Mission Connect Mild Traumatic Brain Injury (TBI) Integrated Clinical Protocol - Full Text View

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
Mild 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:

MedlinePlus related topics: Post-Traumatic Stress Disorder Traumatic Brain Injury

Drug Information available for: Atorvastatin calcium

U.S. FDA Resources

Further study details as provided by Baylor College of Medicine:

Primary Outcome Measures:

Subjects with mild traumatic brain injury (MTBI) treated with atorvastatin for 7 days after MTBI will show a significant improvement in outcome, as measured by the Rivermead Post-Concussion Symptoms Questionnaire, administered at 3 months after injury. [ Time Frame: 3 months after injury ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

MTBI subjects treated with atorvastatin for 7 days after mild TBI will show fewer symptoms of PCS and PTSD at 3 months post injury than those receiving placebo. [ Time Frame: 3 months ] [ Designated as safety issue: No ]
MTBI subjects treated with atorvastatin for 7 days after mild TBI will show greater cognitive recovery and higher functional outcome than those receiving placebo. [ Time Frame: 3 months after injury ] [ Designated as safety issue: No ]
MTBI subjects treated with atorvastatin for 7 days after mild TBI will show better preservation of whole brain volumes and reduced white matter abnormalities at 3 months post-injury than placebo treated subjects. [ Time Frame: 3 months after injury ] [ Designated as safety issue: No ]
There will be no significant difference in liver function tests between the subjects treated with atorvastatin for 7 days and those receiving placebo. [ Time Frame: 1 week, 1 month, and 3 months after injury ] [ Designated as safety issue: Yes ]
There will be no significant difference in clinical findings of liver dysfunction (jaundice, discolored urine, fatigue, or unexplained fever) or in other reported symptoms between subjects treated with atorvastatin for 7 days and those receiving placebo. [ Time Frame: 1 week, 1 month, 3 months after injury ] [ Designated as safety issue: Yes ]

Estimated Enrollment:	200
Study Start Date:	February 2010
Estimated Study Completion Date:	July 2013
Estimated Primary Completion Date:	January 2013 (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.

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
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

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

Contacts

Contact: Emmy R Miller, PhD, RN	713 873-2793	emmym@bcm.tmc.edu
Contact: Melisa Frisby, MSN, RN	713 798-6483	frisby@bmc.tmc.edu

Locations

United States, Texas
Baylor College of Medicine/Ben Taub General Hospital	Recruiting
Houston, Texas, United States, 77030
Contact: Claudia S Robertson, MD 713-873-2793 claudiar@bcm.tmc.edu
Principal Investigator: Claudia R Robertson, MD
University of Texas Health Science Center at Houston/Memorial Hermann Hospital	Recruiting
Houston, Texas, United States, 77030
Contact: James J McCarthy, MD 713-500-5001 James.J.McCarthy@uth.tmc.edu
Principal Investigator: James J McCarthy, MD

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

No publications provided

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
Last Updated:	July 30, 2012
Health Authority:	United States: Institutional Review Board

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:

Stress Disorders, Post-Traumatic
Stress Disorders, Traumatic
Brain Injuries
Anxiety Disorders
Mental Disorders
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Craniocerebral Trauma
Trauma, Nervous System
Wounds and Injuries
Atorvastatin
Neuroprotective Agents

Hydroxymethylglutaryl-CoA Reductase Inhibitors
Anticholesteremic Agents
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Enzyme Inhibitors
Lipid Regulating Agents
Therapeutic Uses
Protective Agents
Physiological Effects of Drugs
Central Nervous System Agents

ClinicalTrials.gov processed this record on June 18, 2013