

 3. end stage AIDS

 12. Pregnancy as determined by a urine pregnancy test

 13. Severe anemia at presentation: hemoglobin < 10 g/dL or hematocrit < 30%

 14. Malignancy (history of or active)

 15. Patient unlikely, in the investigator's opinion, to complete the study and return for
 follow-up visits for any reason