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

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2015 by Indiana University
Information provided by (Responsible Party):
Flora Hammond, Indiana University
ClinicalTrials.gov Identifier:
First received: March 27, 2013
Last updated: August 30, 2015
Last verified: August 2015
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 Intervention
Traumatic Brain Injury
Drug: Buspirone
Drug: Placebo

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, 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

Resource links provided by NLM:

Further study details as provided by Indiana University:

Primary Outcome Measures:
  • Neuropsychiatric Inventory-Irritability Domain [ Time Frame: Day 91 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Neuropsychiatric Inventory-Aggression Domain [ Time Frame: Day 91 ] [ Designated as safety issue: No ]
  • Neuropsychiatric Inventory-Distress Irritability Domain [ Time Frame: Day 91 ] [ Designated as safety issue: No ]
  • Neuropsychiatric Inventory-Distress Aggression Domain [ Time Frame: Day 91 ] [ Designated as safety issue: No ]
  • St. Andrews-Swansea Neurobehavioural Outcome Scale [ Time Frame: Day 91 ] [ Designated as safety issue: No ]
  • Personal Health Questionnaire [ Time Frame: Day 91 ] [ Designated as safety issue: No ]
  • Traumatic Brain Injury-Quality of Life Anger [ Time Frame: Day 91 ] [ Designated as safety issue: Yes ]
  • Global Impressions of Change [ Time Frame: Day 91 ] [ Designated as safety issue: No ]
  • Clinical Global Impressions [ Time Frame: Day 91 ] [ Designated as safety issue: No ]
  • Aggression and Irritability Impact Measure [ Time Frame: 91 Day ] [ Designated as safety issue: No ]
  • Generalized Anxiety Disorder [ Time Frame: 91 day ] [ Designated as safety issue: No ]

Estimated Enrollment: 74
Study Start Date: May 2013
Estimated Study Completion Date: December 2017
Estimated Primary Completion Date: September 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.


Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
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
  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: NCT01821690

Contact: Rebecca Runkel, MHA (317) 329-2217 becky.runkel@rhin.com
Contact: Kara Jodry, BA (317) 329-2529 kara.jodry@rhin.com

United States, Indiana
Indiana University and Rehabilitation Hospital of Indiana Recruiting
Indianapolis, Indiana, United States, 46254
Contact: Flora Hammond, MD    317-329-2106    flora.hammond@rhin.com   
Contact: Rebecca Runkel, MHA    317-329-2217    becky.runkel@rhin.com   
Principal Investigator: Flora Hammond, MD         
Sponsors and Collaborators
Indiana University
Principal Investigator: Flora Hammond, MD Indiana University/Rehabilitation Hospital of Indiana
  More Information

Additional 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
ClinicalTrials.gov Identifier: NCT01821690     History of Changes
Other Study ID Numbers: 1210009885  CFDA #: 84.133A-120035 
Study First Received: March 27, 2013
Last Updated: August 30, 2015
Health Authority: United States: Institutional Review Board

Keywords provided by Indiana University:
Traumatic Brain Injury

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

ClinicalTrials.gov processed this record on May 22, 2016