Study of Citicoline for the Treatment of Traumatic Brain Injury (COBRIT)

Study Overview
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Brief Summary
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The Citicoline Brain Injury Treatment (COBRIT) is a randomized, double-blind, placebo controlled, multi-center trial of the effects of 90 days of citicoline on functional outcome in patients with complicated mild, moderate and severe traumatic brain injury.

Detailed Description
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Traumatic brain injury (TBI) is a major cause of death and disability. In the United States alone approximately 1.4 million sustain a TBI each year, of which 50,000 people die, and over 200,000 are hospitalized. Despite numerous prior clinical trials no standard pharmacotherapy for the treatment of TBI has been established in either the acute or post acute setting. Citicoline is a naturally occurring endogenous compound. This compound offers the potential of employing neuroprotection, neuro-recovery and neurofacilitation to enhance recovery after TBI. The primary goal of this study is to assess the efficacy of citicoline compared to placebo on functional and cognitive outcome in participants with traumatic brain injury.

Official Title
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Citicoline Brain Injury Treatment Trial

Conditions
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Traumatic Brain Injury

Intervention / Treatment
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* Drug: Placebo
* Drug: citicoline


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Non-penetrating traumatic brain injury. Age 18 (19 in Alabama) - 70 years. GCS criteria on/off paralytics as specified in protocol Reasonable expectation of completion of outcomes measures at a network center at six months post-injury. Able to swallow oral medication or, if unable to swallow, a gastric tube or peg are placed by 23 hours after injury. Reasonable expectation of enrollment within 24-hour time window. English-speaking Exclusion Criteria: Intubated patients with GCS motor score = 6 and not meeting CT criteria. Bilaterally fixed and dilated pupils Positive pregnancy test, known pregnancy, or currently breast feeding Evidence of diseases that interfere with outcome assessment Current acetylcholinesterase inhibitor use (Appendix 1) Imminent death or current life-threatening disease Currently enrolled in another study Prisoners

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

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: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Placebo<br>Placebo tablets formulated to resemble the citicoline treatment. | Drug: Placebo<br>* Drug Placebo Inactive twice a day given orally or enterally. The first dose is given within 24 hours of injury and treatment continues until 90 days or until the 90-day outcome assessment.<br>|
| Experimental: Citicoline<br>Experimental treatment administered orally or enterally depending upon whether the participant can swallow at 1,000 mg twice a day for 90 days or until the 90-day outcome assessment. | Drug: citicoline<br>* 1000 mg twice a day orally or enterally. The first dose is within 24 hours of injury and treatment continues for 90-days or until the 90-day outcome assessment.<br>* Other names: CDP-Choline, Cytidine 5-diphosphocholine, Somazina;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Functional and Cognitive Outcome | The primary outcome of this study was analyzed using a global statistic of the Network Core Battery. There were 9 scales: California Verbal Learning Test II (CVLT-II); Controlled Oral Word Association Test (COWAT); Digit Span (DS); Glasgow Outcome Scale Extended (GOSE); Processing Speed Index (PSI); Stroop Test 1 and 2 (ST1&2); and Trail Making Test part A and B (TMT parts A and B). Each scale was assigned cut-off for good outcome: GOSE>7, CVLT>36, PSI>85, TMT part A <42, TMT part B<138.1, DS>7.15, ST1<60.29, ST2<151.47, COWAT>32.5. Logistic regression was used to estimate the global OR. | 90 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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traumatic brain injury, cognition, behavioral outcome, functional outcome, treatment, early intervention, citicoline