Safety of Pioglitazone for Hematoma Resolution In Intracerebral Hemorrhage "SHRINC"

Completed

Phase 2 Results N/A

Trial Description

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.

Detailed Description

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 (PPARĪ³), 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 PPARĪ³ 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.

Conditions

Interventions

  • Pioglitazone (Pioglitazone)Drug
    Intervention Desc: Escalating doses for 3 days, then 30 mg orally daily for the duration of the study as determined by MRI
    ARM 1: Kind: Experimental
    Label: 1
  • Placebo Control Drug
    Intervention Desc: Lactose Capsule administered by mouth daily for the duration of the study as determined by MRI
    ARM 1: Kind: Experimental
    Label: 2

Trial Design

  • Allocation: Randomized
  • Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
  • Purpose: Treatment
  • Endpoint: Safety Study
  • Intervention: Parallel Assignment

Patient Involvement

Study participants will be randomized to one of 2 treatment arms: 1) Pioglitazone in escalating doses for 3 days, then 30 mg orally daily for the duration of the study as determined by MRI or 2) Placebo capsule administered by mouth daily for the duration of the study as determined by MRI. Study participants will have assessments during hospitalization and at Days 7, 14, 21, 28, 90, and 6 months. Duration of study medication will be determined by the time it takes for 75% of the hematoma to resolve based on MRI.

Outcomes

Type Measure Time Frame Safety Issue
Primary The primary measure of safety will be mortality at discharge or 2 weeks, whichever comes first.
Secondary Secondary measures of safety will include mortality at 3 months and 6 months, symptomatic cerebral edema during hospitalization, clinically significant congestive heart failure, edema, hypoglycemia, anemia, and hepatotoxicity.
Primary The primary measure of safety will be mortality at discharge. At hospital discharge or Day 14, whichever occurs first. Yes

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