Approach-Avoidance, Computational Framework for Predicting Behavioral Therapy Outcome (AAC-BeT)

NCT04426461 | Recruiting

• 2 other identifiers: 2020-003R01MH123691
• Study Type: interventional
• Target: 220
• Locations: 1 country
• Sites: 1

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.

Conditions

Anxiety; Depression

Outcome Measures

Primary Outcomes (2)

• Composite score from Hamilton Anxiety Rating Scale (HAM-A) and Hamilton Rating Scale for Depression (HAM-D)

  Composite score (averaging of the standardized Z scores) from the Hamilton Anxiety Rating Scale (HAM-A) and Hamilton Rating Scale for Depression (HAM-D). These Z scores will range from -3.0 to +3.0, with greater scores indicating more severe anxiety and depression symptoms or worse outcome.

  Up to 18 weeks after the baseline assessments

• Quinolinic Acid

  Peripheral serum concentration of Quinolinic Acid

  Up to 18 weeks after the baseline assessments

Secondary Outcomes (6)

• Sheehan Disability Scale

  Up to 18 weeks after the baseline assessments

• National Institute of Health (NIH) Patient Reported Outcome Measurement and Information System (PROMIS) Anxiety Scale

  Up to 18 weeks after the baseline assessments

• National Institute of Health (NIH) Patient Reported Outcome Measurement and Information System (PROMIS) Depression Scale

  Up to 18 weeks after the baseline assessments

• Kynurenic acid

  Up to 14 weeks after the baseline assessments

• Ratio of kynurenic acid to quinolinic acid

  Up to 14 weeks after the baseline assessments

Other Outcomes (9)

• Amygdala reactivity to negative outcomes

  Up to 14 weeks after the baseline assessments.

• Dorsolateral prefrontal cortex reactivity to conflict decisions

  Up to 14 weeks after the baseline assessments.

• Dorsal striatal reactivity to negative outcomes

  Up to 14 weeks after the baseline assessments.

Study Arms (3)

Behavioral activation

EXPERIMENTAL

Behavioral: Behavioral Activation

Exposure-based therapy

EXPERIMENTAL

Behavioral: Exposure-based therapy

Supportive therapy

ACTIVE COMPARATOR

Behavioral: Supportive therapy

Interventions

Behavioral Activation BEHAVIORAL

Behavioral activation will be delivered as a 10-week, manualized, behavioral intervention focused on enhancing engagement in meaningful and reinforcing activities.

Behavioral activation

Exposure-based therapy BEHAVIORAL

Exposure-based therapy will be delivered as a 10-week, manualized, behavioral intervention focused on decreasing avoidance to allow for inhibitory learning and challenging negative expectations.

Exposure-based therapy

Supportive therapy BEHAVIORAL

Supportive therapy will be delivered as a 10-week, manualized intervention focused on encouraging patients to talk openly about their thoughts, emotions, and any past or current concerns.

Supportive therapy

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Laureate Institute for Brain Research, Inc.: lead
• National Institute of Mental Health (NIMH): collaborator

Study Sites (1)

Laureate Institute for Brain Research

Tulsa, Oklahoma, 74136, United States

RECRUITING

Related Publications (2)

• 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.

  PMID: 31907032 BACKGROUND

• 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.

  PMID: 25224633 BACKGROUND

MeSH Terms

Conditions

Anxiety Disorders; Depression

Interventions

Palliative Care

Condition Hierarchy (Ancestors)

Mental Disorders; Behavioral Symptoms; Behavior

Intervention Hierarchy (Ancestors)

Patient Care; Therapeutics; Health Services; Health Care Facilities Workforce and Services

Study Officials

• Robin L Aupperle, PhD

  Laureate Institute for Brain Research

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Mallory Cannon, M.S.

CONTACT

918-581-4885; neurocatt@laureateinstitute.org

Robin L Aupperle, PhD

CONTACT

918-502-5744; raupperle@laureateinstitute.org

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: Interview-based assessments will be conducted by blinded clinical assessors and participants will be blinded until after completion of all baseline assessments.
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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).

Study Record Dates

• First Submitted: June 4, 2020
• First Posted: June 11, 2020
• Study Start: September 11, 2020
• Primary Completion: June 30, 2025
• Study Completion: June 30, 2025
• Last Updated: June 13, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ANALYTIC CODE
• Time Frame: Immediately after publication of results from the primary aims of this project.
• Access Criteria: User registration will be required to access or download files. As part of the registration process, users must agree to the conditions of use governing access to the public release data, including restrictions against attempting to identify study participants, destruction of the data after analyses are completed, reporting responsibilities, restrictions on redistribution of the data to third parties, and proper acknowledgement of the data resource.

Locations

US (1)