Mission Connect Mild Traumatic Brain Injury (TBI) Integrated Clinical Protocol

NCT01013870 | Terminated Phase 2 Results

• 1 other identifier: W81XWH-08-2-0132
• Study Type: interventional
• Target: 52
• Locations: 1 country
• Sites: 2

Brief Summary

The purpose of this study is to improve the ability to diagnose problems after mild traumatic brain injury (MTBI) and to test a drug that may improve the outcome from these injuries. Of the more than 1.5 million people who experience a traumatic brain injury (TBI) each year in the United States, as many as 75% sustain a mild TBI which can cause long-term or permanent impairments/disabilities in a significant proportion of patients. In addition, traumatic brain injury has become a signature injury of the wars in Iraq and Afghanistan. For people with these injuries, it is difficult to determine whether symptoms are due to the head injury or another condition, such as Post-traumatic Stress Disorder. In this project, there are 3 observational studies that involve testing of mental functions and behavior, imaging of the brain with special x-ray procedures, and blood samples to look at glandular function, which may be affected by head injury. A fourth study is a test of a drug, atorvastatin, which may provide protection for injured brain cells and improve outcome. By collecting and analyzing the information from these tests, it will be possible to make the process of diagnosing mild TBI or post traumatic stress disorder (PTSD) more precise, and also to see if atorvastatin is a helpful drug for patients with MTBI.

Conditions

Traumatic Brain Injury; Post-traumatic Stress Disorder

Keywords

mild traumatic brain injury; post-concussion syndrome; acute stress disorder; post-traumatic stress disorder; atorvastatin

Outcome Measures

Primary Outcomes (1)

• Rivermead Post-Concussion Symptoms Questionnaire, at 3 Months After Injury.

  The Rivermead Post-Concussive Symptoms Questionnaire (RPQ) is a 16-item self-report measure of the presence and severity of the 16 most commonly reported post-concussive symptoms found in the literature. The scale compares any current symptoms to pre-injury symptom levels to account for potential symptom exacerbation due to TBI. The range of scores is 0-64. Values for each of the 16 items include 0 (not experienced at all), 1 (no more of a problem than before the injury), 2 (mild problem), 3 (moderate problem), 4 (severe problem). The total score was a summation of symptoms that represented new symptom onset or an exacerbation of a symptom present pre-injury. (King, N.S., Crawford, S., Wenden, F.J., Moss, N.E., \& Wade, D.T. \[1995\]. The Rivermead Post Concussion Symptoms Questionnaire: A Measure of Symptoms Commonly Experiences after Head Injury and its Reliability. Journal of Neurology 242: 587-92.)

  3 months after injury

Secondary Outcomes (8)

• Medical Outcome Study Short Form 12 - Mental Score

  3 months

• Medical Outcome Study Short Form 12 - Physical Score

  3 months after injury

• Post-traumatic Stress Checklist - Civilian Form

  3 months after injury

• Connor Davidson Resilience Measure

  3 months after injury

• Center for Epidemiological Study Depression Scale

  3 months after injury

Study Arms (2)

MTBI subjects randomized to drug

EXPERIMENTAL

Of 200 MTBI subjects enrolled, 1:1 randomization will be used to assign half (i.e 100) to the treatment arm of the phase II drug trial of atorvastatin. These subjects will receive a daily weight-based dose of atorvastatin 1mg/kg (up to 80 mg) for seven days and started within 24 hours of MTBI, and their outcome will be compared with the group of subjects receiving a placebo. NOTE: The 100 Orthopedic Injury subjects recruited for and participating in the Observational studies are not included in the Medication study portion of this protocol.

Drug: Atorvastatin

MTBI subjects randomized to placebo

PLACEBO COMPARATOR

Of 200 MTBI subjects enrolled, 1:1 randomization will be used to assign half (i.e 100) to the placebo arm of the phase II drug trial of atorvastatin. These subjects will receive a daily dose of an inert preparation, visually indistinguishable from the active agent. They will take this preparation for seven days, started within 24 hours of MTBI, and their outcome will be compared with the group of subjects receiving active drug. NOTE: The 100 Orthopedic Injury subjects recruited for and participating in the Observational studies are not included in the Medication study portion of this protocol.

Drug: Placebo

Interventions

Atorvastatin DRUG

In this Phase II randomized clinical trial of 200 MTBI subjects to evaluate atorvastatin as a neuroprotective agent, subjects will receive either active drug or placebo (1:1 randomization) for 7 days, starting within 24 hours of the brain injury. The dosage for subjects in the treatment group will be weight-based at 1mg/kgm, up to 80 mg, which will be the maximal dose. Subjects will be monitored at 3-4 days after injury by phone, then with follow-up visits at 1 week, 1 month, 3 months.

Also known as: Lipitor®

MTBI subjects randomized to drug

Placebo DRUG

In this Phase II randomized clinical trial of 200 MTBI subjects to evaluate atorvastatin as a neuroprotective agent, subjects will receive either active drug or placebo (1:1 randomization) for 7 days, starting within 24 hours of the brain injury. For the placebo group, subjects will take a daily dose of an inert preparation, visually indistinguishable from the active agent. They will take this preparation for seven days, started within 24 hours of MTBI, and their outcome will be compared with the group of subjects receiving active drug. Subjects will be monitored at 3-4 days after injury by phone, then with follow-up visits at 1 week, 1 month, 3 months.

MTBI subjects randomized to placebo

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• age 18-50 years
• MTBI subjects: evidence of closed head injury; Glasgow Coma Score 13-15; loss of consciousness \< 30 minutes; post-traumatic amnesia \< 24 hours; Abbreviated Injury Score \</= 3 for any body region; absence of focal lesions on head CT scan
• Orthopedic Injury subjects: evidence of traumatic injury, other than head; Abbreviated Injury Score \</= 3 for any body region
• does not require hospitalization for injuries
• visual acuity and hearing adequate to participate in testing
• fluent in either English or Spanish

You may not qualify if:

• Abbreviated Injury Score \> 3 for any body region
• any type of penetrating injury
• history of significant pre-existing disease or systemic injuries
• history of schizophrenia or bipolar disorder
• blood alcohol \> 200 mL/dL
• left-handed
• existing contraindications for MRI
• claustrophobia
• pregnancy

Sponsors & Collaborators

• Baylor College of Medicine: lead
• The University of Texas Health Science Center, Houston: collaborator

Study Sites (2)

Baylor College of Medicine/Ben Taub General Hospital

Houston, Texas, 77030, United States

Location

University of Texas Health Science Center at Houston/Memorial Hermann Hospital

Houston, Texas, 77030, United States

Location

Related Publications (6)

• King NS, Crawford S, Wenden FJ, Moss NE, Wade DT. The Rivermead Post Concussion Symptoms Questionnaire: a measure of symptoms commonly experienced after head injury and its reliability. J Neurol. 1995 Sep;242(9):587-92. doi: 10.1007/BF00868811.

  PMID: 8551320 BACKGROUND

• Connor KM, Davidson JR. Development of a new resilience scale: the Connor-Davidson Resilience Scale (CD-RISC). Depress Anxiety. 2003;18(2):76-82. doi: 10.1002/da.10113.

  PMID: 12964174 BACKGROUND

• Ware JE Jr., Kosinski M, Turner-Bowker DM, Gandek B. How to Score Version 2 of the SF-12v2® Health Survey [With a Supplement Documenting SF-12® Health Survey] Lincoln, RI: QualityMetric Incorporated, 2002

  BACKGROUND

• Weathers F, Litz B, Herman D, Huska J, Keane T. The PTSD Checklist [PCL]: Reliability, Validity, and Diagnostic Utility. Paper presented at the Annual Convention of the International Society for Traumatic Stress Studies, San Antonio, TX., October 1993

  BACKGROUND

• Radloff LS. The CES-D Scale: A self-report depression scale for research in the general population. App Psychol Meas. 1977;1:385-401.

  BACKGROUND

• Robertson CS, McCarthy JJ, Miller ER, Levin H, McCauley SR, Swank PR. Phase II Clinical Trial of Atorvastatin in Mild Traumatic Brain Injury. J Neurotrauma. 2017 Apr 1;34(7):1394-1401. doi: 10.1089/neu.2016.4717. Epub 2017 Feb 27.

  PMID: 28006970 DERIVED

MeSH Terms

Conditions

Brain Injuries, Traumatic; Stress Disorders, Post-Traumatic; Brain Concussion; Post-Concussion Syndrome; Stress Disorders, Traumatic, Acute

Interventions

Atorvastatin

Condition Hierarchy (Ancestors)

Brain Injuries; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Craniocerebral Trauma; Trauma, Nervous System; Wounds and Injuries; Stress Disorders, Traumatic; Trauma and Stressor Related Disorders; Mental Disorders; Head Injuries, Closed; Wounds, Nonpenetrating

Intervention Hierarchy (Ancestors)

Pyrroles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heptanoic Acids; Fatty Acids; Lipids

Results Point of Contact

• Title: Claudia Robertson, MD
• Organization: Baylor College of Medicine

claudiar@bcm.edu

713-873-2792

Study Officials

• Claudia S Robertson, MD

  Baylor College of Medicine

  PRINCIPAL INVESTIGATOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor, Department of Neurosurgery

Study Record Dates

• First Submitted: November 13, 2009
• First Posted: November 16, 2009
• Study Start: February 1, 2010
• Primary Completion: March 1, 2015
• Study Completion: June 1, 2015
• Last Updated: January 9, 2017
• Results First Posted: November 17, 2016

Record last verified: 2016-11

Data Sharing

• IPD Sharing: Will share

Locations

US (2)