Cyanotic Congenital Heart DiseasePhase 1NCT01426542
Preventing Brain Injury in Infants With Congenital Heart Disease
A Phase 1 study testing Topiramate and No medication, but routine heart surgery in people with Cyanotic Congenital Heart Disease, run by University of California, Davis at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages Up to 2 months
- Conditions the study is for
- Cyanotic Congenital Heart Disease
- What is being tested?
- Topiramate and No medication, but routine heart surgery
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 24 participants
- Where
- 1 siteUnited States
- Study dates
- Mar 2011to 28 Jul 2017
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Up to 2 months
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Age less than 2 months
- Cyanotic congenital heart disease requiring surgery
Who cannot join
- Genetic syndromes with high risk of neurodevelopmental delay
- Gestational age less than 35 weeks at birth
- Multiple organ failure or multiple organ anomalies
Trial locations and contacts
1 site in 1 country.
United States1 site
UC Davis Children's Hospital
Sacramento, California, 95817
About this study
Official title: Pilot Study of Topiramate Prophylaxis in Infants Undergoing Surgery for Congenital Heart Disease
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.
Read the 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.
- Conditions
- Cyanotic Congenital Heart Disease
- Being tested
- Topiramate, No medication, but routine heart surgery
- Keywords
- brain injury, stroke, cerebral palsy, seizures
- Medical subject headings
- Brain Injuries, Stroke, Cerebral Palsy, Seizures
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TopiramateDrug
Topiramate 5 mg/kg by mouth (or by feeding tube) once a day for one week before and one week after heart surgery.
No medication, but routine heart surgeryOther
No medication, but routine heart surgery
| Study group | Role | What they receive |
|---|---|---|
| Topiramate | Experimental | Not described Receives: Drug: Topiramate |
| Control | Active comparator | These infants will undergo surgery, but will not receive topiramate Receives: Other: No medication, but routine heart surgery |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change from baseline in Plasma S100B
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.
Measured: 1 week before surgery, 1 day and 1 week after surgery
Secondary outcomes (2)
Mullen Scales of Early Learning
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.
Measured: 18 months of age
Changes from baseline in urine metabolomics
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.
Measured: 1 week before surgery, 1 day and 1 week after surgery
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Aug 2011 (estimated)
- Study startMar 2011
- Primary completion28 Jul 2017
- Study completion28 Jul 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Cyanotic Congenital Heart DiseaseStudies of the same condition, open and under way.
- More trials run by University of California, DavisThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Prevention
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 24 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of California, Davis
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Mark A Underwood, MD, Principal investigator, University of California, Davis
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01426542
- Sponsor's protocol ID
- 216534
- Status last verified
- Feb 2019
- First submitted
- 5 Aug 2011
- Last updated
- 8 Feb 2019
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 8 Feb 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pilot Study of Topiramate Prophylaxis in Infants Undergoing Surgery for Congenital Heart Disease
- ClinicalTrials.gov ID
- NCT01426542
- Acronym / sponsor ID
- 216534
- Conditions
- Cyanotic Congenital Heart Disease
- Keywords
- brain injury, stroke, cerebral palsy, seizures
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 24 participants (actual)
- Lead sponsor
- University of California, DavisUniversity, hospital or other
- Study start
- Mar 2011
- Primary completion
- 28 Jul 2017 (actual)
- Study completion
- 28 Jul 2017 (actual)
- First posted
- 31 Aug 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Prevention
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Topiramate | Experimental | Drug: Topiramate |
| Control | Active comparator | Other: No medication, but routine heart surgeryThese infants will undergo surgery, but will not receive topiramate |
Who may qualify
- Ages
- Up to 2 months
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (2 listed)
- Age less than 2 months
- Cyanotic congenital heart disease requiring surgery
Key exclusion criteria (3 listed)
- Genetic syndromes with high risk of neurodevelopmental delay
- Gestational age less than 35 weeks at birth
- Multiple organ failure or multiple organ anomalies
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TopiramateTopiramate 5 mg/kg by mouth (or by feeding tube) once a day for one week before and one week after heart surgery. | Drug | Topiramate |
| No medication, but routine heart surgeryNo medication, but routine heart surgery | Other | Control |
Primary outcome
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.
2 secondary outcomes
Mullen Scales of Early Learning
Time frame: 18 months of age
Changes from baseline in urine metabolomics
Time frame: 1 week before surgery, 1 day and 1 week after surgery
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Feb 2019.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Mark A Underwood, MD principal investigator
University of California, Davis
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Topiramate and No medication, but routine heart surgery in people with Cyanotic Congenital Heart Disease, run by University of California, Davis at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 8 Feb 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change from baseline in Plasma S100B (time frame: 1 week before surgery, 1 day and 1 week after surgery). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Feb 2019.