Official Title: “Treatment Strategy to Prevent Mood Disorders Following Traumatic Brain Injury”

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.

Study Type: Interventional

Study Design: Prevention, Randomized, Double Blind (Subject, Caregiver, Outcomes Assessor), Parallel Assignment, Efficacy Study

Study Primary Completion Date: January 2013

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.

Intervention(s) in this Clinical Trial

• Drug: Placebo
  • an inactive substance
• 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.

Arms, Groups and Cohorts in this Clinical Trial

• Placebo Comparator: A
  • Placebo will be given in a double blind fashion via an equal number of tablets (identical to the sertraline tablets) administered once daily.
• Experimental: B
  • 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.

Primary Measures

• Time to onset of DSM-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
    Safety Issue?: No
• Fractional anisotropy of frontal white matter will measure white matter integrity.
  • Time Frame: 6 Months following traumatic brain injury
    Safety Issue?: No

Secondary Measures

• Overt Aggression Scale-Modified total score will quantify the degree of aggressive behavior.
  • Time Frame: 6 Months following traumatic brain injury
    Safety Issue?: No
• DSM-IV defined Personality change due to TBI (disinhibited, aggressive or combined types).
  • Time Frame: 6 Months following traumatic brain injury
    Safety Issue?: No
• Iowa Gambling Test score will measure the quality of decision making.
  • Time Frame: 6 Months following traumatic brain injury
    Safety Issue?: No
• Memory function composite will measure cognitive impairment.
  • Time Frame: 6 Months following traumatic brain injury
    Safety Issue?: No
• Neuroimaging variables
  • Time Frame: 6 Months following traumatic brain injury
    Safety Issue?: No
• SFE scores will measure the degree of satisfaction with social functioning at one year follow-up.
  • Time Frame: 6 Months following traumatic brain injury
    Safety Issue?: No

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 DSM-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.

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: 80 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: University of Iowa

Overall Clinical Trial Officials and Contacts

Ricardo E. Jorge, MD Principal Investigator Department of Psychiatry, UI Hospitals and Clinics  

Overall Contact: Stephanie A. Rosazza, BA 319-353-5807 stephanie-rosazza@uiowa.edu

Information obtained from ClinicalTrials.gov on July 02, 2009

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00704379

Study ID Number: R01NS055827

ClinicalTrials.gov Identifier: NCT00704379

Health Authority: United States: Federal Government