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

This study has been terminated.
(inability to recruit adequate numbers of subjects)
Sponsor:
Collaborator:
The University of Texas Health Science Center, Houston
Information provided by (Responsible Party):
Claudia Sue Robertson, Baylor College of Medicine
ClinicalTrials.gov Identifier:
NCT01013870
First received: November 13, 2009
Last updated: September 27, 2016
Last verified: September 2016
  Purpose
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.

Condition Intervention Phase
Traumatic Brain Injury
Post-traumatic Stress Disorder
Drug: Atorvastatin
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: The Mission Connect Mild TBI Translational Research Consortium's Integrated Clinical Protocol

Resource links provided by NLM:


Further study details as provided by Baylor College of Medicine:

Primary Outcome Measures:
  • Rivermead Post-Concussion Symptoms Questionnaire, at 3 Months After Injury. [ Time Frame: 3 months after injury ] [ Designated as safety issue: No ]
    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.)


Secondary Outcome Measures:
  • Medical Outcome Study Short Form 12 - Mental Score [ Time Frame: 3 months ] [ Designated as safety issue: No ]
    SF-12 is a self-report questionnaire that assesses functional health and well-being. There are 12 items in 8 subscales, including physical, bodily pain, general health, vitality, social functioning, role-emotional, and mental health. Physical and Mental Health Composite Scores are computed using the scores of the 12 questions and range from 0 to 100, where a zero score indicates the lowest level of health measured by the scales and 100 indicates the highest level of health. Both Physical and Mental Health Composite Scales combine the 12 items in such a way that they compare to a national norm with a mean score of 50.0 and a standard deviation of 10.0. (Ware, J.E., Jr., Kosinski, M., Turner-Bowker, D.M., 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.)

  • Medical Outcome Study Short Form 12 - Physical Score [ Time Frame: 3 months after injury ] [ Designated as safety issue: No ]
    SF-12 is a self-report questionnaire that assesses functional health and well-being. There are 12 items in 8 subscales, including physical, bodily pain, general health, vitality, social functioning, role-emotional, and mental health. Physical and Mental Health Composite Scores are computed using the scores of the 12 questions and range from 0 to 100, where a zero score indicates the lowest level of health measured by the scales and 100 indicates the highest level of health. Both Physical and Mental Health Composite Scales combine the 12 items in such a way that they compare to a national norm with a mean score of 50.0 and a standard deviation of 10.0. (Ware, J.E., Jr., Kosinski, M., Turner-Bowker, D.M., 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.)

  • Post-traumatic Stress Checklist - Civilian Form [ Time Frame: 3 months after injury ] [ Designated as safety issue: No ]
    The Post Traumatic Stress Disorder Checklist (PCL) is a 17-item self report measure of the DSM-IV symptoms of PTSD. Respondents rate how much they were "bothered by a symptom" on a 5-point scale ranging from 1 ("not at all") to 5 ("extremely"). The PCL was scored as a total score (range 17-85), with higher total scores indicating more symptoms. (Weathers, F., Litz, B., Herman, D., Huska, J., & Keane, T. [October 1993]. 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.)

  • Connor Davidson Resilience Measure [ Time Frame: 3 months after injury ] [ Designated as safety issue: No ]
    The Connor-Davidson Resilience scale (CD-RISC) has 25 items, each rated on a 5-point scale (0-4), with higher scores reflecting greater resilience. The sum score has a range from 0 to 100. (Conner KM, Davidson JR. Development of a new resilience scale: the Connor-Davidson Resilience Scale [CD-RISC]. Depress Anxiety 18[2]:76-82,2003].

  • Center for Epidemiological Study Depression Scale [ Time Frame: 3 months after injury ] [ Designated as safety issue: No ]
    The CES-D is a widely used screening scale for depression, assessing depressive feelings and behaviors occurring in the past week of a patient's life. The CES-D consists of 20 items, which make up six scales reflecting depressive symptomatology: depressed mood, feelings of guilt and worthlessness, feelings of helplessness and hopelessness, psychomotor retardation, loss of appetite, and sleep disturbance. Each item is scored on a 4-point scale ranging from 0 (rarely/none of the time) to 3 (most/all of the time). Scores for items 4, 8, 12, and 16 are reversed before summing all items to yield a total score, which can range from 0-60. Higher scores indicate more depressive symptoms. (Radloff, LS [1977]. The CES-D Scale: A self-report depression scale for research in the general population. App Psychol Meas, 1, 385-401.)

  • Brief Visuospatial Memory Test - Revised [ Time Frame: 3 months after injury ] [ Designated as safety issue: No ]
    The BVMT-R is a measure of visuospatial memory. Six equivalent, alternate stimulus forms consist of six geometric figures printed in a 2 x 3 array on separate pages. In three Learning Trials, the subject views the stimulus page for 10 seconds and is asked to draw as many of the figures as possible in their correct location. A Delayed Recall Trial is administered after a 25-minute delay. Last, a Recognition Trial, in which the respondent is asked to identify which of 12 figures were included among the original geometric figures, is administered. Scoring of the immediate and delayed recall are based on the accuracy of the drawings and the location of the figures. For each figure, one point is awarded to each satisfactory domain resulting in a maximum of 12-points per trial.

  • Symbol Digit Modalities Test - Oral Score [ Time Frame: 3 months after injury ] [ Designated as safety issue: No ]
    The SDMT is a measure of divided attention, visual scanning and motor speed. This measure involves a coding key consisting of 9 abstract symbols, each paired with a number ranging from 1 to 9. The subject is required to scan the key and write down the number corresponding to each symbol as fast as possible. The number of correct substitution within 90 seconds is recorded. In the written version of the test the subject fills in the numbers that correspond to the symbols. In the oral version the examiner records the numbers spoken by the subject. The score is the number of correctly coded items from 0-110 in 90 seconds. A higher score indicates better performance.

  • Symbol Digit Modalities Test - Written Score [ Time Frame: 3 months after injury ] [ Designated as safety issue: No ]
    The SDMT is a measure of divided attention, visual scanning and motor speed. This measure involves a coding key consisting of 9 abstract symbols, each paired with a number ranging from 1 to 9. The subject is required to scan the key and write down the number corresponding to each symbol as fast as possible. The number of correct substitution within 90 seconds is recorded. In the written version of the test the subject fills in the numbers that correspond to the symbols. In the oral version the examiner records the numbers spoken by the subject. The score is the number of correctly coded items from 0-110 in 90 seconds. A higher score indicates better performance.


Enrollment: 52
Study Start Date: February 2010
Study Completion Date: June 2015
Primary Completion Date: March 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: MTBI subjects randomized to drug

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
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.
Other Name: Lipitor®
Placebo Comparator: MTBI subjects randomized to placebo

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
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.

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years to 50 Years   (Adult)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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
  • exclusions related to atorvastatin, including currently taking any statin drug (atorvastatin, simvastatin, rosuvastatin, pravastatin, lovastatin, fluvastatin), no longer taking a statin drug but history of use within the last six months, previously taking any statin drug at any time but now discontinued due to side effects, taking any medication with known interactions with atorvastatin (cyclosporine, fibric acid derivative, erythromycin, clarithromycin, combination of ritonavir plus saquinavir or lopinavir, niacin in doses exceeding multivitamin dosage, or azole antifungals), active liver disease, history of unexplained persistent elevation of serum transaminases, and hypersensitivity to any component of atorvastatin.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01013870

Locations
United States, Texas
Baylor College of Medicine/Ben Taub General Hospital
Houston, Texas, United States, 77030
University of Texas Health Science Center at Houston/Memorial Hermann Hospital
Houston, Texas, United States, 77030
Sponsors and Collaborators
Baylor College of Medicine
The University of Texas Health Science Center, Houston
Investigators
Principal Investigator: Claudia S Robertson, MD Baylor College of Medicine
  More Information

Responsible Party: Claudia Sue Robertson, Professor, Department of Neurosurgery, Baylor College of Medicine
ClinicalTrials.gov Identifier: NCT01013870     History of Changes
Other Study ID Numbers: W81XWH-08-2-0132 
Study First Received: November 13, 2009
Results First Received: August 3, 2016
Last Updated: September 27, 2016
Health Authority: United States: Institutional Review Board
Individual Participant Data  
Plan to Share IPD: Yes
Plan Description: Data has been shared through the TED metadataset (https://tbiendpoints.ucsf.edu/ted-metadataset) and plans are to contribute the data to FITBIR as a legacy database.

Keywords provided by Baylor College of Medicine:
mild traumatic brain injury
post-concussion syndrome
acute stress disorder
post-traumatic stress disorder
atorvastatin

Additional relevant MeSH terms:
Wounds and Injuries
Brain Injuries
Stress Disorders, Traumatic
Stress Disorders, Post-Traumatic
Brain Concussion
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Craniocerebral Trauma
Trauma, Nervous System
Trauma and Stressor Related Disorders
Mental Disorders
Head Injuries, Closed
Wounds, Nonpenetrating
Atorvastatin Calcium
Neuroprotective Agents
Anticholesteremic Agents
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Lipid Regulating Agents
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Enzyme Inhibitors
Protective Agents
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on December 02, 2016