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