Clinical trial NCT04426461: Approach-Avoidance, Computational Framework for Predicting Behavioral Therapy Outcome (AAC-BeT)
Official title: An Approach-Avoidance, Computational Framework for Predicting Behavioral Therapy Outcome in Anxiety and Depression (AAC-BeT)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Anxiety
Depression
Lead sponsor: Laureate Institute for Brain Research, Inc.
Sponsor class: OTHER
Collaborators: name: National Institute of Mental Health (NIMH)
First posted: 2020-06-11
Enrollment: 220
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Participants will be randomized to behavioral activation, exposure-based, or supportive therapy according to parallel assignment, stratified by sex (male, female) and symptom severity (mild, moderate, severe).
Primary purpose: BASIC_SCIENCE

Brief summary: Depression and anxiety disorders rank in the top ten causes of years lived with disability. Less than 50% of patients experiencing long-lasting improvements to current gold-standard treatments. Two gold-standard behavioral interventions include behavioral activation, focused on enhancing approach behavior towards meaningful activities, and exposure-based therapy, focused on decreasing avoidance and challenging negative expectations. While these interventions have divergent treatment targets, there is little knowledge to inform which strategies should be used in the frequent case of comorbid anxiety and depression. Approach-avoidance decision-making paradigms focus on assessing responses when faced with potential rewards and threats, tapping into processes important for both anxiety and depression as well as behavioral activation and exposure-based therapy.

For this study, investigators will recruit individuals reporting both anxiety and depression symptoms and randomize them to one of three different interventions: (1) behavioral activation, (2) exposure-based therapy, and a non-specific therapy approach (3) supportive therapy. Participants will complete clinical, self-report, behavioral, and functional magnetic resonance imaging (fMRI) assessments before and after therapy. Investigators will use a computational approach to model factors that may influence one's behavior during approach-avoidance decision-making, including drives to avoid threat versus approach reward and confidence versus uncertainty in one's decisions.

This project will accomplish the following aims (1) Determine how changes in brain and behavior responses during approach-avoidance conflict relate to changes in mental health symptoms with the different therapy approaches, (2) Determine the degree to which baseline brain and behavior responses during approach-avoidance conflict predict response to the different therapy approaches, above and beyond the influence of demographics and baseline symptom severity. In addition, by including peripheral blood draws and measures of grace matter volume, the project will also accomplish the following aims: (1) Determine whether kynrenine metabolites measures peripherally may be beneficial as a biomarker of treatment response and (2) determine whether there is an association between change in kynurenine metabolites and changes in gray matter volume with treatment.

Results will enhance understanding of how different psychotherapy approaches (behavioral activation, exposure-based therapy) may impact brain responses and decisions when faces with potential reward versus threat and approach versus avoidance drives. In addition, results will have important implications concerning the potential for a more personalized approach to psychotherapy, enhancing knowledge of which types of therapy strategies may be most beneficial for which individuals.


Eligibility criteria: Inclusion Criteria:

* score \>55 on both the PROMIS Anxiety and PROMIS Depression scales
* score \>5 on any one item of the SDS
* able to provide informed consent
* report of anxiety and depressive symptoms as areas of clinical concern
* sufficient English proficiency to complete procedures.

Exclusion Criteria:

* significant or unstable physical or mental health conditions (e.g., immediate suicidal intent) requiring medical attention
* history of bipolar, psychotic, cognitive, obsessive compulsive disorder, posttraumatic stress disorder (PTSD)
* history of moderate to severe substance use disorder over the past year
* diagnosis of neurologic disorders
* MRI contra-indications (e.g., metal in body)
* uncorrected vision/hearing problems
* current, regular benzodiazepine use

Primary outcomes:
measure: Composite score from Hamilton Anxiety Rating Scale (HAM-A) and Hamilton Rating Scale for Depression (HAM-D)
timeFrame: Up to 18 weeks after the baseline assessments
measure: Quinolinic Acid
timeFrame: Up to 18 weeks after the baseline assessments
Secondary outcomes:
measure: Sheehan Disability Scale
timeFrame: Up to 18 weeks after the baseline assessments
measure: National Institute of Health (NIH) Patient Reported Outcome Measurement and Information System (PROMIS) Anxiety Scale
timeFrame: Up to 18 weeks after the baseline assessments
measure: National Institute of Health (NIH) Patient Reported Outcome Measurement and Information System (PROMIS) Depression Scale
timeFrame: Up to 18 weeks after the baseline assessments
measure: Kynurenic acid
timeFrame: Up to 14 weeks after the baseline assessments
measure: Ratio of kynurenic acid to quinolinic acid
timeFrame: Up to 14 weeks after the baseline assessments
measure: Ratio of kynurenic acid to tryptophan
timeFrame: Up to 18 weeks after the baseline assessments
Other outcomes:
measure: Amygdala reactivity to negative outcomes
timeFrame: Up to 14 weeks after the baseline assessments.
measure: Dorsolateral prefrontal cortex reactivity to conflict decisions
timeFrame: Up to 14 weeks after the baseline assessments.
measure: Dorsal striatal reactivity to negative outcomes
timeFrame: Up to 14 weeks after the baseline assessments.
measure: Decision uncertainty during approach-avoidance conflict decision making
timeFrame: Up to 14 weeks after the baseline assessments.
measure: Emotional conflict during approach-avoidance conflict decision making
timeFrame: Up to 14 weeks after the baseline assessments.
measure: Approach behavior during approach-avoidance conflict decision making
timeFrame: Up to 14 weeks after the baseline assessments.
measure: Bilateral amygdala volume
timeFrame: Up to 14 weeks after the baseline assessments.
measure: Bilateral striatal volume
timeFrame: Up to 14 weeks after the baseline assessments.
measure: Bilateral hippocampal volume
timeFrame: Up to 14 weeks after the baseline assessments.
Locations:
city: Tulsa
country: United States
facility: Laureate Institute for Brain Research
state: Oklahoma
Study officials:
affiliation: Laureate Institute for Brain Research
name: Robin L Aupperle, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Santiago J, Akeman E, Kirlic N, Clausen AN, Cosgrove KT, McDermott TJ, Mathis B, Paulus M, Craske MG, Abelson J, Martell C, Wolitzky-Taylor K, Bodurka J, Thompson WK, Aupperle RL. Protocol for a randomized controlled trial examining multilevel prediction of response to behavioral activation and exposure-based therapy for generalized anxiety disorder. Trials. 2020 Jan 6;21(1):17. doi: 10.1186/s13063-019-3802-9.
citation: Aupperle RL, Melrose AJ, Francisco A, Paulus MP, Stein MB. Neural substrates of approach-avoidance conflict decision-making. Hum Brain Mapp. 2015 Feb;36(2):449-62. doi: 10.1002/hbm.22639. Epub 2014 Sep 15.