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Preventing Brain Injury in Infants With Congenital Heart Disease

The recruitment status of this study is unknown. The completion date has passed and the status has not been verified in more than two years.
Verified November 2014 by University of California, Davis.
Recruitment status was:  Recruiting
Information provided by (Responsible Party):
Mark Underwood, MD, University of California, Davis Identifier:
First received: August 5, 2011
Last updated: November 28, 2014
Last verified: November 2014
Newborn babies with congenital heart disease often require surgery in the first month of life. The risks of brain damage from congenital heart disease and from the various corrective surgeries are high because of poor levels of oxygen reaching the brain. Topiramate is an anti-convulsant medication that protects brain cells from damage due to low amounts of oxygen in animal studies. The investigators hypothesize that giving topiramate to babies with congenital heart disease before and after surgery will decrease the amount of brain damage caused by the heart disease and/or the surgery to correct the heart disease.

Condition Intervention Phase
Cyanotic Congenital Heart Disease
Drug: Topiramate
Other: No medication, but routine heart surgery
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Prevention
Official Title: Pilot Study of Topiramate Prophylaxis in Infants Undergoing Surgery for Congenital Heart Disease

Resource links provided by NLM:

Further study details as provided by University of California, Davis:

Primary Outcome Measures:
  • Change from baseline in Plasma S100B [ Time Frame: 1 week before surgery, 1 day and 1 week after surgery ]
    Baseline plasma S100B levels will be determined prior to surgery (at enrollment) with repeat levels at the two timepoints after surgery. Main outcome will be change from baseline.

Secondary Outcome Measures:
  • Mullen Scales of Early Learning [ Time Frame: 18 months of age ]
    This broad assessment of neurodevelopment includes five scales: Gross Motor, Visual Reception, Fine Motor, Expressive Language, and Receptive Language, with further testing if needed to explore deficits.

  • Changes from baseline in urine metabolomics [ Time Frame: 1 week before surgery, 1 day and 1 week after surgery ]
    Urine specimens obtained at enrollment and at the two time points after surgery will be assessed for a broad range of metabolites (complex molecules). Changes from baseline will be evaluated.

Estimated Enrollment: 24
Study Start Date: June 2011
Estimated Study Completion Date: June 2015
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Topiramate Drug: Topiramate
Topiramate 5 mg/kg by mouth (or by feeding tube) once a day for one week before and one week after heart surgery.
Active Comparator: Control
These infants will undergo surgery, but will not receive topiramate
Other: No medication, but routine heart surgery
No medication, but routine heart surgery

Detailed Description:
Infants with cyanotic congenital heart disease undergoing surgery in the neonatal period have a high rate of brain injury resulting in seizures, stroke, cerebral palsy, and neurodevelopmental delays. Neuroimaging abnormalities are found in 30% to 60% of cases and neurodevelopmental impairments occur in more than half of these children. The mechanisms of brain injury in these children are not fully understood. Experimental animal models have shown that the abundant release of glutamate in the brain during hypoxic-ischemic insult results in brain injury. Blocking glutamate receptors by administration of the anticonvulsant topiramate has been shown to prevent such injury in animal studies. This study is an open pilot trial of peri-operative topiramate administration to infants with cyanotic congenital heart disease to test the feasibility of this approach and generate preliminary data about markers of brain injury (serum S100B levels and urine metabolomics) and neurodevelopment at 18 months of age. If the approach is feasible and the preliminary data are encouraging a larger efficacy trial will be designed. Although topiramate has been used in neonates and infants to treat seizures and in a pilot study in term infants with hypoxic-ischemic encephalopathy, this is the first study of its effects on markers of brain injury and neurologic outcomes in infants with cyanotic congenital heart disease.

Ages Eligible for Study:   up to 2 Months   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Age less than 2 months
  • Cyanotic congenital heart disease requiring surgery

Exclusion Criteria:

  • Genetic syndromes with high risk of neurodevelopmental delay
  • Gestational age less than 35 weeks at birth
  • Multiple organ failure or multiple organ anomalies
  Contacts and Locations
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Please refer to this study by its identifier: NCT01426542

Contact: Mark A Underwood, MD 916-762-7892
Contact: Kristin Hoffman, MD 916-762-2893

United States, California
UC Davis Children's Hospital Recruiting
Sacramento, California, United States, 95817
Contact: Majid Mirmiran, MD, PhD    916-734-4790   
Principal Investigator: Mark A Underwood, MD         
Sponsors and Collaborators
University of California, Davis
Principal Investigator: Mark A Underwood, MD University of California, Davis
  More Information

Responsible Party: Mark Underwood, MD, Assistant Professor of Clinical Pediatrics, University of California, Davis Identifier: NCT01426542     History of Changes
Other Study ID Numbers: 216534
Study First Received: August 5, 2011
Last Updated: November 28, 2014

Keywords provided by University of California, Davis:
brain injury
cerebral palsy

Additional relevant MeSH terms:
Heart Diseases
Heart Defects, Congenital
Cardiovascular Diseases
Cardiovascular Abnormalities
Congenital Abnormalities
Neuroprotective Agents
Protective Agents
Physiological Effects of Drugs
Anti-Obesity Agents processed this record on April 21, 2017