Approach-Avoidance Conflict-a Multi-level Predictor for Therapy Response

NCT02807480 | Completed Results

• 2 other identifiers: 2015-006-021K23MH108707-01A1
• Study Type: interventional
• Target: 121
• Locations: 1 country
• Sites: 1

Brief Summary

This project aims to identify brain and behavioral characteristics of individuals experiencing symptoms of generalized anxiety disorder that will predict the effectiveness of Exposure-based therapy versus Behavioral Activation Therapy. Brain imaging aspects of the study will use functional magnetic resonance imaging (fMRI) and electroencephalography (EEG). Behavioral assessments will include self-report questionnaires, computer-based and observational tasks, and interviews. Assessments will focus on how individuals process positive information (such as reward) and negative information (such as distressing images), as well as how people make decisions. These assessments will be conducted across 2-3 in-person sessions prior to beginning the treatment, and will be repeated across 2-3 in-person sessions after completing treatment. A blood draw will also be conducted pre- and post- treatment. Both the Exposure-based and Behavior Activation therapy will consist of 10, 90-minute weekly therapy sessions conducted in small groups.

Conditions

Generalized Anxiety Disorder

Outcome Measures

Primary Outcomes (2)

• For Aim1: Baseline Generalized Anxiety Disorder Symptoms as Measured by the Generalized Anxiety Disorder - 7 Item Scale (GAD-7).

  Test the relationship between imaging and behavioral factors and the level of symptoms at baseline assessment. Scores on the Generalized Anxiety Disorder - 7 item scale (GAD-7) range from 0 to 21, higher scores reflect greater symptom severity.

  Baseline assessment (one time point)

• For Aims 2 and 3: Change in Generalized Anxiety Disorder Symptoms as Measured by the Generalized Anxiety Disorder - 7 Item Scale (GAD-7).

  Test the predictive effects of imaging and behavioral factors on change in symptoms at baseline compared to within 6 weeks after completing treatment. Scores on the Generalized Anxiety Disorder - 7 item scale (GAD-7) range from 0 to 21, higher scores reflect greater symptom severity.

  Trajectory of change from pre- to post- treatment; last time point assessed within 6 weeks following last treatment session, on average at 16 weeks after baseline assessment.

Secondary Outcomes (5)

• Change in Anxiety Symptoms as Measured by the Patient Reported Outcomes Measurement Information System (PROMIS) Anxiety Scale.

  Trajectory of change from pre- to post- treatment; last time point assessed within 6 weeks following last treatment session, on average at 16 weeks after baseline assessment

• Change in Depressive Symptoms as Measured by the Patient Reported Outcomes Measurement Information System (PROMIS) Depression Scale.

  Trajectory of change from pre- to post- treatment; last time point assessed within 6 weeks following last treatment session, on average at 16 weeks after baseline assessment

• Change in Level of Disability as Measured by the Sheehan Disability Scale

  Trajectory of change from pre- to post- treatment; last time point assessed within 6 weeks following last treatment session, on average at 16 weeks after baseline assessment

• Worry Symptoms as Measured by the Penn State Worry Questionnaire

  Post- treatment; last time point assessed within 6 weeks following last treatment session, on average at 16 weeks after baseline assessment

• Depressive Symptoms as Measured by the Beck Depression Inventory - II.

  Post- treatment; last time point assessed within 6 weeks following last treatment session, on average at 16 weeks after baseline assessment

Study Arms (2)

Exposure-based therapy

EXPERIMENTAL

Participants will complete 10, 90-minute sessions of Exposure-based therapy, conducted using a group format. Each group will include 8-12 participants. Exposure-based therapy seeks to increase abilities to manage anxiety through repeated practice in facing the situations or thoughts that are the focus of worry or fear. All participants will complete computer-based behavioral assessments, surveys and interviews, functional magnetic resonance imaging (fMRI), and electroencephalography (EEG).

Behavioral: Exposure-based therapy; Behavioral: Computer-based behavioral assessment; Behavioral: Surveys and Interviews; Device: Magnetic resonance imaging (MRI); Device: Electroencephalography (EEG)

Behavioral Activation therapy

EXPERIMENTAL

Participants will complete 10, 90-minute sessions of Behavioral Activation therapy, conducted using a group format. Each group will include 8-12 participants. Behavioral Activation therapy seeks to target behaviors that might maintain or worsen negative mood. All participants will complete computer-based behavioral assessments, surveys and interviews, functional magnetic resonance imaging (fMRI), and electroencephalography (EEG).

Behavioral: Behavioral Activation therapy; Behavioral: Computer-based behavioral assessment; Behavioral: Surveys and Interviews; Device: Magnetic resonance imaging (MRI); Device: Electroencephalography (EEG)

Interventions

Exposure-based therapy BEHAVIORAL

Exposure-based therapy

Exposure-based therapy

Behavioral Activation therapy BEHAVIORAL

Behavioral Activation therapy

Behavioral Activation therapy

Computer-based behavioral assessment BEHAVIORAL

Computer-based tasks during which participants respond to images on the screen, including abstract images, emotional faces, and pleasant and unpleasant images.

Behavioral Activation therapy; Exposure-based therapy

Surveys and Interviews BEHAVIORAL

Surveys and interviews in which participants will be asked to answer questions related to their mental and physical health history and current symptoms.

Behavioral Activation therapy; Exposure-based therapy

Magnetic resonance imaging (MRI) DEVICE

Magnetic resonance imaging (MRI) will be used to obtain information concerning the structure of the brain, as well as to assess changes associated with blood flow in the brain while participants are completing behavioral tasks (see description of computer-based behavioral assessment intervention).

Behavioral Activation therapy; Exposure-based therapy

Electroencephalography (EEG) DEVICE

Electroencephalography (EEG) will be used to assess changes in the electrical activity of the brain while participants are completing behavioral tasks (see description of computer-based behavioral assessment intervention).

Behavioral Activation therapy; Exposure-based therapy

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Age: 18-55
• All genders
• All races
• Eligibility as clinically significant anxiety will be determined by:
• Scoring greater than 7 on the Overall Anxiety Severity and Impairment Scale (OASIS) or greater than 10 on the generalized anxiety disorder 7-item scale (GAD-7) and/or diagnosis of Generalized Anxiety Disorder.
• Self-report that they are interested in obtaining treatment for anxiety.
• Anxiety symptoms are the primary disorder of concern.
• Able to provide written, informed consent
• Have sufficient proficiency in English language to understand and complete interviews, questionnaires, and all other study procedures

You may not qualify if:

• Has a history of unstable liver or renal insufficiency; glaucoma; significant and unstable cardiac, vascular, pulmonary, gastrointestinal, endocrine, neurologic, hematologic, rheumatologic, or metabolic disturbance; or any other condition that would make participation not be in the best interest (e.g., compromise the well-being) of the subject or that could prevent, limit, or confound the protocol-specified assessments.
• A history of drug or alcohol abuse in the past 6 months,
• Has any of the following diagnostic and statistical manual (DSM-5) disorders:
• Schizophrenia Spectrum and Other Psychotic Disorders
• Bipolar and Related Disorders
• Obsessive-Compulsive and Related Disorders
• Anorexia or Bulimia Nervosa
• Substance use disorder within 6 months
• Moderate to severe traumatic brain injury (\>30 min. loss of consciousness or \>24 hours posttraumatic amnesia) or other neurocognitive disorder with evidence of neurological deficits, neurological disorders, or severe or unstable medical conditions that might be compromised by participation in the study.
• Active suicidal ideation with intent or plan
• Current use of a medication that could affect brain functioning (e.g., anxiolytics, antipsychotics, mood stabilizers). However, participants reporting current use of prescribed antidepressants (selective serotonin reuptake inhibitors \[SSRIs\]) will be included as long as the dose has been stable for 6 weeks prior to enrolling in the study.
• Prescription of a medication outside of the accepted range, as determined by the best clinical practices and current research
• Taking drugs that affect the fMRI hemodynamic response.
• MRI contraindications including: cardiac pacemaker, metal fragments in eyes/skin/body (shrapnel), aortic/aneurysm clips, prosthesis, by-pass surgery/coronary artery clips, hearing aid, heart valve replacement, shunt (ventricular or spinal), electrodes, metal plates/pins/screws/wires, or neuro/bio-stimulators (TENS unit), persons who have ever been a professional metal worker/welder, history of eye surgery/eyes washed out because of metal, vision problems uncorrectable with lenses, inability to lie still on one's back for 60-120 minutes; prior neurosurgery; tattoos or cosmetic makeup with metal dyes, unwillingness to remove body piercings, and pregnancy
• Unwillingness or inability to complete any of the major aspects of the study protocol, including magnetic resonance imaging (i.e., due to claustrophobia), blood draws, or behavioral assessment. However, failing to complete some individual aspects of these assessment sessions will be acceptable (i.e., being unwilling to answer individual items on some questionnaires or being unwilling to complete a behavioral task)

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, 74008, United States

Location

Related Publications (9)

• Cuijpers P, Sijbrandij M, Koole S, Huibers M, Berking M, Andersson G. Psychological treatment of generalized anxiety disorder: a meta-analysis. Clin Psychol Rev. 2014 Mar;34(2):130-40. doi: 10.1016/j.cpr.2014.01.002. Epub 2014 Jan 10.

  PMID: 24487344 BACKGROUND

• Arch JJ, Ayers CR. Which treatment worked better for whom? Moderators of group cognitive behavioral therapy versus adapted mindfulness based stress reduction for anxiety disorders. Behav Res Ther. 2013 Aug;51(8):434-42. doi: 10.1016/j.brat.2013.04.004. Epub 2013 May 2.

  PMID: 23747582 BACKGROUND

• Aupperle RL, Paulus MP. Neural systems underlying approach and avoidance in anxiety disorders. Dialogues Clin Neurosci. 2010;12(4):517-31. doi: 10.31887/DCNS.2010.12.4/raupperle.

  PMID: 21319496 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

• Aupperle RL, Sullivan S, Melrose AJ, Paulus MP, Stein MB. A reverse translational approach to quantify approach-avoidance conflict in humans. Behav Brain Res. 2011 Dec 1;225(2):455-63. doi: 10.1016/j.bbr.2011.08.003. Epub 2011 Aug 6.

  PMID: 21843556 BACKGROUND

• 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

• Berg H, McDermott TJ, Kuplicki R, Yeh HW, Thompson WK, Smith R, Akeman E, Kirlic N, Clausen A, Cannon M, White E, Martell CR, Wolitzky-Taylor KB, Craske MG, Abelson JL, Paulus MP, Aupperle RL. Prediction of generalized anxiety disorder treatment outcomes with neurobehavioral responses to approach-avoidance conflict: a randomized clinical trial. Transl Psychiatry. 2025 Jul 5;15(1):231. doi: 10.1038/s41398-025-03460-x.

  PMID: 40617801 DERIVED

• Berg H, Eun YJ, Yu X, McDermott TJ, Akeman E, Kuplicki R, Yeh HW, Thompson W, Martell CR, Wolitzky-Taylor KB, Craske MG, Paulus MP, Aupperle RL. Neural activity to reward and loss predicting treatment outcomes for adults with generalized anxiety disorder: A randomized clinical trial. J Mood Anxiety Disord. 2025 Mar;9:100107. doi: 10.1016/j.xjmad.2025.100107. Epub 2025 Jan 8.

  PMID: 40384942 DERIVED

• Berg H, Akeman E, McDermott TJ, Cosgrove KT, Kirlic N, Clausen A, Cannon M, Yeh HW, White E, Thompson WK, Choquette EM, Sturycz-Taylor CA, Cochran G, Ramirez S, Martell CR, Wolitzky-Taylor KB, Craske MG, Abelson JL, Paulus MP, Aupperle RL. A randomized clinical trial of behavioral activation and exposure-based therapy for adults with generalized anxiety disorder. J Mood Anxiety Disord. 2023 Jun;1:100004. doi: 10.1016/j.xjmad.2023.100004. Epub 2023 Jun 9.

  PMID: 38384390 DERIVED

MeSH Terms

Conditions

Generalized Anxiety Disorder

Interventions

Surveys and Questionnaires; Interviews as Topic; Magnetic Resonance Imaging; Electroencephalography

Condition Hierarchy (Ancestors)

Anxiety Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Data Collection; Epidemiologic Methods; Investigative Techniques; Health Care Evaluation Mechanisms; Quality of Health Care; Health Care Quality, Access, and Evaluation; Public Health; Environment and Public Health; Tomography; Diagnostic Imaging; Diagnostic Techniques and Procedures; Diagnosis; Diagnostic Techniques, Neurological; Electrodiagnosis

Results Point of Contact

• Title: Robin Aupperle
• Organization: Laureate Institute for Brain Research

raupperle@laureateinstitute.org

918-502-5744

Study Officials

• Robin L Aupperle, Ph.D.

  Laureate Institute for Brain Research

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 16, 2016
• First Posted: June 21, 2016
• Study Start: June 1, 2016
• Primary Completion: July 27, 2021
• Study Completion: March 4, 2022
• Last Updated: March 26, 2024
• Results First Posted: March 26, 2024

Record last verified: 2024-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, ANALYTIC CODE
• Time Frame: Data may be available for sharing after a request is received. The duration of time in which that data is shared will be determined on a case by case basis.

Locations

US (1)