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

NCT01821690 | Completed Phase 4 Results DMC FDA Drug

• 2 other identifiers: 1210009885CFDA #: 84.133A-120035
• Study Type: interventional
• Target: 81
• Locations: 1 country
• Sites: 1

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.

Conditions

Traumatic Brain Injury

Keywords

Traumatic Brain Injury; Buspirone; Behavior; Irritability; Aggression

Outcome Measures

Primary Outcomes (1)

• Neuropsychiatric Inventory-Irritability Domain - Observer-rated Proportion Improved ≥ 3 Points Baseline to Day-91

  Neuropsychiatric Inventory (NPI) is a 40-item instrument evaluating 12 behavioral domains with prior use in TBI. NPI-Irritability domain (NPI-I) encompasses temper outbursts, mood fluctuations, abrupt anger, impatience, irritable disposition, and argumentative behavior. Assessment involves identifying if these behaviors are present and then scoring the most concerning manifestation on severity (1=mild to 3=severe) and frequency (1-4 scale, higher=greater occurrence). Domain totals (0-12 range) represent the product of severity and frequency ratings for the predominant symptom.

  Day 91

Secondary Outcomes (9)

• Neuropsychiatric Inventory-Aggression Domain - Observer-rated Proportion Improved ≥ 3 Points Baseline to Day-91

  Day 91

• Neuropsychiatric Inventory-Distress Irritability Domain - Observer-rated

  Day 91

• Neuropsychiatric Inventory-Distress Aggression Domain - Observer Rated

  Day 91

• St. Andrews-Swansea Neurobehavioural Outcome Scale - Observer-rated

  Day 91

• Global Impressions of Change - Observer-rated

  Day 91

Study Arms (2)

Buspirone Treatment

EXPERIMENTAL

starting at 15 mg/day and ending at 60 mg/day as prescribed

Drug: Buspirone

Buspirone Placebo

PLACEBO COMPARATOR

placebo tablets as prescribed

Drug: Placebo

Interventions

Buspirone DRUG

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.

Also known as: Buspar

Buspirone Treatment

Placebo DRUG

The placebo tablets taste and look identical to buspirone.

Also known as: Inactive

Buspirone Placebo

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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
• Diagnosis of progressive or additional neurologic disease
• Clinical signs of active infection

Sponsors & Collaborators

• Indiana University: lead

Study Sites (1)

Indiana University and Rehabilitation Hospital of Indiana

Indianapolis, Indiana, 46254, United States

Location

Related Links

• Rehabilitation Hospital of Indiana
• Indiana University School of Medicine

MeSH Terms

Conditions

Brain Injuries, Traumatic; Behavior; Aggression

Interventions

Buspirone

Condition Hierarchy (Ancestors)

Brain Injuries; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Craniocerebral Trauma; Trauma, Nervous System; Wounds and Injuries; Aberrant Motor Behavior in Dementia; Behavioral Symptoms; Social Behavior

Intervention Hierarchy (Ancestors)

Spiro Compounds; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrimidines; Polycyclic Compounds

Limitations and Caveats

No technical problems to report. Study recruitment took place over 12 years until the a priori sample size was achieved.

Results Point of Contact

• Title: Flora Hammond
• Organization: Indiana University School of Medicine

hammondf@iu.edu

317-329-2000

Study Officials

• Flora Hammond, MD

  Indiana University/Rehabilitation Hospital of Indiana

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Covalt Professor and Chair, Physical Medicine and Rehabilitation, Indiana University School of Medicine Chief of Medical Affairs, Rehabilitation Hospital of Indiana

Study Record Dates

• First Submitted: March 27, 2013
• First Posted: April 1, 2013
• Study Start: May 15, 2013
• Primary Completion: September 26, 2025
• Study Completion: September 26, 2025
• Last Updated: February 24, 2026
• Results First Posted: February 24, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)