Safety of Pioglitazone for Hematoma Resolution In Intracerebral Hemorrhage - Full Text View

Sponsor:	The University of Texas Health Science Center, Houston
Information provided by:	The University of Texas Health Science Center, Houston
ClinicalTrials.gov Identifier:	NCT00827892

Purpose

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.

Condition	Intervention	Phase
Intracerebral Hemorrhage	Drug: Pioglitazone Drug: Placebo Control	Phase II

Study Type:	Interventional
Study Design:	Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Placebo Control, Parallel Assignment, Safety Study
Official Title:	Safety of Pioglitazone for Hematoma Resolution In Intracerebral Hemorrhage

Resource links provided by NLM:

Drug Information available for: Pioglitazone Pioglitazone hydrochloride

U.S. FDA Resources

Further study details as provided by The University of Texas Health Science Center, Houston:

Primary Outcome Measures:

The primary measure of safety will be mortality at discharge. [ Time Frame: At hospital discharge or Day 14, whichever occurs first. ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

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. [ Time Frame: 3 months, 6 months, and during hospitalization ] [ Designated as safety issue: Yes ]

Estimated Enrollment:	80
Study Start Date:	March 2009
Estimated Study Completion Date:	September 2012
Estimated Primary Completion Date:	March 2012 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1: Experimental	Drug: Pioglitazone Escalating doses for 3 days, then 30 mg orally daily for the duration of the study as determined by MRI
2: Placebo Comparator	Drug: Placebo Control Lactose Capsule administered by mouth daily for the duration of the study as determined by MRI

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 (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.

Eligibility

Ages Eligible for Study:	18 Years to 80 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

age 18-80 years
clinical presentation of spontaneous ICH
CT scan compatible with spontaneous ICH
Time to PIO treatment ≤ 24 hours from symptom onset
GCS ≥ 6 on initial presentation OR improvement to a GCS ≥ 6 within the time frame for enrollment
Hematoma volume ≥ 5cc on initial head CT.

Exclusion Criteria:

Participation in another investigational trial in the previous 30 days
Patient will undergo surgical evacuation of ICH (ventriculostomy does NOT exclude patient)
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.
GCS < 6
Baseline mRS ≥ 3
Primary intraventricular hemorrhage
ICH due to coagulopathy (PT > 15 sec or INR > 1.3, PTT > 36) or trauma
History of intolerance or allergy to any TZD
Thrombocytopenia: platelet count < 100,000
Clinically significant hepatic disease as demonstrated by history, clinical exam (ascites, varices), or laboratory findings (LFTs ≥ 2x normal, coagulopathy as described above)
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
Pregnancy as determined by a urine pregnancy test
Severe anemia at presentation: hemoglobin < 10 g/dL or hematocrit < 30%
Malignancy (history of or active)
Patient unlikely, in the investigator's opinion, to complete the study and return for follow-up visits for any reason

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00827892

Contacts

Contact: Nicole R Gonzales, MD	713-500-7109	Nicole.R.Gonzales@uth.tmc.edu
Contact: Indrani Acosta, MD	713-500-7091	Indrani.Acosta@uth.tmc.edu

Locations

United States, Texas
Memorial Hermann Hospital	Recruiting
Houston, Texas, United States, 77030

Sponsors and Collaborators

The University of Texas Health Science Center, Houston

Investigators

Principal Investigator:

Nicole R Gonzales, MD

University of Texas Medical School-Houston

More Information

Additional Information:

Related Info This link exits the ClinicalTrials.gov site

Publications:

Zhao X, Sun G, Zhang J, Strong R, Song W, Gonzales N, Grotta JC, Aronowski J. Hematoma resolution as a target for intracerebral hemorrhage treatment: role for peroxisome proliferator-activated receptor gamma in microglia/macrophages. Ann Neurol. 2007 Apr;61(4):352-62.

Zhao X, Grotta J, Gonzales N, Aronowski J. Hematoma Resolution as a Therapeutic Target. The Role of Microglia/Macrophages. Stroke. 2008 Dec 8; [Epub ahead of print]

Responsible Party:	The University of Texas Health Science Center, Houston ( Nicole R. Gonzales, MD )
Study ID Numbers:	HSC-MS-08-0410, P50 NS044227-5
Study First Received:	January 21, 2009
Last Updated:	February 8, 2010
ClinicalTrials.gov Identifier:	NCT00827892 History of Changes
Health Authority:	United States: Food and Drug Administration

Keywords provided by The University of Texas Health Science Center, Houston:

Intracerebral Hemorrhage
Treatment
MRI

Additional relevant MeSH terms:

Cerebral Hemorrhage
Intracranial Hemorrhages
Hemorrhage
Pioglitazone
Physiological Effects of Drugs
Nervous System Diseases
Vascular Diseases
Central Nervous System Diseases

Brain Diseases
Cerebrovascular Disorders
Pharmacologic Actions
Hematoma
Pathologic Processes
Hypoglycemic Agents
Cardiovascular Diseases

ClinicalTrials.gov processed this record on February 08, 2010