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

NCT00545662 | Terminated Phase 3 Results DMC

• 10 other identifiers: BA-HD042HD042687-04HD042738-05HD042678-03HD042653-05HD042689-05HD042736-04HD 042686-01A1HD042652-04HD042823-05
• Study Type: interventional
• Target: 1,213
• Locations: 1 country
• Sites: 8

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.

Conditions

Traumatic Brain Injury

Keywords

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

Outcome Measures

Primary Outcomes (1)

• 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

Study Arms (2)

Placebo

EXPERIMENTAL

Placebo tablets formulated to resemble the citicoline treatment.

Drug: Placebo

Citicoline

EXPERIMENTAL

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

Interventions

Placebo DRUG

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.

Placebo

citicoline DRUG

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.

Also known as: CDP-Choline, Cytidine 5-diphosphocholine, Somazina

Citicoline

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

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

Study Sites (8)

University of Alabama at Birmingham

Birmingham, Alabama, 35294-3295, United States

Location

University of Maryland, Baltimore

Baltimore, Maryland, 21201, United States

Location

Temple University

Philadelphia, Pennsylvania, 19141-3099, United States

Location

University of Pittsburgh

Pittsburgh, Pennsylvania, 15213-3221, United States

Location

University of Tennessee Health Sciences Center

Memphis, Tennessee, 38163, United States

Location

University of Texas, Southwestern Medical Center

Dallas, Texas, 75390, United States

Location

Virginia Commonwealth University

Richmond, Virginia, 23298-0677, United States

Location

University of Washington

Seattle, Washington, 23298-0631, United States

Location

Related Publications (1)

• 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.

  PMID: 23168823 DERIVED

MeSH Terms

Conditions

Brain Injuries, Traumatic

Interventions

Cytidine Diphosphate Choline

Condition Hierarchy (Ancestors)

Brain Injuries; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Craniocerebral Trauma; Trauma, Nervous System; Wounds and Injuries

Intervention Hierarchy (Ancestors)

Choline; Trimethyl Ammonium Compounds; Quaternary Ammonium Compounds; Amines; Organic Chemicals; Onium Compounds; Cytidine Diphosphate; Cytosine Nucleotides; Pyrimidine Nucleotides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleotides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleotides

Results Point of Contact

• Title: Dr. William Friedewald
• Organization: Columbia University

wtf1@columbia.edu

212-305-3017

Study Officials

• 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

  PRINCIPAL INVESTIGATOR

• Beth Ansel, PhD

  National Institute of Child Health and Human Development, National Center for Medical Rehabilitation Research

  STUDY DIRECTOR

• William Friedewald, MD

  Columbia University Department of Biostatistics

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: October 16, 2007
• First Posted: October 17, 2007
• Study Start: July 1, 2007
• Primary Completion: May 1, 2011
• Study Completion: May 1, 2011
• Last Updated: December 19, 2012
• Results First Posted: December 19, 2012

Record last verified: 2012-11

Locations

US (8)