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Topiramate in Neonates Receiving Whole Body Cooling for Hypoxic Ischemic Encephalopathy

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ClinicalTrials.gov Identifier: NCT01765218
Recruitment Status : Recruiting
First Posted : January 10, 2013
Last Update Posted : July 22, 2020
Sponsor:
Information provided by (Responsible Party):
Kristin R Hoffman, University of California, Davis

Brief Summary:
The goal is to see whether topiramate (an anti-epileptic agent) improves the outcome of babies with neonatal hypoxic encephalopathy who are receiving whole body cooling.

Condition or disease Intervention/treatment Phase
Hypoxic Ischemic Encephalopathy Drug: Topiramate Drug: Placebo Phase 1 Phase 2

Detailed Description:
Hypoxic ischemic encephalopathy (HIE) is a devastating and unexpected disease in newborns that affects 1.5-2.6 per 1000 live births. Hypoxic ischemic encephalopathy has a mortality rate of up to 30% and survivors are at significant risk for adverse long-term outcomes, including seizures, cerebral palsy, and developmental delay. The investigators propose a randomized controlled study comparing therapeutic hypothermia alone, or therapeutic hypothermia combined with topiramate. The investigators hypothesize that adjuvant therapy with topiramate will reduce short term severity of HIE including seizures (the primary outcome), a composite HIE severity score, and reduce the time of normalization of the amplitude integrated EEG (aEEG). The investigators further hypothesize, that it will improve longer term outcomes such as developmental outcome. The primary hypothesis is that seizures before hospital discharge (or before 4 weeks post-natal age (which ever is earlier)) will be significantly reduced in the topiramate group compared to the control group

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 42 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Topiramate as an Adjuvant to Therapeutic Hypothermia for Infants With Hypoxic Ischemic Encephalopathy
Actual Study Start Date : February 2013
Estimated Primary Completion Date : May 2022
Estimated Study Completion Date : May 2022

Resource links provided by the National Library of Medicine

Drug Information available for: Topiramate

Arm Intervention/treatment
Placebo Comparator: Placebo
Subjects will receive the standard of care intervention for HIE at our institution (whole body cooling for 72h followed by gradual rewarming)
Drug: Placebo
A placebo identical in appearance to the active agent (topiramate)

Active Comparator: Topiramate
In addition to whole body cooling, infants assigned to the topiramate group will receive 5mg/kg of topiramate daily enterally for a total of 5 doses. The first dose will be administered as soon as possible on admission.
Drug: Topiramate
Infants assigned to the topiramate group will receive 5mg/kg of topiramate daily enterally for a total of 5 doses. The first dose will be administered as soon as possible on admission.
Other Names:
  • Topamax
  • Topiragen




Primary Outcome Measures :
  1. Seizures [ Time Frame: At 4 weeks post-natal age or the time of hospital discharge (whichever is earlier) ]
    Clinical or electrical seizures occuring before hospital discharge or before 4w post-natal age (which ever is earlier) will be compared between the topiramate and control groups.


Secondary Outcome Measures :
  1. HIE score [ Time Frame: At 4 weeks post-natal age or the time of hospital discharge (whichever is earlier) ]
    Differences in daily HIE score between the two groups will be compared from birth to day-5, and from birth to the time of discharge from hospital

  2. Normalization of aEEG [ Time Frame: At 4 weeks post-natal age or the time of hospital discharge (whichever is earlier) ]
    The time for normalization of aEEG voltages will be compared in the two groups.

  3. S100-beta levels [ Time Frame: Day of life 1, 3 and 7 ]
    Serum and urine S100beta levels (a marker of neuronal injury) will be compared in the two groups at three time points (on day of life 1, 3, and 7)

  4. MRI score [ Time Frame: On day 5-7 of life ]
    The MRI score on day 5 to 7 of life will be compared in the two groups.

  5. Developmental Outcome [ Time Frame: At 9, 18 and 27 months ]
    Bayley scales of infant development III will be compared in the two groups at 9, 18 and 27m of age



Information from the National Library of Medicine

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Ages Eligible for Study:   up to 6 Hours   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

In order to be eligible for cooling the baby must meet all three of the following sets of criteria

  1. Be near term (typically ≥34wks gestation) and be aged < 6h old
  2. Have signs of early perinatal depression (EITHER 10 minute Apgar score < 5, OR pH < 7.00 within 60mins of age, OR Base Excess < -12 within 60mins of age, OR need respiratory support at 10min of age due to respiratory depression)
  3. Have signs of moderate or severe encephalopathy based on either clinical examination or on amplitude integrated aEEG assessment

Exclusion Criteria:

  1. Known congenital myopathy
  2. Known congenital neuropathy

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): NCT01765218


Contacts
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Contact: Kristin R Hoffman, MD 916-734-3261 krhoffman@ucdavis.edu
Contact: Catherine Rottkamp, MD, PhD carottkamp@ucdavis.edu

Locations
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United States, California
UC Davis Medical Center Recruiting
Sacramento, California, United States, 95822
Contact: Kristin R Hoffman, MD    916-734-3261    krhoffman@ucdavis.edu   
Contact: Catherine Rottkamp, MD       carottkamp@ucdavis.edu   
Principal Investigator: Kristin R Hoffman, MD         
Sub-Investigator: Catherine Rottkamp, MD, PhD         
Sub-Investigator: Sameeia Iqbal, MD         
Sponsors and Collaborators
Kristin R Hoffman
Investigators
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Principal Investigator: Kristin R Hoffman, MD UC Davis
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Responsible Party: Kristin R Hoffman, Assistant Professor of Clinical Pediatrics, University of California, Davis
ClinicalTrials.gov Identifier: NCT01765218    
Other Study ID Numbers: 1182678
First Posted: January 10, 2013    Key Record Dates
Last Update Posted: July 22, 2020
Last Verified: July 2020
Keywords provided by Kristin R Hoffman, University of California, Davis:
Hypoxic ischemic encephalopathy
HIE
Perinatal depression
Whole body cooling
Therapeutic hypothermia
Additional relevant MeSH terms:
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Brain Diseases
Brain Ischemia
Hypoxia-Ischemia, Brain
Ischemia
Hypoxia
Pathologic Processes
Central Nervous System Diseases
Nervous System Diseases
Signs and Symptoms, Respiratory
Cerebrovascular Disorders
Vascular Diseases
Cardiovascular Diseases
Hypoxia, Brain
Topiramate
Anticonvulsants
Hypoglycemic Agents
Physiological Effects of Drugs