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Safety of Pioglitazone for Hematoma Resolution In Intracerebral Hemorrhage (SHRINC)

Primary Purpose

Intracerebral Hemorrhage

Status

Completed

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

Pioglitazone

Placebo Control

About this trial

This is an interventional treatment trial for Intracerebral Hemorrhage focused on measuring Intracerebral Hemorrhage, Treatment, MRI

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Memorial Hermann Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Arm Description

Outcomes

Primary Outcome Measures

The primary measure of safety will be mortality at discharge.

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.

Full Information

NCT ID

NCT00827892

First Posted

January 21, 2009

Last Updated

October 1, 2015

Sponsor

The University of Texas Health Science Center, Houston

1. Study Identification

Unique Protocol Identification Number

NCT00827892

Brief Title

Safety of Pioglitazone for Hematoma Resolution In Intracerebral Hemorrhage

Acronym

SHRINC

Official Title

Safety of Pioglitazone for Hematoma Resolution In Intracerebral Hemorrhage

Study Type

Interventional

2. Study Status

Record Verification Date

October 2015

Overall Recruitment Status

Completed

Study Start Date

March 2009 (undefined)

Primary Completion Date

April 2013 (Actual)

Study Completion Date

November 2013 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

The University of Texas Health Science Center, Houston

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

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 (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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Intracerebral Hemorrhage

Keywords

Intracerebral Hemorrhage, Treatment, MRI

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

84 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Arm Type

Experimental

Arm Title

Arm Type

Placebo Comparator

Intervention Type

Drug

Intervention Name(s)

Pioglitazone

Other Intervention Name(s)

Actos

Intervention Description

Escalating doses for 3 days, then 30 mg orally daily for the duration of the study as determined by MRI

Intervention Type

Drug

Intervention Name(s)

Placebo Control

Intervention Description

Lactose Capsule administered by mouth daily for the duration of the study as determined by MRI

Primary Outcome Measure Information:

Title

The primary measure of safety will be mortality at discharge.

Time Frame

At hospital discharge or Day 14, whichever occurs first.

Secondary Outcome Measure Information:

Title

Time Frame

3 months, 6 months, and during hospitalization

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

80 Years

Accepts Healthy Volunteers

Eligibility 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: A history of NYHA class II, III, or IV CHF clinically significant arrhythmia 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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Nicole R Gonzales, MD

Organizational Affiliation

University of Texas Medical School-Houston

Official's Role

Principal Investigator

Facility Information:

Facility Name

Memorial Hermann Hospital

City

Houston

State/Province

Texas

ZIP/Postal Code

77030

Country

United States

12. IPD Sharing Statement

Citations:

PubMed Identifier

17457822

Citation

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. doi: 10.1002/ana.21097.

Results Reference

background

PubMed Identifier

19064796

Citation

Zhao X, Grotta J, Gonzales N, Aronowski J. Hematoma resolution as a therapeutic target: the role of microglia/macrophages. Stroke. 2009 Mar;40(3 Suppl):S92-4. doi: 10.1161/STROKEAHA.108.533158. Epub 2008 Dec 8.

Results Reference

background

Links:

URL

http://www.houstonstroke.com

Description

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