Design of a prospective, dose-escalation study evaluating the Safety of Pioglitazone for Hematoma Resolution in Intracerebral Hemorrhage (SHRINC)

Nicole R. Gonzales, Jharna Shah, Navdeep Sangha, Lenis Sosa, Rebecca Martinez, Loren Shen, Mallikarjunarao Kasam, Miriam M. Morales, M. Monir Hossain, Andrew D. Barreto, Sean I. Savitz, George Lopez, Vivek Misra, Tzu Ching Wu, Ramy El Khoury, Amrou Sarraj, Preeti Sahota, William Hicks, Indrani Acosta, M. Rick SlineMohammad H. Rahbar, Xiurong Zhao, Jaroslaw Aronowski, James C. Grotta

Research output: Contribution to journalArticle

51 Scopus citations

Abstract

Rationale: Preclinical work demonstrates that the transcription factor peroxisome proliferator-activated receptor gamma plays an important role in augmenting phagocytosis while modulating oxidative stress and inflammation. We propose that targeted stimulation of phagocytosis to promote efficient removal of the hematoma without harming surrounding brain cells may be a therapeutic option for intracerebral hemorrhage. Aims: The primary objective is to assess the safety of the peroxisome proliferator-activated receptor gamma agonist, pioglitazone, in increasing doses for three-days followed by a maintenance dose, when administered to patients with spontaneous intracerebral hemorrhage within 24h of symptom onset compared with standard care. We will determine the maximum tolerated dose of pioglitazone. Study design: This is a prospective, randomized, blinded, placebo-controlled, dose-escalation safety trial in which patients with spontaneous intracerebral hemorrhage are randomly allocated to placebo or treatment. The Continual Reassessment Method for dose finding is used to determine the maximum tolerated dose of pioglitazone. Hematoma and edema resolution is evaluated with serial magnetic resonance imaging (MRI) at specified time points. Functional outcome will be evaluated at three- and six-months. Outcomes: The primary safety outcome is mortality at discharge. Secondary safety outcomes include mortality at three-months and six-months, symptomatic cerebral edema, clinically significant congestive heart failure, edema, hypoglycemia, anemia, and hepatotoxicity. Radiographic outcomes will explore the time frame for resolution of 25%, 50%, and 75% of the hematoma. Clinical outcomes are measured by the National Institutes of Health Stroke Scale (NIHSS), the Barthel Index, modified Rankin Scale, Stroke Impact Scale-16, and EuroQol at three- and six-months.

Original languageEnglish (US)
Pages (from-to)388-396
Number of pages9
JournalInternational Journal of Stroke
Volume8
Issue number5
DOIs
StatePublished - Jul 2013

Keywords

  • Clinical trial
  • Intracerebral hemorrhage
  • MRI
  • Pioglitazone
  • Protocol
  • Therapy

ASJC Scopus subject areas

  • Neurology

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