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

Study Description

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Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Traumatic Brain Injury	Drug: Placebo; Drug: citicoline	Phase 3

Detailed Description:

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.

Study Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	1213 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:	Treatment
Official Title:	Citicoline Brain Injury Treatment Trial
Study Start Date :	July 2007
Actual Primary Completion Date :	May 2011
Actual Study Completion Date :	May 2011

Arms and Interventions

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Arm	Intervention/treatment
Experimental: Placebo; Placebo tablets formulated to resemble the citicoline treatment.	Drug: Placebo; 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.
Experimental: Citicoline; 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; 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.; Other Name: CDP-Choline, Cytidine 5-diphosphocholine, Somazina

Outcome Measures

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Primary Outcome Measures :

1. Functional and Cognitive Outcome [ Time Frame: 90 days ]
   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.

Eligibility Criteria

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Ages Eligible for Study:	18 Years to 70 Years (Adult, Senior)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

1. Non-penetrating traumatic brain injury.
2. Age 18 (19 in Alabama) - 70 years.
3. GCS criteria on/off paralytics as specified in protocol
4. Reasonable expectation of completion of outcomes measures at a network center at six months post-injury.
5. Able to swallow oral medication or, if unable to swallow, a gastric tube or peg are placed by 23 hours after injury.
6. Reasonable expectation of enrollment within 24-hour time window.
7. English-speaking

Exclusion Criteria:

1. Intubated patients with GCS motor score = 6 and not meeting CT criteria.
2. Bilaterally fixed and dilated pupils
3. Positive pregnancy test, known pregnancy, or currently breast feeding
4. Evidence of diseases that interfere with outcome assessment
5. Current acetylcholinesterase inhibitor use (Appendix 1)
6. Imminent death or current life-threatening disease
7. Currently enrolled in another study
8. Prisoners

Contacts and Locations

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Locations

United States, Alabama
University of Alabama at Birmingham
Birmingham, Alabama, United States, 35294-3295
United States, Maryland
University of Maryland, Baltimore
Baltimore, Maryland, United States, 21201
United States, Pennsylvania
Temple University
Philadelphia, Pennsylvania, United States, 19141-3099
University of Pittsburgh
Pittsburgh, Pennsylvania, United States, 15213-3221
United States, Tennessee
University of Tennessee Health Sciences Center
Memphis, Tennessee, United States, 38163
United States, Texas
University of Texas, Southwestern Medical Center
Dallas, Texas, United States, 75390
United States, Virginia
Virginia Commonwealth University
Richmond, Virginia, United States, 23298-0677
United States, Washington
University of Washington
Seattle, Washington, United States, 23298-0631

Sponsors and Collaborators

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Investigators

Principal Investigator:	Sherry Melton, MD	University of Alabama at Birmingham
Principal Investigator:	Howard Eisenberg, MD	University of Maryland
Principal Investigator:	Jack Jallo, MD, PhD	Temple University
Principal Investigator:	Joseph Ricker, PhD	University of Pittsburgh
Principal Investigator:	Shelly Timmons, MD, PhD	University of Tennessee Health Sciences Center
Principal Investigator:	Ramon Diaz-Arrastia, MD, PhD	University of Texas Southwestern Medical Center
Principal Investigator:	John Ward, MD	Virginia Commonwealth University
Principal Investigator:	Nancy Temkin, PhD	University of Washington
Study Director:	Beth Ansel, PhD	National Institute of Child Health and Human Development, National Center for Medical Rehabilitation Research
Principal Investigator:	William Friedewald, MD	Columbia University Department of Biostatistics

More Information

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Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Zafonte RD, Bagiella E, Ansel BM, Novack TA, Friedewald WT, Hesdorffer DC, Timmons SD, Jallo J, Eisenberg H, Hart T, Ricker JH, Diaz-Arrastia R, Merchant RE, Temkin NR, Melton S, Dikmen SS. Effect of citicoline on functional and cognitive status among patients with traumatic brain injury: Citicoline Brain Injury Treatment Trial (COBRIT). JAMA. 2012 Nov 21;308(19):1993-2000. doi: 10.1001/jama.2012.13256.

Responsible Party:	William Friedewald, Professor, Columbia University
ClinicalTrials.gov Identifier:	NCT00545662 History of Changes
Other Study ID Numbers:	BA-HD042; HD042687-04; HD042738-05; HD042678-03; HD042653-05; HD042689-05; HD042736-04; HD 042686-01A1; HD042652-04; HD042823-05
First Posted:	October 17, 2007
Results First Posted:	December 19, 2012
Last Update Posted:	December 19, 2012
Last Verified:	November 2012

Keywords provided by William Friedewald, Columbia University:

traumatic brain injury; cognition; behavioral outcome; functional outcome	treatment; early intervention; citicoline

Additional relevant MeSH terms:

Wounds and Injuries; Brain Injuries; Brain Injuries, Traumatic; Brain Diseases; Central Nervous System Diseases	Nervous System Diseases; Craniocerebral Trauma; Trauma, Nervous System; Cytidine Diphosphate Choline; Nootropic Agents