Working... Menu

Buspirone for the Treatment of Traumatic Brain Injury (TBI) Irritability and Aggression

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT01821690
Recruitment Status : Recruiting
First Posted : April 1, 2013
Last Update Posted : November 14, 2018
Information provided by (Responsible Party):
Flora Hammond, Indiana University

Brief Summary:
The purpose of this study is to improve behavior control displayed by persons with traumatic brain injury by assessing effectiveness of treatments for post-TBI irritability and aggression.

Condition or disease Intervention/treatment Phase
Traumatic Brain Injury Drug: Buspirone Drug: Placebo Not Applicable

Detailed Description:

PURPOSE OF PROJECT: To study the effect expressed by persons with TBI through assessment of buspirone effectiveness for post-traumatic irritability and aggression and development of an irritability/aggression impact measure.

SUMMARY OF PROJECT: It is anticipated that 74 subjects with 74 corresponding subject observers will be recruited for the treatment study. Subjects will be recruited from community and self-referrals.

Interested potential participants will be scheduled for an in-person screening visit. Subjects who consent and qualify will be randomized in a 1:1 ratio, buspirone or placebo. Stratification to randomization group will occur based on the presence of major or minor depression (defined by PHQ-9 total score >5). Randomized subjects will receive active treatment or placebo. There will be 4 clinic visits. Visits will occur at baseline, for consenting and screening, day 35, day 63 and day 91. At all 4 clinic visits, both the subject and the observer will be given questionnaires regarding the subject's behavior and mood. Day 91 ends the period of the randomized clinical trial phase of the study and the subjects will begin the 1 month continuation phase of the study in which all participants receive active buspirone.

The following questionnaires will be used as measures of irritability and aggression for the subject and the observer: Neuropsychiatric Inventory (NPI & NPI-Distress), Aggression & Irritability Impact Measure (AIIM) and Global Impression of Change.

The following questionnaires will be dispensed to the subject only: TBI-Quality of Life-Anger, Personal Health Questionnaire (PHQ-9), Generalized Anxiety Disorder (GAD-7), PTSD Checklist Civilian (PCL-C), and Glasgow Outcome Scale Extended (GOS-E) The Investigator will complete the Clinical Global Impression of change at Visits 1, 2, 3, and 4. History and Physical Exam, creatinine level (kidney function) and liver function tests will be obtained for eligibility. Serum pregnancy tests will be drawn at screening for females of childbearing potential.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 74 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Brain Research in Aggression and Irritability Network (BRAIN): Building Evidence-Based Approaches to Managing Traumatic Brain Injury
Study Start Date : May 2013
Estimated Primary Completion Date : December 2020
Estimated Study Completion Date : December 2020

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: Buspirone Treatment
starting at 15 mg/day and ending at 60 mg/day as prescribed
Drug: Buspirone
Buspirone/placebo will be given in increasing increments of 15 mg as needed. Subjects will start with 15 mg on day one and end with 60 mg on day 91 or placebo equivalent. Dose is titrated based on treatment response.
Other Name: Buspar

Placebo Comparator: Buspirone Placebo
placebo tablets as prescribed
Drug: Placebo
The placebo tablets taste and look identical to buspirone.

Primary Outcome Measures :
  1. Neuropsychiatric Inventory-Irritability Domain [ Time Frame: Day 91 ]
    A self-report measure of irritability

Secondary Outcome Measures :
  1. Neuropsychiatric Inventory-Aggression Domain [ Time Frame: Day 91 ]
    A self-report measure of aggression

  2. Neuropsychiatric Inventory-Distress Irritability Domain [ Time Frame: Day 91 ]
    A self-report measure of the distress caused by irritability

  3. Neuropsychiatric Inventory-Distress Aggression Domain [ Time Frame: Day 91 ]
    A self-report measure of the distress caused by aggression

  4. St. Andrews-Swansea Neurobehavioural Outcome Scale [ Time Frame: Day 91 ]
    A self-report measure of overall neurobehavioral function

  5. Personal Health Questionnaire [ Time Frame: Day 91 ]
    A measure of depression that maps on to DSM criteria for depression

  6. Traumatic Brain Injury-Quality of Life Anger [ Time Frame: Day 91 ]
    A self-report measure of overall impact of anger on quality of life

  7. Global Impressions of Change [ Time Frame: Day 91 ]
    A self-report measure of overall change

  8. Clinical Global Impressions [ Time Frame: Day 91 ]
    Clinician rating of overall change

  9. Aggression and Irritability Impact Measure [ Time Frame: 91 Day ]
    A self-report measure of overall impact of irritability on life participation

  10. Generalized Anxiety Disorder [ Time Frame: 91 day ]
    A self-report measure of anxiety

Information from the National Library of Medicine

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, Learn About Clinical Studies.

Layout table for eligibility information
Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Closed head injury (impaired brain function resulting from externally inflicted trauma without penetrating injury as defined below) at least 6 months prior to enrollment
  • Irritability that is either new or worse than level of irritability before the traumatic brain injury, by report of observer or person with TBI
  • Age at time of enrollment: 18 to 70 years
  • Voluntary informed consent of patient and observer
  • Subject and observer willing to comply with the protocol
  • Observer-rated NPI Irritability Domain score 6 or greater to include only moderate-severe irritability
  • Medically and neurologically stable during the month prior to enrollment.
  • If taking antidepressant, anxiolytic, hypnotic, or stimulant medications, no change anticipated in these medications during the month prior to enrollment
  • No change in therapies or medications planned during the 91-day participation
  • No surgeries planned during the 91-day participation
  • Vision, hearing, speech, motor function, and comprehension sufficient for compliance with all testing procedures and assessments
  • Observer (e.g.: family member, close friend, employer) with whom subject interacts sufficiently to observe occurrences of irritability. The observer interacts with the participant for a period long enough and of a nature to be able to judge the participant's irritability. The interactions would need to be adequate to judge observer distress over the irritability, severity of irritability and frequency of irritability on the following scale: < once weekly; once per week; several times per week, but not every day; essentially continuous.

Exclusion Criteria:

  • Potential subject without a reliable observer
  • Penetrating head injury as defined by head injury due to gunshot, projectile or foreign object
  • Injury < 6 months prior to enrollment
  • Ingestion of buspirone during the month prior to enrollment
  • Inability to interact sufficiently for communication with caregiver
  • History of schizophrenia or psychosis or bipolar disorder
  • Diagnosis of progressive or additional neurologic disease
  • Clinical signs of active infection

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01821690

Layout table for location contacts
Contact: Rebecca Runkel, MHA (317) 329-2217
Contact: Kelsey Hurm, MA (317) 329-2944

Layout table for location information
United States, Indiana
Indiana University and Rehabilitation Hospital of Indiana Recruiting
Indianapolis, Indiana, United States, 46254
Contact: Flora Hammond, MD    317-329-2106   
Contact: Rebecca Runkel, MHA    317-329-2217   
Principal Investigator: Flora Hammond, MD         
Sponsors and Collaborators
Indiana University
Layout table for investigator information
Principal Investigator: Flora Hammond, MD Indiana University/Rehabilitation Hospital of Indiana

Additional Information:
Layout table for additonal information
Responsible Party: Flora Hammond, Covalt Professor and Chair, Physical Medicine and Rehabilitation, Indiana University School of Medicine Chief of Medical Affairs, Rehabilitation Hospital of Indiana, Indiana University Identifier: NCT01821690     History of Changes
Other Study ID Numbers: 1210009885
CFDA #: 84.133A-120035 ( Other Grant/Funding Number: National Institute on Disability and Rehabilitation Research )
First Posted: April 1, 2013    Key Record Dates
Last Update Posted: November 14, 2018
Last Verified: November 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided
Plan Description: De-identified data will be available upon request 24 months after completion of the project. Data requests should be submitted to the principal investigator.

Keywords provided by Flora Hammond, Indiana University:
Traumatic Brain Injury

Additional relevant MeSH terms:
Layout table for MeSH terms
Wounds and Injuries
Brain Injuries
Brain Injuries, Traumatic
Craniocerebral Trauma
Trauma, Nervous System
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Behavioral Symptoms
Anti-Anxiety Agents
Tranquilizing Agents
Central Nervous System Depressants
Physiological Effects of Drugs
Psychotropic Drugs
Serotonin Receptor Agonists
Serotonin Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action