Treatment Strategy to Prevent Mood Disorders Following Traumatic Brain Injury

Baylor College of Medicine

Status and phase: Completed; Phase 3; Phase 2

Conditions: Traumatic Brain Injury

Treatments: Drug: Sertraline; Drug: Placebo

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT00704379

1R01NS055827-01A2 (U.S. NIH Grant/Contract)

R01NS055827

Details and patient eligibility

About

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.

Full 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.

Enrollment: 94 patients

Sex: All

Ages: 18 to 85 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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94 participants in 2 patient groups, including a placebo group

Placebo

Placebo Comparator group

Description:

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

Treatment:

Drug: Placebo

Sertraline

Experimental group

Description:

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.

Treatment:

Drug: Sertraline