Trial Outcomes & Findings for Carbamazepine for the Treatment of Chronic Post-Traumatic Brain Injury Irritability and Aggression (NCT NCT00621751)

Last Updated: 2022-04-22

Results Overview

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.

Recruitment status

COMPLETED

Study phase

Target enrollment

70 participants

Primary outcome timeframe

42 days

Results posted on

2022-04-22

Participant Flow

Participant milestones

Participant milestones
Measure	Carbamazepine Carbamazepine 800 mg daily Carbamazepine: 800 mg daily	Placebo Placebo Placebo: Placebo
Overall Study STARTED	35	35
Overall Study COMPLETED	35	34
Overall Study NOT COMPLETED	0	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Carbamazepine Carbamazepine 800 mg daily Carbamazepine: 800 mg daily	Placebo Placebo Placebo: Placebo
Overall Study Adverse Event	0	1

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Carbamazepine n=35 Participants Carbamazepine 800 mg daily Carbamazepine: 800 mg daily	Placebo n=35 Participants Placebo Placebo: Placebo	Total n=70 Participants Total of all reporting groups
Age, Continuous	40.2 years STANDARD_DEVIATION 12.9 • n=93 Participants	40.5 years STANDARD_DEVIATION 13.7 • n=4 Participants	40.4 years STANDARD_DEVIATION 13.2 • n=27 Participants
Sex: Female, Male Female	25 Participants n=93 Participants	28 Participants n=4 Participants	53 Participants n=27 Participants
Sex: Female, Male Male	10 Participants n=93 Participants	7 Participants n=4 Participants	17 Participants n=27 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=93 Participants	1 Participants n=4 Participants	1 Participants n=27 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	35 Participants n=93 Participants	33 Participants n=4 Participants	68 Participants n=27 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=93 Participants	1 Participants n=4 Participants	1 Participants n=27 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race (NIH/OMB) Asian	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race (NIH/OMB) Black or African American	7 Participants n=93 Participants	11 Participants n=4 Participants	18 Participants n=27 Participants
Race (NIH/OMB) White	28 Participants n=93 Participants	24 Participants n=4 Participants	52 Participants n=27 Participants
Race (NIH/OMB) More than one race	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants

PRIMARY outcome

Timeframe: 42 days

Outcome measures

Outcome measures
Measure	Carbamazepine n=35 Participants Carbamazepine 800 mg daily Carbamazepine: 800 mg daily	Placebo n=34 Participants Placebo Placebo: Placebo
Neuropsychiatric Inventory Irritability-Aggression Domains Composite Measure -- Observer	37.7 score on a scale Standard Error 1.4	36.7 score on a scale Standard Error 1.5

SECONDARY outcome

Timeframe: 42-day

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.

Outcome measures

Outcome measures
Measure	Carbamazepine n=35 Participants Carbamazepine 800 mg daily Carbamazepine: 800 mg daily	Placebo n=34 Participants Placebo Placebo: Placebo
Proportion of Participants With Minimal Clinically Important Difference -- Observer Rating	20 Participants	26 Participants

SECONDARY outcome

Timeframe: 42 days

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.

Outcome measures

Outcome measures
Measure	Carbamazepine n=35 Participants Carbamazepine 800 mg daily Carbamazepine: 800 mg daily	Placebo n=34 Participants Placebo Placebo: Placebo
Global Impression of Change -- Observer	3.3 units on a scale Standard Deviation 1.4	3.1 units on a scale Standard Deviation 0.9

SECONDARY outcome

Timeframe: Day 42

Population: There were fewer participants scores than observers scores.

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.

Outcome measures

Outcome measures
Measure	Carbamazepine n=32 Participants Carbamazepine 800 mg daily Carbamazepine: 800 mg daily	Placebo n=30 Participants Placebo Placebo: Placebo
Neuropsychiatric Inventory Irritability-Aggression Domains Composite Measure Completed by Participant [Time Frame: 42 Days]	37.5 score on a scale Standard Error 1.4	36.4 score on a scale Standard Error 1.4

SECONDARY outcome

Timeframe: Day-42

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.

Outcome measures

Outcome measures
Measure	Carbamazepine n=32 Participants Carbamazepine 800 mg daily Carbamazepine: 800 mg daily	Placebo n=30 Participants Placebo Placebo: Placebo
Proportion of Participants With Minimal Clinically Important Difference (MCID) -- Participant	21 Participants	16 Participants

SECONDARY outcome

Timeframe: 42 days

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.

Outcome measures

Outcome measures
Measure	Carbamazepine n=35 Participants Carbamazepine 800 mg daily Carbamazepine: 800 mg daily	Placebo n=34 Participants Placebo Placebo: Placebo
Clinicians Global Impression of Change	3.1 units on a scale Standard Deviation 1.3	2.9 units on a scale Standard Deviation 1.1

SECONDARY outcome

Timeframe: Day-42

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.

Outcome measures

Outcome measures
Measure	Carbamazepine n=32 Participants Carbamazepine 800 mg daily Carbamazepine: 800 mg daily	Placebo n=30 Participants Placebo Placebo: Placebo
Global Impression of Change -- Participant	3.1 score on a scale Standard Deviation 1.3	3.1 score on a scale Standard Deviation 0.9

Adverse Events

Carbamazepine

Serious events: 6 serious events

Other events: 29 other events

Deaths: 0 deaths

Placebo

Serious events: 1 serious events

Other events: 19 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Carbamazepine n=35 participants at risk Carbamazepine 800 mg daily Carbamazepine: 800 mg daily	Placebo n=35 participants at risk Placebo Placebo: Placebo
Blood and lymphatic system disorders Blood & lymphatic	2.9% 1/35 • Number of events 1 • 42 days plus additional 30 days.	0.00% 0/35 • 42 days plus additional 30 days.
Cardiac disorders Cardiac	2.9% 1/35 • Number of events 1 • 42 days plus additional 30 days.	0.00% 0/35 • 42 days plus additional 30 days.
General disorders General disorders & administration conditions	2.9% 1/35 • Number of events 1 • 42 days plus additional 30 days.	0.00% 0/35 • 42 days plus additional 30 days.
Infections and infestations Infections	2.9% 1/35 • Number of events 1 • 42 days plus additional 30 days.	0.00% 0/35 • 42 days plus additional 30 days.
Injury, poisoning and procedural complications Injury	2.9% 1/35 • Number of events 1 • 42 days plus additional 30 days.	0.00% 0/35 • 42 days plus additional 30 days.
Investigations Lab Investigations	2.9% 1/35 • Number of events 1 • 42 days plus additional 30 days.	0.00% 0/35 • 42 days plus additional 30 days.
Nervous system disorders Nervous system	0.00% 0/35 • 42 days plus additional 30 days.	2.9% 1/35 • Number of events 1 • 42 days plus additional 30 days.
Psychiatric disorders Psychiatric disorders	2.9% 1/35 • Number of events 1 • 42 days plus additional 30 days.	0.00% 0/35 • 42 days plus additional 30 days.
Skin and subcutaneous tissue disorders Skin	2.9% 1/35 • Number of events 1 • 42 days plus additional 30 days.	0.00% 0/35 • 42 days plus additional 30 days.

Other adverse events

Other adverse events
Measure	Carbamazepine n=35 participants at risk Carbamazepine 800 mg daily Carbamazepine: 800 mg daily	Placebo n=35 participants at risk Placebo Placebo: Placebo
Cardiac disorders Cardiac disprders	5.7% 2/35 • Number of events 2 • 42 days plus additional 30 days.	0.00% 0/35 • 42 days plus additional 30 days.
Gastrointestinal disorders Gastrointestinal disorders	14.3% 5/35 • Number of events 5 • 42 days plus additional 30 days.	5.7% 2/35 • Number of events 2 • 42 days plus additional 30 days.
General disorders General disorders & administration conditions	8.6% 3/35 • Number of events 3 • 42 days plus additional 30 days.	2.9% 1/35 • Number of events 1 • 42 days plus additional 30 days.
Injury, poisoning and procedural complications Injury	5.7% 2/35 • Number of events 2 • 42 days plus additional 30 days.	0.00% 0/35 • 42 days plus additional 30 days.
Investigations Lab results	8.6% 3/35 • Number of events 3 • 42 days plus additional 30 days.	0.00% 0/35 • 42 days plus additional 30 days.
Metabolism and nutrition disorders Metabolic	5.7% 2/35 • Number of events 2 • 42 days plus additional 30 days.	5.7% 2/35 • Number of events 2 • 42 days plus additional 30 days.
Musculoskeletal and connective tissue disorders Musculoskeletal	2.9% 1/35 • Number of events 1 • 42 days plus additional 30 days.	5.7% 2/35 • Number of events 2 • 42 days plus additional 30 days.
Nervous system disorders Nervous system	57.1% 20/35 • Number of events 20 • 42 days plus additional 30 days.	31.4% 11/35 • Number of events 11 • 42 days plus additional 30 days.
Psychiatric disorders Psychiatric	25.7% 9/35 • Number of events 9 • 42 days plus additional 30 days.	14.3% 5/35 • Number of events 5 • 42 days plus additional 30 days.
Skin and subcutaneous tissue disorders Skin	14.3% 5/35 • Number of events 5 • 42 days plus additional 30 days.	5.7% 2/35 • Number of events 2 • 42 days plus additional 30 days.
Vascular disorders Vascular	8.6% 3/35 • Number of events 3 • 42 days plus additional 30 days.	2.9% 1/35 • Number of events 1 • 42 days plus additional 30 days.

Additional Information

Flora Hammond, MD

Atrium Health; Currently at Indiana University School of Medicine

Phone: 317-292-6781

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place