Traumatic Brain InjuryNCT00621751
Carbamazepine for the Treatment of Chronic Post-Traumatic Brain Injury Irritability and Aggression
A study testing Carbamazepine in people with Traumatic Brain Injury, run by Wake Forest University Health Sciences at 1 site in United States.
Trial summary
The purpose of this study is to determine if carbamazepine reduces irritability and aggression among individuals with traumatic brain injury Read more about this study
- Who is it for?
- Ages 16 to 75 years
- Conditions the study is for
- Traumatic Brain Injury
- What is being tested?
- Carbamazepine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 70 participants
- Where
- 1 siteUnited States
- Study dates
- Feb 2008to Oct 2013
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 16 to 75 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 23Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
Carolinas Rehabilitation
Charlotte, North Carolina, 28203
About this study
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
The purpose of this study is to determine if carbamazepine reduces irritability and aggression among individuals with traumatic brain injury
Read the detailed description
To achieve the enrollment of 66 needed, over enrollment of 70 subjects with 70 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 Beck Depression Inventory-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), and Global Impression of Change. The Beck Depression Inventory will be administered to the participant only at baseline for purposes of stratification of the randomization on depression. The Clinician Investigator will complete the Clinician Global Impressions scale 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.
- Conditions
- Traumatic Brain Injury
- Being tested
- Carbamazepine, Placebo
- Keywords
- Brain Injury, Irritability, Aggression
- Medical subject headings
- Brain Injuries, Traumatic, Brain Injuries, Aggression
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CarbamazepineDrug
Also called Tegretol
800 mg daily
PlaceboDrug
Placebo
| Study group | Role | What they receive |
|---|---|---|
| Carbamazepine | Experimental | Carbamazepine 800 mg daily Receives: Drug: Carbamazepine |
| Placebo | Placebo comparator | Placebo Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 42 days
Secondary outcomes (6)
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.
Measured: 42-day
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.
Measured: 42 days
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.
Measured: Day 42
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.
Measured: Day-42
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.
Measured: 42 days
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.
Measured: Day-42
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Feb 2008 (estimated)
- Study startFeb 2008
- Primary completionSep 2013
- Study completionOct 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Traumatic Brain InjuryStudies of the same condition, open and under way.
- More trials run by Wake Forest University Health SciencesThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 70 participants (actual)
Sponsor and investigators
- Lead sponsor
- Wake Forest University Health Sciences
- Sponsor type
- University, hospital or other
- Collaborators
- U.S. Department of Education
- Responsible party
- Sponsor
- Investigators
- Flora M Hammond, MD, Principal investigator, Wake Forest University Health Sciences
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00621751
- Sponsor's protocol ID
- 12-07-02A
- Other IDs
- H133A20016
- Status last verified
- Aug 2021
- First submitted
- 13 Feb 2008
- Last updated
- 22 Apr 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
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.
PubMed 10576463Chatham-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.
PubMed 8845710Lewin 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.
PubMed 1521112Wroblewski 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.
PubMed 9012550
Study at a glance
From the registry record, last updated by the sponsor on 22 Apr 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT00621751
- Acronym / sponsor ID
- 12-07-02A
- Conditions
- Traumatic Brain Injury
- Keywords
- Brain Injury, Irritability, Aggression
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 70 participants (actual)
- Lead sponsor
- Wake Forest University Health SciencesUniversity, hospital or other
- Collaborators
- U.S. Department of Education
- Study start
- Feb 2008
- Primary completion
- Sep 2013 (actual)
- Study completion
- Oct 2013 (actual)
- First posted
- 22 Feb 2008 (estimated)
- Results
- Posted 19 Aug 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to determine if carbamazepine reduces irritability and aggression among individuals with traumatic brain injury
Detailed description
To achieve the enrollment of 66 needed, over enrollment of 70 subjects with 70 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 Beck Depression Inventory-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), and Global Impression of Change. The Beck Depression Inventory will be administered to the participant only at baseline for purposes of stratification of the randomization on depression. The Clinician Investigator will complete the Clinician Global Impressions scale 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Carbamazepine | Experimental | Drug: CarbamazepineCarbamazepine 800 mg daily |
| Placebo | Placebo comparator | Drug: PlaceboPlacebo |
Who may qualify
- Ages
- 16 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (7 listed)
- 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
Key exclusion criteria (23 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CarbamazepineAlso: Tegretol800 mg daily | Drug | Carbamazepine |
| PlaceboPlacebo | Drug | Placebo |
Primary outcome
Neuropsychiatric Inventory Irritability-Aggression Domains Composite Measure -- Observer
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, 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.
6 secondary outcomes
Proportion of Participants With Minimal Clinically Important Difference -- Observer Rating
Time frame: 42-day
Global Impression of Change -- Observer
Time frame: 42 days
Neuropsychiatric Inventory Irritability-Aggression Domains Composite Measure Completed by Participant [Time Frame: 42 Days]
Time frame: Day 42
Proportion of Participants With Minimal Clinically Important Difference (MCID) -- Participant
Time frame: Day-42
Clinicians Global Impression of Change
Time frame: 42 days
Global Impression of Change -- Participant
Time frame: Day-42
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Apr 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 10576463Azouvi 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.
- Background: PubMed 8845710Chatham-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.
- Background: PubMed 1521112Lewin 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.
- Background: PubMed 9012550Wroblewski 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.
- Carolinas RehabilitationLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Flora M Hammond, MD principal investigator
Wake Forest University Health Sciences
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Carbamazepine in people with Traumatic Brain Injury, run by Wake Forest University Health Sciences at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 22 Apr 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 19 Aug 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Neuropsychiatric Inventory Irritability-Aggression Domains Composite Measure -- Observer (time frame: 42 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00621751, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Apr 2022.