Now Available for Public Comment: Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

Treatment Strategy to Prevent Mood Disorders Following Traumatic Brain Injury

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Ricardo Jorge, MD, Baylor College of Medicine
ClinicalTrials.gov Identifier:
NCT00704379
First received: June 20, 2008
Last updated: July 31, 2014
Last verified: July 2014
  Purpose

The purpose of this study is to examine the efficacy of sertraline to prevent the onset of mood and anxiety disorders during the first six months after traumatic brain injury.


Condition Intervention Phase
Traumatic Brain Injury
Drug: Placebo
Drug: Sertraline
Phase 2
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: Treatment Strategy to Prevent Mood Disorders Following Traumatic Brain Injury

Resource links provided by NLM:


Further study details as provided by Baylor College of Medicine:

Primary Outcome Measures:
  • Time to onset of Diagnostic and Statistical Manual IV defined mood and anxiety disorders; Total Community Integration Questionnaire scores at baseline, 3, and 6 months; Executive function composite will measure cognitive impairment. [ Time Frame: 6 Months following traumatic brain injury ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Overt Aggression Scale-Modified total score will quantify the degree of aggressive behavior. [ Time Frame: 6 Months following traumatic brain injury ] [ Designated as safety issue: No ]
  • Diagnostic and Statistical Manual IV defined Personality change due to TBI (disinhibited, aggressive or combined types). [ Time Frame: 6 Months following traumatic brain injury ] [ Designated as safety issue: No ]
  • Iowa Gambling Test score will measure the quality of decision making. [ Time Frame: 6 Months following traumatic brain injury ] [ Designated as safety issue: No ]
  • Memory function composite will measure cognitive impairment. [ Time Frame: 6 Months following traumatic brain injury ] [ Designated as safety issue: No ]
  • Neuroimaging variables [ Time Frame: 6 Months following traumatic brain injury ] [ Designated as safety issue: No ]
  • Social Functioning Examination scores will measure the degree of satisfaction with social functioning at one year follow-up. [ Time Frame: 6 Months following traumatic brain injury ] [ Designated as safety issue: No ]
  • Fractional anisotropy of frontal white matter will measure white matter integrity. [ Time Frame: 6 Months following traumatic brain injury ] [ Designated as safety issue: No ]

Enrollment: 94
Study Start Date: June 2008
Study Completion Date: April 2014
Primary Completion Date: April 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Placebo
Placebo will be given in a double blind fashion via an equal number of tablets (identical to the sertraline tablets) administered once daily.
Drug: Placebo
an inactive substance
Experimental: Sertraline
Sertraline will be given in a double blind fashion via tablets administered once daily. Once stabilized in the targeted dosage (100 mg per day), sertraline serum levels will be monitored twice during the course of the intervention.
Drug: Sertraline
Sertraline and placebo will be given in a double blind fashion via an equal number of identical tablets administered once daily. Once stabilized in the targeted dosage (100 mg per day), sertraline serum levels will be monitored twice during the course of the intervention. Blood samples will be obtained randomly, one during the first and one during the second trimesters of the protocol.
Other Name: Zoloft

Detailed Description:

Traumatic brain injury (TBI) is a leading cause of death and disability among young adults. Mood disorders are the most frequent psychiatric complication of TBI, and have a large impact on family functioning, interpersonal relationships, and ability to return to work or school. Furthermore, a significant proportion of these disorders will progress to more chronic and treatment refractory forms. In spite of their clinical relevance, mood and anxiety disorders remain largely unrecognized and not adequately treated, contributing to greater disability and decreased participation in the aftermath of TBI.

The goals of this study are to learn more about how people recover from brain injury and to evaluate the effect of sertraline (also known as Zoloft) compared to placebo (an inactive substance) in preventing the occurrence of emotional and behavioral problems—such as depression, lack of motivation, anxiety, irritability or aggressive outbursts—following TBI.

In the study, a group of 104 participants with TBI—recruited immediately after resolution of posttraumatic amnesia—will be randomly assigned to receive six months of double-blind treatment with sertraline or placebo.

This study will determine how these emotional and behavioral problems influence thinking, physical recovery, and return to a productive life six months after brain injury. Researchers will also determine if certain brain changes can predict the occurrence of behavioral problems and if treatment with sertraline can prevent them. Additionally, the researchers will examine the effect of sertraline on frequent post-TBI behavioral disorders such as aggression, impulsivity, poor decision making and apathetic symptoms.

Magnetic resonance imaging (MRI)-based volumetry and diffusion tensor imaging will be used to examine the structural correlates of mood and anxiety disorders and to evaluate them as biological predictors of treatment response and community reintegration. The researchers hypothesize that early preventive treatment with sertraline will reduce mood and behavioral symptoms, prevent the occurrence of structural and functional brain changes associated with the onset of mood disorders, increase access to and participation in rehabilitation programs for TBI, and, consequently, improve psychosocial outcome.

  Eligibility

Ages Eligible for Study:   18 Years to 85 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age 18 years or over.
  • Meeting the Center for Disease Control (CDC) criteria for TBI.
  • Mild, Moderate, or Severe TBI as categorized by initial Glasgow Coma Scale (GCS) scores 13 to 15, 9 to 12, or 3 to 8, respectively.
  • Complete recovery from Post Traumatic Amnesia (PTA) within 4 weeks of the traumatic episode.

Exclusion Criteria:

  • Penetrating head injuries.
  • Clinical or neuro-radiological evidence of associate spinal cord injury.
  • Patients with severe comprehension deficits (i.e., those who are not able to complete part II of the Token Test) that precludes a thorough neuropsychiatric evaluation.
  • Presence of Diagnostic and Statistical Manual IV defined mood, anxiety or psychotic disorder at the time of enrollment to the study. However, patients with a history of alcohol abuse or alcohol dependence during the year preceding TBI will be included in the study.
  • Patients who were taking antidepressants at the time of TBI or during a six month period prior to the traumatic event.
  • Patients who have failed an adequate previous trial with sertraline or had side effects that prompted the discontinuation of this medication.
  • Pregnant women or women that plan to become pregnant during the period of the study.
  • Severe complicating illness such as neoplastic disease or uncompensated heart, renal or liver failure.
  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: NCT00704379

Locations
United States, Texas
Baylor College of Medicine
Houston, Texas, United States, 77030-4211
Sponsors and Collaborators
Baylor College of Medicine
Investigators
Principal Investigator: Ricardo E. Jorge, MD Baylor College of Medicine
  More Information

Publications:
Silver, J.M., R.E. Hales, and S.C. Yudofsky, Psychopharmacology of depression in neurologic disorders. J Clin Psychiatry, 1990. 51 Suppl: p. 33-9.

Responsible Party: Ricardo Jorge, MD, Professor, Baylor College of Medicine
ClinicalTrials.gov Identifier: NCT00704379     History of Changes
Other Study ID Numbers: R01NS055827, 1 R01 NS055827-01A2
Study First Received: June 20, 2008
Last Updated: July 31, 2014
Health Authority: United States: Federal Government

Keywords provided by Baylor College of Medicine:
traumatic brain injury
TBI
mood disorders
anxiety disorders
community reintegration
executive function
sertraline
diffusion tensor imaging

Additional relevant MeSH terms:
Brain Injuries
Mood Disorders
Brain Diseases
Central Nervous System Diseases
Craniocerebral Trauma
Mental Disorders
Nervous System Diseases
Trauma, Nervous System
Wounds and Injuries
Sertraline
Antidepressive Agents
Central Nervous System Agents
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Neurotransmitter Uptake Inhibitors
Pharmacologic Actions
Physiological Effects of Drugs
Psychotropic Drugs
Serotonin Agents
Serotonin Uptake Inhibitors
Therapeutic Uses

ClinicalTrials.gov processed this record on November 27, 2014