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

This study has been completed.
Sponsor:
Collaborator:
U.S. Department of Education
Information provided by (Responsible Party):
Flora Hammond, Carolinas Healthcare System
ClinicalTrials.gov Identifier:
NCT00621751
First received: February 13, 2008
Last updated: August 11, 2014
Last verified: August 2014
  Purpose

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


Condition Intervention
Traumatic Brain Injury
Drug: Carbamazepine
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: Carbamazepine for the Treatment of Chronic Post-Traumatic Brain Injury Irritability and Aggression: A 42-Day, Single-Site, Forced-Titration, Parallel Group, Randomized, Double-Blind, Placebo Controlled Trial

Resource links provided by NLM:


Further study details as provided by Carolinas Healthcare System:

Primary Outcome Measures:
  • Neuropsychiatric Inventory Irritability Domain (frequency and severity) completed by observer [ Time Frame: 42 days ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Neuropsychiatric Inventory Aggression Domain (frequency, severity, and caregiver distress) completed by the observer and person with brain injury [ Time Frame: 42 days ] [ Designated as safety issue: No ]
  • Neuropsychiatric Inventory Irritability Domain (caregiver distress) completed by the observer and the Neuropsychiatric Inventory Irritability Domain (frequency, severity and distress) completed by person with brain injury [ Time Frame: 42 days ] [ Designated as safety issue: No ]
  • Global Impression of Change [ Time Frame: 42 days ] [ Designated as safety issue: No ]
  • STAXI-2 by observer [ Time Frame: 42 days ] [ Designated as safety issue: No ]
  • STAXI-2 completed by person with brain injury [ Time Frame: 42 days ] [ Designated as safety issue: No ]
  • Clinicians Global Impression of Change [ Time Frame: 42 days ] [ Designated as safety issue: No ]
    Study physician's impression of change since study onset


Enrollment: 74
Study Start Date: February 2008
Study Completion Date: October 2013
Primary Completion Date: September 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: A
Carbamazepine 800 mg daily
Drug: Carbamazepine
800 mg daily
Other Name: Tegretol
Placebo Comparator: B
Placebo
Drug: Placebo
Placebo

Detailed Description:

It is anticipated that 74 subjects with 74 corresponding subject informants will be recruited at Carolinas Rehabilitation. Subjects will be recruited from the clinic at Carolinas Rehabilitation. Subjects will also be referred by psychiatrists at North Carolina Neuropsychiatry.

Subjects who consent and qualify will be randomized in a 1:1 ratio to Tegretol® or placebo. Stratification to randomization group will occur based on the presence of depression defined by a BDI-II score ≥ 13. Subjects randomized to active drug will be titrated up in dose, as tolerated, over a period of 3 weeks. Starting dose is 200mg twice daily to 200mg three times daily to 200mg, 2 tabs, twice daily. There will be 3 clinic visits. Visits will occur at baseline for consenting and screening, day 28, and day 42. Follow up phone calls will occur each week that the subject is not seen in the clinic until the end of the study. Follow up phone calls will assess for study medication compliance, adverse events and concomitant medication changes. Day 42 ends the period of the Randomized Clinical Trial phase of the study and the subjects will begin the 1 week of taper of Tegretol® at 400mg daily and then stop drug. A safety phone call will be made at day 49.

The following questionnaires will be used as measures of irritability for the subject and the informant: Neuropsychiatric Inventory (NPI), State Trait Anger Expression Inventory (STAXI-2), and Global Impression of Change. The following 3 questionnaires will be dispensed to the subject only: Beck Depression Inventory, Brief Symptom Inventory, and Fatigue Impact Scale. The Investigator will complete the Clinical Global Impression of change at Visits 2 and 3.

History and Physical Exam, hematology, chemistry, including renal and liver function studies will be obtained for safety and tolerability. Serum pregnancy tests will be drawn at screening for females of childbearing potential. Carbamazepine levels will be drawn at visits 2 and 3.

  Eligibility

Ages Eligible for Study:   16 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • Potential subject without a reliable informant
  • Penetrating head injury
  • Injury < 6 months prior to enrollment
  • Ingestion of CBZ during the month prior to enrollment
  • Inability to interact sufficiently for communication with caregiver
  • Acute and rehabilitation records unavailable or incomplete
  • 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 (Beta-HCG + females of child-bearing potential); 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 CBZ 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
  • Concurrent use of Monoamine Oxidase Inhibitors (MAOIs) or ingestion of MOAI within 2 weeks before starting study
  • Hypersensitivity/allergy to CBZ, any of the ingredients in CBZ, or any structurally related drugs (e.g. the tricyclic antidepressants)
  • History of liver failure or hepatitis
  • History of renal failure
  • History atrio-ventricular (AV) conduction abnormalities unless paced
  • History of bone marrow depression
  • History of porphyria
  • Asian heritage
  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: NCT00621751

Locations
United States, North Carolina
Carolinas Rehabilitation
Charlotte, North Carolina, United States, 28203
Sponsors and Collaborators
Carolinas Healthcare System
U.S. Department of Education
Investigators
Principal Investigator: Flora M Hammond, MD Carolinas Healthcare System
  More Information

Additional Information:
Publications:
Responsible Party: Flora Hammond, PI, Carolinas Healthcare System
ClinicalTrials.gov Identifier: NCT00621751     History of Changes
Other Study ID Numbers: 12-07-02A, NIDRR H133A
Study First Received: February 13, 2008
Last Updated: August 11, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by Carolinas Healthcare System:
Brain Injury
Irritability
Aggression

Additional relevant MeSH terms:
Brain Injuries
Aggression
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Craniocerebral Trauma
Trauma, Nervous System
Wounds and Injuries
Behavioral Symptoms
Carbamazepine
Anticonvulsants
Central Nervous System Agents
Therapeutic Uses
Pharmacologic Actions
Antimanic Agents
Tranquilizing Agents
Central Nervous System Depressants
Physiological Effects of Drugs
Psychotropic Drugs
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents

ClinicalTrials.gov processed this record on September 16, 2014