Pilot Study of Head Cooling in Preterm Infants With Hypoxic Ischemic Encephalopathy

Study Overview
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Brief Summary
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The hypothesis is that premature infants' can have enough cooling applied to cool their brain to decrease CNS injury without cooling their body.

Detailed Description
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Hypoxic ischemic encephalopathy (HIE) is a potentially devastating disease of the newborn central nervous system (CNS) . Portions of the CNS are deprived of oxygen and blood flow for a period of time which may lead to permanent brain injury manifested as cerebral palsy as well as cognitive defects. Until recently no treatment has been shown to be effective for preventing brain damage, even though it has been demonstrated that the damage is progressive and that there is a window of opportunity to arrest some of the evolving brain injury. However, in May of 2007 the FDA approved the first device specifically designed to ameliorate brain damage in term babies with HIE. This head cooling device which was studied here at Vanderbilt under IRB protocol 990129 Brain Cooling for the treatment of perinatal hypoxic ischemic encephalopathy. We thus have eight years of experience of using this device in term infants. The results of the initial trial demonstrated a successful reduction of HIE induced brain injury from 66% in control infants to 55% in treated babies. There were no significant risks to the application of this device in term babies who are kept cool for 72 hours after experiencing an acute HIE event. The initial trials were limited to term babies because of concern that premature infants would be more at risk for hypothermia induced problems such as hypoglycemia,and coagulopathy. The concern about hypothermia in preterm infants remains a limiting consideration for doing whole body cooling in this population. We propose to apply the cooling cap to the heads of preterm infants who have experienced a significant HIE injury but maintain their body temperature in the normal range (36.1-37° C rectally). Infants will be cooled for up to 72 hours and will be tracked till discharge. Although this is a feasibility study, the participants will also be followed-up at 6, 12 and 24 months of age.

Official Title
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IRB# 070984 Pilot Study of Head Cooling in Preterm Infants With Hypoxic Ischemic Encephalopathy

Conditions
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Hypoxic Ischemic Encephalopathy

Intervention / Treatment
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* Device: Olympic Cool Cap


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Babies < 36 weeks gestation but > 32 0/7 weeks. These babies should be small enough to allow brain cooling with water circulating in a cooling cap applied to the surface of their head At least one of the following four criteria which are standard definitions for HIE: Apgar 0-3 at 1,5,10 minutes due to hypoxia pH less than 7.0 Base deficit greater than 15 Need for continued resuscitation due to hypoxia at 10 minutes AND a physical exam with evidence of hypotonia or lethargy or seizures indicative of evolving HIE. Intubated Age less than 6 hours Signed informed consent by parent / legal guardian Previous participant has been followed through 7 day head ultrasound. Exclusion Criteria: Mild HIE will not be cooled, therefore babies without hypotonia or lethargy and babies who are not intubated will be excluded. Gestational age ≥ 36 weeks or < 32 weeks or less than 1200 grams. Older than 6 hours of age Infant deemed in extremis on clinical exam. Survival not expected, i.e. received 3 intravenous doses of epinephrine or more during resuscitation; on infusion of dopamine, dobutamine and/or epinephrine at time of evaluation; and/or has fixed/dilated pupils. Evidence of head trauma or skull fracture causing major intracranial hemorrhage Intraventricular hemorrhage Weight less than the 5th percentile for gestational age Refusal of consent Imperforate anus

Ages Eligible for Study
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Minimum Age: 30 Minutes
Maximum Age: 6 Hours

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>Babies that meet criteria will be offered participation in feasibility trial, there are no other arms. | Device: Olympic Cool Cap<br>* Olympic Cool Cap will be applied to infants 32-35 weeks gestation who meet criteria for HIE.<br>* Other names: Selective Head Cooling;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Feasibility Trial- the Olympic Cool Cap Will be Applied, Can the Delivered Cap Temperature be Less Than 12 Degrees Without Changing Rectal Temperature. | Measurement of number of participants able to obtain 12 degree cap temperature | 60 minutes intervals up to 72 hours | 
| Cap Cooled to 12 Degrees Without Reducing Rectal Temperature | Yes/no | 6 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HIE, Cooling, Hypoxic ischemic encephalopathy, Neonatal encephalopathy, hypothermia