Trial Outcomes & Findings for Brain Emotion Circuitry-Targeted Self-Monitoring and Regulation Therapy (BE-SMART) (NCT NCT03183388)

NCT ID: NCT03183388

Last Updated: 2024-02-29

Results Overview

FMRI was performed during an emotional face processing task. Signal differences (BOLD changes) were compared between baseline and endpoint, separately for BE-SMART-DR or BE-SMART-ER, at a voxel-level threshold of p\<0.001 uncorrected using statistical parametric mapping (SPM) software. If voxels above this threshold survived in a hypothesized region of interest (amygdala and ventral prefrontal cortex, VPFC) then the signal differences in those voxels were extracted and mean values within the region for each subject were used in the analyses below. The only voxel-based finding meeting criteria was left amygdala activation decreases to fearful faces in participants receiving BE-SMART-DR. The results of the mixed model analysis of those values are below.

• Recruitment status: COMPLETED
• Study phase: NA
• Target enrollment: 76 participants
• Primary outcome timeframe: baseline and 12 weeks
• Results posted on: 2024-02-29

Participant Flow

76 participants were enrolled and 60 started

Participant milestones

Measure	BE-SMART DR Adolescents and young adults with BD who received baseline scan and Brain Emotion Circuitry Targeted Self-Monitoring Regulation Daily Rhythms (BE-SMART DR)	BE-SMART ER Adolescents and young adults with bipolar disorder (BD) who received baseline scan and Brain Emotion Circuitry Targeted Self- Monitoring Regulation Therapy Emotion Regulation (BE-SMART ER)
Overall Study STARTED	30	30
Overall Study Completed Mid-point	20	19
Overall Study Completed Participation in Intervention and Endpoint Assessment	19	16
Overall Study Completed All Procedures Including Endpoint Imaging	17	14
Overall Study COMPLETED	17	14
Overall Study NOT COMPLETED	13	16

Reasons for withdrawal

Measure	BE-SMART DR Adolescents and young adults with BD who received baseline scan and Brain Emotion Circuitry Targeted Self-Monitoring Regulation Daily Rhythms (BE-SMART DR)	BE-SMART ER Adolescents and young adults with bipolar disorder (BD) who received baseline scan and Brain Emotion Circuitry Targeted Self- Monitoring Regulation Therapy Emotion Regulation (BE-SMART ER)
Overall Study Lost to Follow-up	3	5
Overall Study Physician Decision	1	4
Overall Study Withdrawal by Subject	4	1
Overall Study Moved	1	0
Overall Study Met Exclusion Criteria	2	2
Overall Study COVID Pandemic Related	2	4

Baseline Characteristics

Brain Emotion Circuitry-Targeted Self-Monitoring and Regulation Therapy (BE-SMART)

Baseline characteristics by cohort

Measure	BE-SMART ER n=30 Participants Adolescents and young adults with BD who received baseline scan and Brain Emotion Circuitry Targeted Self- Monitoring Regulation Therapy Emotion Regulation (BE-SMART ER)	BE-SMART DR n=30 Participants Adolescents and young adults with BD who received baseline scan and Brain Emotion Circuitry Targeted Self-Monitoring Regulation Daily Rhythms (BE-SMART DR)	Total n=60 Participants Total of all reporting groups
Age, Categorical <=18 years	4 Participants n=5 Participants	7 Participants n=7 Participants	11 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	26 Participants n=5 Participants	23 Participants n=7 Participants	49 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Sex: Female, Male Female	19 Participants n=5 Participants	20 Participants n=7 Participants	39 Participants n=5 Participants
Sex: Female, Male Male	11 Participants n=5 Participants	10 Participants n=7 Participants	21 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	3 Participants n=5 Participants	6 Participants n=7 Participants	9 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	27 Participants n=5 Participants	24 Participants n=7 Participants	51 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	3 Participants n=5 Participants	3 Participants n=7 Participants	6 Participants n=5 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
Race (NIH/OMB) Black or African American	1 Participants n=5 Participants	4 Participants n=7 Participants	5 Participants n=5 Participants
Race (NIH/OMB) White	23 Participants n=5 Participants	21 Participants n=7 Participants	44 Participants n=5 Participants
Race (NIH/OMB) More than one race	3 Participants n=5 Participants	2 Participants n=7 Participants	5 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment United States	30 participants n=5 Participants	30 participants n=7 Participants	60 participants n=5 Participants

PRIMARY outcome

Timeframe: baseline and 12 weeks

Population: Adolescents and young adults with bipolar disorder (BD) who received intervention and had both baseline and endpoint fMRI data of sufficient quality were analyzed. Voxel-level threshold for BE-SMART-ER did not reach p\<0.001 uncorrected threshold and therefore there were no extracted values for further analyses.

FMRI was performed during an emotional face processing task. Signal differences (BOLD changes) were compared between baseline and endpoint, separately for BE-SMART-DR or BE-SMART-ER, at a voxel-level threshold of p<0.001 uncorrected using statistical parametric mapping (SPM) software. If voxels above this threshold survived in a hypothesized region of interest (amygdala and ventral prefrontal cortex, VPFC) then the signal differences in those voxels were extracted and mean values within the region for each subject were used in the analyses below. The only voxel-based finding meeting criteria was left amygdala activation decreases to fearful faces in participants receiving BE-SMART-DR. The results of the mixed model analysis of those values are below.

Outcome measures

Measure	BE-SMART DR n=11 Participants Adolescents and young adults with BD who received baseline and endpoint scans and BE-SMART-DR and had fMRI activation data at both timepoints of sufficient quality for analyses.	BE-SMART ER Adolescents and young adults with BD who received baseline and endpoint scans and BE-SMART-ER and had fMRI activation data at both timepoints of sufficient quality for analyses.
Functional Magnetic Resonance Imaging (fMRI) Blood Oxygen-level Dependent (BOLD) Signal Changes in Left Amygdala at Baseline and at the End of the Intervention Baseline	1.62 BOLD signal Standard Error 0.64	—
Functional Magnetic Resonance Imaging (fMRI) Blood Oxygen-level Dependent (BOLD) Signal Changes in Left Amygdala at Baseline and at the End of the Intervention 12 weeks	-1.42 BOLD signal Standard Error 0.64	—

PRIMARY outcome

Timeframe: Baseline and 6 weeks

Population: Adolescents and young adults with BD who received BE-SMART-DR and who had fMRI data at both at baseline and midpoint. Voxel-level threshold for BE-SMART-ER did not reach the p\<0.001 uncorrected threshold and therefore there were no extracted values for further analyses.

Signal differences (BOLD changes) between baseline and midpoint in regions of interest that survived the voxel-based threshold in participants who received either BE-SMART variation and had fMRI data of sufficient quality for fMRI activation analyses. The results of the mixed model analyses of those values are below.

Outcome measures

Measure	BE-SMART DR n=11 Participants Adolescents and young adults with BD who received baseline and endpoint scans and BE-SMART-DR and had fMRI activation data at both timepoints of sufficient quality for analyses.	BE-SMART ER Adolescents and young adults with BD who received baseline and endpoint scans and BE-SMART-ER and had fMRI activation data at both timepoints of sufficient quality for analyses.
FMRI BOLD Signal Changes in Left Amygdala at Baseline and Midpoint Baseline	1.42 BOLD signal Standard Error 0.75	—
FMRI BOLD Signal Changes in Left Amygdala at Baseline and Midpoint 6 weeks	0.053 BOLD signal Standard Error 1.93	—

PRIMARY outcome

Timeframe: Baseline and 12 weeks

Population: Only adolescents and young adults with BD who had baseline and endpoint fMRI functional connectivity data of sufficient quality were analyzed. Voxel-level threshold for BE-SMART-ER did not reach the p\<0.001 uncorrected threshold and therefore there were no extracted values for further analyses.

Pearson's correlations between the mean timecourse of the seed and the timecourse of each voxel between baseline and endpoint were compared at a voxel-level threshold of p<0.001 uncorrected using statistical parametric mapping (SPM) software. If there were voxels above this threshold in the hypothesized region of interest (ventral prefrontal cortex), then the correlation values from those voxels in that region were extracted and Fisher transformed and averaged, where higher scores indicted greater connectivity. Functional connectivity differences between baseline and endpoint in regions of interest that survived the voxel-based threshold in participants who received either BE-SMART variation and had fMRI data of sufficient quality for fMRI functional connectivity analyses. The results of the mixed model analysis of those values are below.

Outcome measures

Measure	BE-SMART DR n=11 Participants Adolescents and young adults with BD who received baseline and endpoint scans and BE-SMART-DR and had fMRI activation data at both timepoints of sufficient quality for analyses.	BE-SMART ER Adolescents and young adults with BD who received baseline and endpoint scans and BE-SMART-ER and had fMRI activation data at both timepoints of sufficient quality for analyses.
fMRI Functional Connectivity Changes in VPFC From an Amygdala Seed Region at Baseline and Endpoint Baseline	-0.057 Z-transformed correlation coefficient Standard Error 0.017	—
fMRI Functional Connectivity Changes in VPFC From an Amygdala Seed Region at Baseline and Endpoint 12 weeks	0.052 Z-transformed correlation coefficient Standard Error 0.017	—

PRIMARY outcome

Timeframe: Baseline and 6 weeks

Population: Adolescents and young adults with BD who received BE-SMART-DR with fMRI functional connectivity data at both baseline and midpoint. Voxel-level threshold for BE-SMART-ER did not reach the p\<0.001 uncorrected threshold and therefore there were no extracted values for further analyses.

Pearson's correlations between the mean timecourse of the seed and the timecourse of each voxel between baseline and midpoint were compared at a voxel-level threshold of p<0.001 uncorrected using statistical parametric mapping (SPM) software. If there were voxels above this threshold in the hypothesized region of interest (ventral prefrontal cortex), then the correlation values from those voxels in that region were extracted and Fisher transformed and averaged where higher scores indicte greater connectivity. Functional connectivity differences between baseline and midpoint in regions of interest that survived the voxel-based threshold in participants who received either BE-SMART variation and had fMRI data of sufficient quality for fMRI functional connectivity analyses. The results of the mixed model analysis of those values are below.

Outcome measures

Measure	BE-SMART DR n=9 Participants Adolescents and young adults with BD who received baseline and endpoint scans and BE-SMART-DR and had fMRI activation data at both timepoints of sufficient quality for analyses.	BE-SMART ER Adolescents and young adults with BD who received baseline and endpoint scans and BE-SMART-ER and had fMRI activation data at both timepoints of sufficient quality for analyses.
fMRI Functional Connectivity Changes in VPFC From an Amygdala Seed Region at Baseline and Midpoint Baseline	-0.038 Z-transformed correlation coefficient Standard Error 0.026	—
fMRI Functional Connectivity Changes in VPFC From an Amygdala Seed Region at Baseline and Midpoint 6 weeks	-0.0068 Z-transformed correlation coefficient Standard Error 0.046	—

Adverse Events

BE-SMART

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Dr. Hilary Blumberg

Yale School of Medicine

Phone: 203-785-6180

Email: hilary.blumberg@yale.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place