Role of Citicoline in Treatment of Newborns With Hypoxic Ischemic Encephalopathy

Study Overview
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Brief Summary
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Citicoline, is a naturally occurring compound and an intermediate in the metabolism of phosphatidylcholine. Phosphatidylcholine is an important component of the phospholipids of the cell membranes. Citicoline is composed of two molecules: cyti¬dine and choline. Both these molecules enter the brain separately and by passing through the blood-brain barrier where they act as substrates for intracellular synthesis of CDP-choline . This drug has been widely used in adults who suffer from acute ischemic strokes for than 4 decades with good results and has been proved to have a very good safety profile as well. It has various therapeutic effects at several stages of the ischemic cascade in acute ischemic stroke. It stabilizes cell membranes by increasing phosphatidylcholine and sphingomyelin synthesis and by inhibiting the release of free fatty acids . By protecting membranes, citicoline inhibits glutamate release during ischemia. In an experimental model of ischemia in the rat, citicoline treatment decreased glutamate levels and stroke size. Citicoline favors the synthesis of nucleic acids, proteins, acetylcholine and other neurotransmitters, and decreases free radical formation Therefore, citicoline simultaneously inhibits different steps of the ischemic cascade protecting the injured tissue against early and delayed mechanisms responsible for ischemic brain injury. citicoline may facilitate recovery by enhancing synaptic outgrowth and increased neuroplasticity with decrease of neurologic deficits and improvement of behavioral performance. Considering these pharmacologic properties of citicoline, we are planning to see its effects in newborns who have HIE which causes a global acute ischemic changes in developing brain.

Official Title
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Role of Citicoline in Treatment of Newborns With Hypoxic Ischemic Encephalopathy

Conditions
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Hypoxic-Ischemic Encephalopathy

Intervention / Treatment
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* Drug: citicoline


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: • Newborn babies having grade 2 and 3 HIE, of both genders delivered in labor room or operation theatre of our hospital. Outdoor patients presenting within 24 hours of delivery Exclusion Criteria: • Outborn babies presenting after 24 hours of delivery. Patients with severe congenital malformations Babies born extremely prematurely (less than 28 weeks)

Ages Eligible for Study
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Minimum Age: 1 Hour
Maximum Age: 14 Days

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
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: control group<br>newborns with hypoxic ischemic encephalopathy grade 2/3 who will receive only supportive care | |
| Experimental: study group<br>newborns with hypoxic ischemic encephalopathy grade 2/3 who will receive citicoline along with supportive care | Drug: citicoline<br>* intravenous citicoline 15 mg per kg per dose BD will be given to babies until oral feeds are established<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| effect on sucking | time to establish full oral feeds | 06 months after start of study | 
| discharge time | time to discharge from hospital | 06 months after start of study | 
| effect on seizures | duration of seizures | 06 months after start of study |