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

October 1, 2015 updated by: Nicole Gonzales, The University of Texas Health Science Center, Houston
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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

84

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

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

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years to 78 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 1
Drug: Pioglitazone
Escalating doses for 3 days, then 30 mg orally daily for the duration of the study as determined by MRI
Other Names:
  • Actos
Placebo Comparator: 2
Drug: Placebo Control
Lactose Capsule administered by mouth daily for the duration of the study as determined by MRI

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
The primary measure of safety will be mortality at discharge.
Time Frame: At hospital discharge or Day 14, whichever occurs first.
At hospital discharge or Day 14, whichever occurs first.

Secondary Outcome Measures

Outcome Measure
Time Frame
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
3 months, 6 months, and during hospitalization

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

The University of Texas Health Science Center, Houston

Investigators

  • Principal Investigator: Nicole R Gonzales, MD, University of Texas Medical School-Houston

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

March 1, 2009

Primary Completion (Actual)

April 1, 2013

Study Completion (Actual)

November 1, 2013

Study Registration Dates

First Submitted

January 21, 2009

First Submitted That Met QC Criteria

January 22, 2009

First Posted (Estimate)

January 23, 2009

Study Record Updates

Last Update Posted (Estimate)

October 2, 2015

Last Update Submitted That Met QC Criteria

October 1, 2015

Last Verified

October 1, 2015

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • HSC-MS-08-0410
  • P50 NS044227-5

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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