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

February 13, 2008
August 11, 2014
February 2008
September 2013   (final data collection date for primary outcome measure)
Neuropsychiatric Inventory Irritability Domain (frequency and severity) completed by observer [ Time Frame: 42 days ] [ Designated as safety issue: No ]
  • Neuropsychiatric Inventory Irritability Domain (frequency and severity) completed by caregiver [ Time Frame: 42 days ] [ Designated as safety issue: No ]
  • Clinicians Global Impression of Change [ Time Frame: 42 days ] [ Designated as safety issue: No ]
Complete list of historical versions of study NCT00621751 on ClinicalTrials.gov Archive Site
  • 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
  • Neuropsychiatric Inventory Aggression Domain (frequency, severity, and caregiver distress) completed by the caregiver [ Time Frame: 42 days ] [ Designated as safety issue: No ]
  • Neuropsychiatric Inventory Irritability Domain (caregiver distress) completed by the caregiver [ 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 caregiver [ 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 ]
Not Provided
Not Provided
 
Carbamazepine for the Treatment of Chronic Post-Traumatic Brain Injury Irritability and Aggression
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

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

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.

Interventional
Not Provided
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Traumatic Brain Injury
  • Drug: Carbamazepine
    800 mg daily
    Other Name: Tegretol
  • Drug: Placebo
    Placebo
  • Experimental: A
    Carbamazepine 800 mg daily
    Intervention: Drug: Carbamazepine
  • Placebo Comparator: B
    Placebo
    Intervention: Drug: Placebo

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
74
October 2013
September 2013   (final data collection date for primary outcome measure)

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
Both
16 Years to 75 Years
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00621751
12-07-02A, NIDRR H133A
Yes
Flora Hammond, Carolinas Healthcare System
Carolinas Healthcare System
U.S. Department of Education
Principal Investigator: Flora M Hammond, MD Carolinas Healthcare System
Carolinas Healthcare System
August 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP