Carbamazepine for the Treatment of Chronic Post-Traumatic Brain Injury Irritability and Aggression

NCT00621751 | Completed Results DMC

• 2 other identifiers: 12-07-02AH133A20016
• Study Type: interventional
• Target: 70
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to determine if carbamazepine reduces irritability and aggression among individuals with traumatic brain injury

Conditions

Traumatic Brain Injury

Keywords

Brain Injury; Irritability; Aggression

Outcome Measures

Primary Outcomes (1)

• Neuropsychiatric Inventory Irritability-Aggression Domains Composite Measure -- Observer

  Neuropsychiatry Inventory-Irritability (NPI-I) \& Aggression domains (NPI-A): NPI is a 40-item assessment of 12 behavioral domains (NPI-I \& NPI-A domains used in this study). The most problematic aspect of each domain is graded for severity (1=mild, to 3=severe) and frequency (1-4 with 4 representing highest frequency); the domain scores (0-12) are the product of severity and frequency. To best reflect treatment target intent and meet parametric statistical method criteria, the primary outcome was a composite measure of observer-rated NPI-I \& -A domains transformed to a Rasch logit scale running from 0 (best) to 100 (worse) units (i.e., observer-rated NPI-I/A Rasch construct scores). Mean day-42 observer-rated NPI-I/A Rasch construct scores were compared between placebo vs. carbamazepine using ANCOVA with baseline score as covariate.

  42 days

Secondary Outcomes (6)

• Proportion of Participants With Minimal Clinically Important Difference -- Observer Rating

  42-day

• Global Impression of Change -- Observer

  42 days

• Neuropsychiatric Inventory Irritability-Aggression Domains Composite Measure Completed by Participant [Time Frame: 42 Days]

  Day 42

• Proportion of Participants With Minimal Clinically Important Difference (MCID) -- Participant

  Day-42

• Clinicians Global Impression of Change

  42 days

Study Arms (2)

Carbamazepine

EXPERIMENTAL

Carbamazepine 800 mg daily

Drug: Carbamazepine

Placebo

PLACEBO COMPARATOR

Placebo

Drug: Placebo

Interventions

Carbamazepine DRUG

800 mg daily

Also known as: Tegretol

Carbamazepine

Placebo DRUG

Placebo

Placebo

Eligibility Criteria

• Age: 16 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Closed head injury (defined as impaired brain function resulting from externally inflicted trauma without penetrating injury) at least 6 months prior to enrollment
• Age at time of enrollment: 16 to 75 years
• Voluntary informed consent of patient and informant
• Subject and informant willing to comply with the protocol
• Informant-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 42-day participation No surgeries planned during the 42-day participation Vision, hearing, speech, motor function, and comprehension sufficient for compliance with all testing procedures and assessments
• Informant (e.g. family member or close friend) with daily interaction in order to observe occurrences of irritability

You may not qualify if:

• Potential subject without a reliable informant
• Penetrating head injury
• Injury \< 6 months prior to enrollment
• Ingestion of carbamazepine during the month prior to enrollment
• Inability to interact sufficiently for communication with caregiver
• Acute and rehabilitation records unavailable or incomplete
• Diagnostic and Statistical Manual of Mental Disorders-IV (DSM-IV) diagnosis of schizophrenia or psychosis
• Diagnosis of progressive or additional neurologic disease
• Clinical signs of active infection
• Creatinine clearance \<60 mL/min
• Liver function tests \> 2x normal values
• Pregnancy; lactating females; sexually active females who do not agree to use birth control
• Hormonal birth control as only means of birth control if sexually active and of child bearing age potential due to carbamazepine effect of lowering hormone levels, and potentially effectiveness
• Concurrent use of the following medicines due to potential for drug interaction: macrolides, rifabutin, doxycycline, nicoumalone, warfarin, fluoxetine, fluvoxamine, viloxazine, nefazodone, tricyclic and tetracyclic antidepressants, clobazam, clonazepam, lamotrigine, phenytoin, sodium valproate, tigabine and topiramate, phenobarbitone, primidone, chloroquine and mefloquine, antipsychotics, indinavir, nelfinavir, saquinavir, ritonavir, diltiazem, verapamil, felodipine, isradipine, nicardipine, nifedipine, cimetidine, cyclosporins, corticosteroids, gestrinone and toremifene, danazol, tibolone
• Suicidal ideation

Sponsors & Collaborators

• Wake Forest University Health Sciences: lead
• U.S. Department of Education: collaborator

Study Sites (1)

Carolinas Rehabilitation

Charlotte, North Carolina, 28203, United States

Location

Related Publications (4)

• Azouvi P, Jokic C, Attal N, Denys P, Markabi S, Bussel B. Carbamazepine in agitation and aggressive behaviour following severe closed-head injury: results of an open trial. Brain Inj. 1999 Oct;13(10):797-804. doi: 10.1080/026990599121188.

  PMID: 10576463 BACKGROUND

• Chatham-Showalter PE. Carbamazepine for combativeness in acute traumatic brain injury. J Neuropsychiatry Clin Neurosci. 1996 Winter;8(1):96-9. doi: 10.1176/jnp.8.1.96.

  PMID: 8845710 BACKGROUND

• Lewin J, Sumners D. Successful treatment of episodic dyscontrol with carbamazepine. Br J Psychiatry. 1992 Aug;161:261-2. doi: 10.1192/bjp.161.2.261.

  PMID: 1521112 BACKGROUND

• Wroblewski BA, Joseph AB, Kupfer J, Kalliel K. Effectiveness of valproic acid on destructive and aggressive behaviours in patients with acquired brain injury. Brain Inj. 1997 Jan;11(1):37-47. doi: 10.1080/026990597123791.

  PMID: 9012550 BACKGROUND

Related Links

• Carolinas Rehabilitation

MeSH Terms

Conditions

Brain Injuries, Traumatic; Brain Injuries; Aggression

Interventions

Carbamazepine

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Dibenzazepines; Heterocyclic Compounds, 3-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Flora Hammond, MD
• Organization: Atrium Health; Currently at Indiana University School of Medicine

flora.hammond@rhin.com

317-292-6781

Study Officials

• Flora M Hammond, MD

  Wake Forest University Health Sciences

  PRINCIPAL INVESTIGATOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 13, 2008
• First Posted: February 22, 2008
• Study Start: February 1, 2008
• Primary Completion: September 1, 2013
• Study Completion: October 1, 2013
• Last Updated: April 22, 2022
• Results First Posted: August 19, 2021

Record last verified: 2021-08

Locations

US (1)