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Preventing Brain Injury in Infants With Congenital Heart Disease

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ClinicalTrials.gov Identifier: NCT01426542
Recruitment Status : Active, not recruiting
First Posted : August 31, 2011
Last Update Posted : October 18, 2018
Sponsor:
Information provided by (Responsible Party):
University of California, Davis

Brief Summary:
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 or disease Intervention/treatment Phase
Cyanotic Congenital Heart Disease Drug: Topiramate Other: No medication, but routine heart surgery Phase 1

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.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 24 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
Official Title: Pilot Study of Topiramate Prophylaxis in Infants Undergoing Surgery for Congenital Heart Disease
Study Start Date : March 2011
Estimated Primary Completion Date : January 2019
Estimated Study Completion Date : January 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Heart Diseases
Drug Information available for: Topiramate

Arm Intervention/treatment
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




Primary Outcome Measures :
  1. 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 :
  1. 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.

  2. 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.



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Ages Eligible for Study:   up to 2 Months   (Child)
Sexes Eligible for Study:   All
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01426542


Locations
United States, California
UC Davis Children's Hospital
Sacramento, California, United States, 95817
Sponsors and Collaborators
University of California, Davis
Investigators
Principal Investigator: Mark A Underwood, MD University of California, Davis

Responsible Party: University of California, Davis
ClinicalTrials.gov Identifier: NCT01426542     History of Changes
Other Study ID Numbers: 216534
First Posted: August 31, 2011    Key Record Dates
Last Update Posted: October 18, 2018
Last Verified: October 2018

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

Additional relevant MeSH terms:
Heart Diseases
Heart Defects, Congenital
Cardiovascular Diseases
Cardiovascular Abnormalities
Congenital Abnormalities
Topiramate
Anticonvulsants
Neuroprotective Agents
Protective Agents
Physiological Effects of Drugs
Anti-Obesity Agents