Trial Outcomes & Findings for Hostile Interpretation Bias Training to Treat Irritability (NCT NCT03592368)

Last Updated: 2024-04-23

Results Overview

Interpretation bias is measured by the indifference point of happy-angry judgments of a continuum of 15 images of face emotion expression that are morphed between completely happy=1 to completely angry=15 facial expressions. Indifference point is represented on this scale of 1 to 15 faces. It represents the point on the face continuum where judgements change from predominantly happy to predominantly angry. Indifference points have a minimum value of 1 and a maximum value of 15, though are typically in the middle of the face-emotion continuum, e.g. 7. Lower indifference points represent a higher bias towards hostile (or angry) judgments. Change in interpretation bias is the difference between the post- and pre-training indifference points. This can range from -14 to 14, with positive numbers reflecting the degree to which the happy/angry decision bias is shifted towards more happy judgements. High positive numbers reflect a greater increase in happy judgments.

Recruitment status

COMPLETED

Study phase

Target enrollment

97 participants

Primary outcome timeframe

Up to one day before and after the single 1 day training session of Interpretation bias training session.

Results posted on

2024-04-23

Participant Flow

Participant milestones

Participant milestones
Measure	Active IBT, Out of MRI IBT: Interpretation bias training	Sham IBT, Out of MRI IBT: Interpretation bias training	Active IBT, In MRI IBT: Interpretation bias training	Sham IBT, In MRI IBT: Interpretation bias training
Overall Study STARTED	29	26	20	22
Overall Study COMPLETED	28	24	20	21
Overall Study NOT COMPLETED	1	2	0	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Active IBT, Out of MRI IBT: Interpretation bias training	Sham IBT, Out of MRI IBT: Interpretation bias training	Sham IBT, In MRI IBT: Interpretation bias training
Overall Study Per protocol, randomized but not exposed to intervention due to COVID policy	0	1	0
Overall Study Adverse Event	0	0	1
Overall Study Per protocol, received intervention but with inadequate engagement for arm inclusion	1	1	0

Baseline Characteristics

Hostile Interpretation Bias Training to Treat Irritability

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Active IBT, Out of MRI n=28 Participants IBT: Interpretation bias training	Sham IBT, Out of MRI n=24 Participants IBT: Interpretation bias training	Active IBT, In MRI n=20 Participants IBT: Interpretation bias training	Sham IBT, In MRI n=21 Participants IBT: Interpretation bias training	Total n=93 Participants Total of all reporting groups
Race (NIH/OMB) Black or African American	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	0 Participants n=4 Participants	2 Participants n=21 Participants
Race (NIH/OMB) White	23 Participants n=5 Participants	23 Participants n=7 Participants	15 Participants n=5 Participants	19 Participants n=4 Participants	80 Participants n=21 Participants
Age, Continuous	15.2 years STANDARD_DEVIATION 1.31 • n=5 Participants	14.8 years STANDARD_DEVIATION 1.45 • n=7 Participants	15.2 years STANDARD_DEVIATION 1.55 • n=5 Participants	15.2 years STANDARD_DEVIATION 1.27 • n=4 Participants	15.1 years STANDARD_DEVIATION 1.38 • n=21 Participants
Sex: Female, Male Female	19 Participants n=5 Participants	13 Participants n=7 Participants	11 Participants n=5 Participants	11 Participants n=4 Participants	54 Participants n=21 Participants
Sex: Female, Male Male	9 Participants n=5 Participants	11 Participants n=7 Participants	9 Participants n=5 Participants	10 Participants n=4 Participants	39 Participants n=21 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	3 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants	4 Participants n=4 Participants	9 Participants n=21 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	25 Participants n=5 Participants	23 Participants n=7 Participants	19 Participants n=5 Participants	17 Participants n=4 Participants	84 Participants n=21 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Asian	1 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	1 Participants n=21 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) More than one race	3 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants	2 Participants n=4 Participants	9 Participants n=21 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	0 Participants n=4 Participants	1 Participants n=21 Participants
Region of Enrollment United States	28 participants n=5 Participants	24 participants n=7 Participants	20 participants n=5 Participants	21 participants n=4 Participants	93 participants n=21 Participants
Indifference Point	5.60 units on a morph continuum scale STANDARD_DEVIATION 1.40 • n=5 Participants	5.49 units on a morph continuum scale STANDARD_DEVIATION 1.13 • n=7 Participants	6.37 units on a morph continuum scale STANDARD_DEVIATION 6.50 • n=5 Participants	5.29 units on a morph continuum scale STANDARD_DEVIATION 1.36 • n=4 Participants	5.66 units on a morph continuum scale STANDARD_DEVIATION 1.31 • n=21 Participants

PRIMARY outcome

Timeframe: Up to one day before and after the single 1 day training session of Interpretation bias training session.

Population: Arms are collapsed across completing IBT in or out of the scanner.

Outcome measures

Outcome measures
Measure	Active IBT n=48 Participants IBT: Interpretation bias training	Sham IBT n=45 Participants IBT: Interpretation bias training
Change in Interpretation Bias	1.53 units on a scale Standard Deviation 1.05	0.55 units on a scale Standard Deviation 1.14

PRIMARY outcome

Timeframe: During the course of the 1 day single session of interpretation bias training session.

Amygdala functional connectivity to ventromedial prefrontal cortex is measured by covariance in fluctuations in blood oxygen-level dependent signal between these regions during functional magnetic resonance imaging (fMRI) during the course of training. The outcome measure is a count of these randomized participants for whom the fMRI measure is valid for the planned connectivity analysis. These participants completed the task in scanner with acceptable behavioral data and fMRI data. Quality control for fMRI included visual inspection of brain images for quality, coverage, and proper alignment across functional, anatomic and template images. The fMRI images passed analysis benchmarks of \<20% censored volumes and \<0.25 mm Euclidean distance average censored motion across the task. Censor thresholds are 0.3 mm Euclidean distance and 5% voxels with outlying intensity values.

Outcome measures

Outcome measures
Measure	Active IBT n=20 Participants IBT: Interpretation bias training	Sham IBT n=22 Participants IBT: Interpretation bias training
Neural Response in Threat Learning System.	16 Participants	18 Participants

SECONDARY outcome

Timeframe: During the course of the 1 day single interpretation bias training session.

Population: Collapsed across the in and out of scanner groups.

Learning rate as measured by a reinforcement learning computational model during IBT, please see the reference Stoddard et al., 2023, for model details. As in general reinforcement learning models, it is the proportion of prediction error that is applied to future expectations. In this trial, when a participant received feedback about a judgement they made of a face, the participant implicitly compares that feedback to their expectations about that face. The difference between the feedback and their expectations is called prediction error. The learning rate the proportion of this prediction error that is applied to future expectations across the learning session. In that way it represents learning. Learning rate is a continuous, unitless value. It ranges from 0, representing no learning, to 1, representing perfect learning. It is generally small. The learning rate reported here is its form estimated across face emotions (see Stoddard et al., 2023).

Outcome measures

Outcome measures
Measure	Active IBT n=48 Participants IBT: Interpretation bias training	Sham IBT n=45 Participants IBT: Interpretation bias training
Learning Rate	0.019 proportion of prediction error Interval 0.0098 to 0.039	0.017 proportion of prediction error Interval 0.0082 to 0.032

SECONDARY outcome

Timeframe: Within one week prior to Interpretation bias training and one week +/- 3 days after Interpretation bias training.

Irritability is the tendency towards anger and temper outburst as measured by the Affective Reactivity Index, a seven item scale. Each item has 3 response options which are coded as follows: "not true"=0, "somewhat true"=1, and "certainly true"=2. The first six items are summed to generate a total score that reflects the degree over irritability over the past week. The Affective Reactivity Index ranges from 0 to 12. Higher values reflect more irritability. What is reported here is the average post- minus pre-treatment score, by parent report. In these differences, negative values are in the unit of this scale and the absolute value represents the degree of irritability reduction.

Outcome measures

Outcome measures
Measure	Active IBT n=48 Participants IBT: Interpretation bias training	Sham IBT n=45 Participants IBT: Interpretation bias training
Irritability	-2.04 score on a scale Standard Deviation 2.07	-1.44 score on a scale Standard Deviation 2.65

Adverse Events

Active IBT, Out of MRI

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Sham IBT, Out of MRI

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Active IBT, In MRI

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Sham IBT, In MRI

Serious events: 1 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Active IBT, Out of MRI n=29 participants at risk IBT: Interpretation bias training	Sham IBT, Out of MRI n=26 participants at risk IBT: Interpretation bias training	Active IBT, In MRI n=20 participants at risk IBT: Interpretation bias training	Sham IBT, In MRI n=22 participants at risk IBT: Interpretation bias training
Psychiatric disorders Suicidal Behavior	0.00% 0/29 • Adverse event data were collected between randomization and the intervention (up to one week) and through the follow up period following IBT (one week) after interpretation bias training. The definitions of adverse events do not differ from the clinicaltrials.gov definition. Adverse event information was collected on follow up query for any clinically significant change.	0.00% 0/26 • Adverse event data were collected between randomization and the intervention (up to one week) and through the follow up period following IBT (one week) after interpretation bias training. The definitions of adverse events do not differ from the clinicaltrials.gov definition. Adverse event information was collected on follow up query for any clinically significant change.	0.00% 0/20 • Adverse event data were collected between randomization and the intervention (up to one week) and through the follow up period following IBT (one week) after interpretation bias training. The definitions of adverse events do not differ from the clinicaltrials.gov definition. Adverse event information was collected on follow up query for any clinically significant change.	4.5% 1/22 • Number of events 1 • Adverse event data were collected between randomization and the intervention (up to one week) and through the follow up period following IBT (one week) after interpretation bias training. The definitions of adverse events do not differ from the clinicaltrials.gov definition. Adverse event information was collected on follow up query for any clinically significant change.

Other adverse events

Other adverse events
Measure	Active IBT, Out of MRI n=29 participants at risk IBT: Interpretation bias training	Sham IBT, Out of MRI n=26 participants at risk IBT: Interpretation bias training	Active IBT, In MRI n=20 participants at risk IBT: Interpretation bias training	Sham IBT, In MRI n=22 participants at risk IBT: Interpretation bias training
Psychiatric disorders Suicidal Ideation	0.00% 0/29 • Adverse event data were collected between randomization and the intervention (up to one week) and through the follow up period following IBT (one week) after interpretation bias training. The definitions of adverse events do not differ from the clinicaltrials.gov definition. Adverse event information was collected on follow up query for any clinically significant change.	0.00% 0/26 • Adverse event data were collected between randomization and the intervention (up to one week) and through the follow up period following IBT (one week) after interpretation bias training. The definitions of adverse events do not differ from the clinicaltrials.gov definition. Adverse event information was collected on follow up query for any clinically significant change.	5.0% 1/20 • Number of events 1 • Adverse event data were collected between randomization and the intervention (up to one week) and through the follow up period following IBT (one week) after interpretation bias training. The definitions of adverse events do not differ from the clinicaltrials.gov definition. Adverse event information was collected on follow up query for any clinically significant change.	0.00% 0/22 • Adverse event data were collected between randomization and the intervention (up to one week) and through the follow up period following IBT (one week) after interpretation bias training. The definitions of adverse events do not differ from the clinicaltrials.gov definition. Adverse event information was collected on follow up query for any clinically significant change.

Additional Information

Joel Stoddard

University of Colorado, Anschutz Medical Campus

Phone: (720) 777-5702

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place