Preventing Brain Injury in Infants With Congenital Heart Disease

The recruitment status of this study is unknown because the information has not been verified recently.
Verified August 2011 by University of California, Davis.
Recruitment status was  Recruiting
Sponsor:
Information provided by (Responsible Party):
Mark Underwood, MD, University of California, Davis
ClinicalTrials.gov Identifier:
NCT01426542
First received: August 5, 2011
Last updated: August 29, 2011
Last verified: August 2011
  Purpose

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
Endpoint Classification: Safety/Efficacy Study
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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 2014
Estimated Primary Completion Date: December 2012 (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.

  Eligibility

Ages Eligible for Study:   up to 2 Months
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01426542

Contacts
Contact: Mark A Underwood, MD 916-762-7892 mark.underwood@ucdmc.ucdavis.edu
Contact: Kristin Hoffman, MD 916-762-2893 kristin.hoffman@ucdmc.ucdavis.edu

Locations
United States, California
UC Davis Children's Hospital Recruiting
Sacramento, California, United States, 95817
Contact: Majid Mirmiran, MD, PhD    916-734-4790    majid.mirmiran@ucdmc.ucdavis.edu   
Principal Investigator: Mark A Underwood, MD         
Sponsors and Collaborators
University of California, Davis
Investigators
Principal Investigator: Mark A Underwood, MD University of California, Davis
  More Information

No publications provided

Responsible Party: Mark Underwood, MD, Assistant Professor of Clinical Pediatrics, University of California, Davis
ClinicalTrials.gov Identifier: NCT01426542     History of Changes
Other Study ID Numbers: 216534
Study First Received: August 5, 2011
Last Updated: August 29, 2011
Health Authority: United States: Institutional Review Board

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

Additional relevant MeSH terms:
Heart Diseases
Heart Defects, Congenital
Brain Injuries
Cardiovascular Diseases
Cardiovascular Abnormalities
Congenital Abnormalities
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Craniocerebral Trauma
Trauma, Nervous System
Wounds and Injuries
Topiramate
Anticonvulsants
Central Nervous System Agents
Therapeutic Uses
Pharmacologic Actions
Neuroprotective Agents
Protective Agents
Physiological Effects of Drugs
Anti-Obesity Agents

ClinicalTrials.gov processed this record on July 31, 2014