Traumatic Brain Injury Clinical Trial
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
Verified date | August 2021 |
Source | Wake Forest University Health Sciences |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Interventional |
The purpose of this study is to determine if carbamazepine reduces irritability and aggression among individuals with traumatic brain injury
Status | Completed |
Enrollment | 70 |
Est. completion date | October 2013 |
Est. primary completion date | September 2013 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 16 Years to 75 Years |
Eligibility | 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 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 - Concurrent use of Monoamine Oxidase Inhibitors or ingestion of within 2 weeks before starting study - Hypersensitivity/allergy to carbamazepine, any of the ingredients in carbamazepine, or any structurally related drugs (e.g. the tricyclic antidepressants) - History of liver failure or hepatitis - History of renal failure - History atrio-ventricular conduction abnormalities unless paced - History of bone marrow depression - History of porphyria - Asian heritage |
Country | Name | City | State |
---|---|---|---|
United States | Carolinas Rehabilitation | Charlotte | North Carolina |
Lead Sponsor | Collaborator |
---|---|
Wake Forest University Health Sciences | U.S. Department of Education |
United States,
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. — View Citation
Chatham-Showalter PE. Carbamazepine for combativeness in acute traumatic brain injury. J Neuropsychiatry Clin Neurosci. 1996 Winter;8(1):96-9. — View Citation
Lewin J, Sumners D. Successful treatment of episodic dyscontrol with carbamazepine. Br J Psychiatry. 1992 Aug;161:261-2. — View Citation
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. — View Citation
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | 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 | Proportion of Participants With Minimal Clinically Important Difference -- Observer Rating | Proportion of participants with Minimal Clinically Important Difference (MCID) on Neuropsychiatric Inventory Irritability-Aggression Composite Measure completed by Observer. Specifically, the proportion of participants that experienced a decrease of > 1 (MCID) in the NPI-I/A Rasch construct score (i.e., participants that are considered to have meaningful reduction in irritability/aggression) from baseline to day-42 between the groups using a chi-square test. MCID was defined as 0.5 times the standard deviation of baseline scores. | 42-day | |
Secondary | Global Impression of Change -- Observer | Global Impression of Change (GIC) is a 5-item Likert Scale rated participants and observer impression of change in the person with TBI. Responses range 1 = much improved to 5 = much worse. | 42 days | |
Secondary | Neuropsychiatric Inventory Irritability-Aggression Domains Composite Measure Completed by Participant [Time Frame: 42 Days] | 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, a composite measure of participant-rated NPI-I & -A domains transformed to a Rasch logit scale running from 0 (best) to 100 (worse) units (i.e., participant-rated NPI-I/A Rasch construct scores). Mean day-42 participant-rated NPI-I/A Rasch construct scores were compared between placebo vs. CBZ using ANCOVA with baseline score as covariate. | Day 42 | |
Secondary | Proportion of Participants With Minimal Clinically Important Difference (MCID) -- Participant | Proportion of participants with Minimal Clinically Important Difference (MCID) on Neuropsychiatric Inventory Irritability-Aggression Composite Measure completed by Participant. Specifically, the proportion of participants that experienced a decrease of > 1 (MCID) in the NPI-I/A Rasch construct score (i.e., participants that are considered to have meaningful reduction in irritability/aggression) from baseline to day-42 between the groups using a chi-square test. MCID was defined as 0.5 times the standard deviation of baseline scores. | Day-42 | |
Secondary | Clinicians Global Impression of Change | Study physician's impression of change since study onset. Clinicians Global Impressions of Change (CGI) is a sensitive, standardized tool to assess psychopharmacologic treatment response completed by the study physician. The Global Improvement (GI) CGI subscale documented the clinician's impression of change. The GI uses a 7-point scale to assess beneficial and negative effects. Low GI values (1 -3) indicate improvement; higher values (4-7) represent worsening. | 42 days | |
Secondary | Global Impression of Change -- Participant | Global Impression of Change (GIC) is a 5-item Likert Scale rated participants and observer impression of change in the person with TBI. Responses range 1 = much improved to 5 = much worse. | Day-42 |
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