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

Citicoline Brain Injury Treatment Trial

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.

Study Overview

• Status: Terminated
• Conditions: Traumatic Brain Injury
• Intervention / Treatment: Drug: Placebo; Drug: citicoline

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 Type: Interventional
• Enrollment (Actual): 1213
• Phase: Phase 3

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / 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 Names: CDP-Choline, Cytidine 5-diphosphocholine, Somazina

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: 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, Baltimore; 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

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: July 1, 2007
• Primary Completion (Actual): May 1, 2011
• Study Completion (Actual): May 1, 2011

Study Registration Dates

• First Submitted: October 16, 2007
• First Submitted That Met QC Criteria: October 16, 2007
• First Posted (Estimate): October 17, 2007

Study Record Updates

• Last Update Posted (Estimate): December 19, 2012
• Last Update Submitted That Met QC Criteria: November 16, 2012
• Last Verified: November 1, 2012

More Information

Terms related to this study

• Keywords: treatment; cognition; early intervention; traumatic brain injury; functional outcome; citicoline; behavioral outcome
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Craniocerebral Trauma; Trauma, Nervous System; Brain Injuries; Wounds and Injuries; Brain Injuries, Traumatic; Molecular Mechanisms of Pharmacological Action; Antimetabolites; Gastrointestinal Agents; Hypolipidemic Agents; Lipid Regulating Agents; Nootropic Agents; Lipotropic Agents; Choline; Cytidine Diphosphate Choline
• 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