Generalized Anxiety DisorderNCT02807480
Approach-Avoidance Conflict-a Multi-level Predictor for Therapy Response
A study testing Exposure-based therapy, Behavioral Activation therapy and Computer-based behavioral assessment in people with Generalized Anxiety Disorder, run by Laureate Institute for Brain Research, Inc. at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 55 years
- Conditions the study is for
- Generalized Anxiety Disorder
- What is being tested?
- Exposure-based therapy, Behavioral Activation therapy and Computer-based behavioral assessment
- Type of treatment
- Medical device, Lifestyle or therapy programme
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 121 participants
- Where
- 1 siteUnited States
- Study dates
- Jun 2016to 4 Mar 2022
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 55 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- 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.
Show all 9Show fewer
- 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
Who cannot join
- 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
Show all 17Show fewer
- 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)
- Non-correctable vision or hearing problems
- Report of severe depressive symptoms, as indicated by a score greater than 17 on the Patient Health Questionnaire 9-item (PHQ-9).
Trial locations and contacts
1 site in 1 country.
United States1 site
Laureate Institute for Brain Research
Tulsa, Oklahoma, 74008
About this study
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.
Read the detailed description
Generalized anxiety disorder (GAD) is the most common anxiety disorder in primary care, with lifetime prevalence rates of 6%. GAD leads to significant individual and socioeconomic burden (e.g., due to days lost at work and increased health care utilization). Although there is significant comorbidity with major depressive disorder (MDD), a GAD diagnosis conveys a much poorer prognosis, with only 58% with GAD vs. 80% with MDD alone obtaining remission in two years. This highlights the importance of effectively treating GAD, for improving mental and physical health and decreasing socioeconomic burden. First-line treatments include medication (e.g., selective serotonin reuptake inhibitors [SSRIs]) and psychotherapy (e.g., cognitive behavioral therapy [CBT]). While both are superior to placebo, only 40-60% experience significant improvement, with at least 25% relapsing within a year. Thus, long-lasting improvements are occurring in less than 50% of patients. This ineffectiveness has been moderately associated with symptom severity, illness duration, and comorbidity, but these findings do not provide any strategies for improving treatment effectiveness. The current study will seek to identify behavioral or cognitive-affective predictors that indicate how well a patient is responding to treatment so that interventions can be further individualized to more effectively treat refractory patients.
The overall aim of this study are to identify whether neural, biological, and behavioral responses related to the arbitration of conflicting avoidance and approach drives can predict response to Exposure-based versus Behavioral Activate therapy for individuals with generalized anxiety disorder (with or without co-morbid major depressive disorder). This will be accomplished using behavioral, functional magnetic resonance imaging (fMRI), and genetic analyses pre and post Behavioral Activation therapy. Research subjects will include treatment-seeking individuals with clinically significant symptoms of unipolar depression. Diagnosis will be assessed using structured clinical interviews. Anxious and depressive symptom severity, personality characteristics, and general functioning will be collected via self-report paper-and-pencil questionnaires. Objective measures of approach, avoidance, and conflict behavioral responses will be collected using computer-administered testing and related neural responsivity will be measured using fMRI. For exploratory aims, a blood draw will be collect pre and post-treatment to examine genetic factors that may predict response to behavior therapy. This research has the potential to identify neural and behavioral approach-avoidance characteristics that can help predict which patients are likely to respond to Exposure-based versus Behavioral Activation therapy (i.e., predictors of treatment effectiveness) and reveal targets for future treatment modifications.
Aim 1: Examine relationships among approach-avoidance behavior and neural responses, and baseline GAD symptom severity.
Hypothesis 1.1: Approach and conflict arbitration behavior will explain significant variance in baseline symptoms above and beyond avoidance-related behavior.
Hypothesis 1.2: Approach (striatum) and conflict arbitration (lateral PFC) neural activity will explain significant variance in baseline symptoms above and beyond avoidance-related (amygdala) neural activity.
Aim 2: Examine how multi-level approach-avoidance behavior and neural responses predict individualized response to Exposure-based therapy for GAD (compared to Behavioral Activation).
Hypothesis 2.1: Approach-related and conflict arbitration behavior will help predict treatment response above and beyond avoidance-related behavior and baseline symptom severity.
Hypothesis 2.2: Activity in approach-related and conflict arbitration neural circuitry will predict treatment response above and beyond activity in avoidance-related neural circuitry.
Aim 3: Identify the changes in approach-avoidance processes that relate to Exposure therapy elicited functional improvement (compared to Behavioral Activation).
Hypothesis 3.1: The degree to which conflict arbitration abilities increase with treatment will positively relate to functional improvement from pre- to post-treatment.
The statistical analysis plan was described within a protocol paper published in 2020 (Santiago et al., 2020), which is cited in the References section.
- Conditions
- Generalized Anxiety Disorder
- Being tested
- Exposure-based therapy, Behavioral Activation therapy, Computer-based behavioral assessment, Surveys and Interviews, Magnetic resonance imaging (MRI)
- Medical subject headings
- Generalized Anxiety Disorder
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Exposure-based therapyBehavioural
Exposure-based therapy
Behavioral Activation therapyBehavioural
Behavioral Activation therapy
Computer-based behavioral assessmentBehavioural
Computer-based tasks during which participants respond to images on the screen, including abstract images, emotional faces, and pleasant and unpleasant images.
Surveys and InterviewsBehavioural
Surveys and interviews in which participants will be asked to answer questions related to their mental and physical health history and current symptoms.
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).
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).
| Study group | Role | What they receive |
|---|---|---|
| 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). Receives: 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). Receives: Behavioral: Behavioral Activation therapy; Behavioral: Computer-based behavioral assessment; Behavioral: Surveys and Interviews; Device: Magnetic resonance imaging (MRI); Device: Electroencephalography (EEG) |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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.
Test the predictive effects of imaging and behavioral factors on change in symptoms at baseline compared to within 6 weeks after completing treatment. The PROMIS Anxiety Scale yields t-scores, higher scores indicate greater symptom severity, with 50 indicating the population mean and a standard deviation of 10.
Measured: 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.
Test the predictive effects of imaging and behavioral factors on change in symptoms at baseline compared to within 6 weeks after completing treatment. The PROMIS Depression scale yields t-scores; higher scores indicate greater symptom severity, with population mean being 50 and standard deviation of 10.
Measured: 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
Test the predictive effects of imaging and behavioral factors on change in symptoms at baseline compared to within 6 weeks after completing treatment. The Sheehan Disability Scale assesses functional impairment in the domains of work/school, social life, and family life. Participants are provided with a 0-10 visual analog scale with spatiovisual, numeric, and descriptive anchors and asked to rate the extent to which their symptoms have interfered with their functioning on each item for total score ranges of 0-30. Higher scores indicate greater impairment.
Measured: 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
Test the predictive effects of imaging and behavioral factors on post-treatment symptoms (within 6 weeks after completing treatment), covarying for baseline symptom severity. The PSWQ is a 16-item self-report scale designed to measure the trait of worry in adults. Scores range from 16 to 80 with higher scores indicative of higher levels of trait worry. Scores of 66 or greater are thought to indicate clinically significant worry.
Measured: 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.
Test the predictive effects of imaging and behavioral factors on symptoms at post-treatment (within 6 weeks after completing treatment), covarying for baseline symptom severity. The BDI-II is a 21-item questionnaire, with each individual item being rated from 0-3 in a list of four statements arranged in increasing severity about a particular symptom of depression. The outcome measure is the total score on the BDI-II, which is the sum of all 21 items. Higher scores equate to greater severity of depression symptoms. Total score of 0-13 is considered minimal range, 14-19 is mild, 20-28 is moderate, and 29-63 is severe.
Measured: Post- treatment; last time point assessed within 6 weeks following last treatment session, on average at 16 weeks after baseline assessment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Jun 2016 (estimated)
- Study startJun 2016
- Primary completion27 Jul 2021
- Study completion4 Mar 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (9)Papers the sponsor has linked to this study.
- Other trials for Generalized Anxiety DisorderStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 121 participants (actual)
Sponsor and investigators
- Lead sponsor
- Laureate Institute for Brain Research, Inc.
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute of Mental Health (NIMH)
- Responsible party
- Sponsor
- Investigators
- Robin L Aupperle, Ph.D., Principal investigator, Laureate Institute for Brain Research
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02807480
- Sponsor's protocol ID
- 2015-006-02
- Other IDs
- 1K23MH108707-01A1
- Status last verified
- Feb 2024
- First submitted
- 16 Jun 2016
- Last updated
- 26 Mar 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- Individual data sharing
- Yes: Individual participant data may be made available to other individual researchers upon request to the principal investigator, Dr. Robin Aupperle.
Publications
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.
PubMed 24487344Arch 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.
PubMed 23747582Aupperle 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.
PubMed 21319496Aupperle 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.
PubMed 25224633Aupperle 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.
PubMed 21843556Santiago 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.
PubMed 31907032Berg 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.
PubMed 40617801Berg 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.
PubMed 40384942Berg 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.
PubMed 38384390
Study at a glance
From the registry record, last updated by the sponsor on 26 Mar 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Approach-Avoidance Conflict-a Multi-level Predictor for Therapy Response
- ClinicalTrials.gov ID
- NCT02807480
- Acronym / sponsor ID
- 2015-006-02
- Conditions
- Generalized Anxiety Disorder
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 121 participants (actual)
- Lead sponsor
- Laureate Institute for Brain Research, Inc.University, hospital or other
- Collaborators
- National Institute of Mental Health (NIMH)
- Study start
- Jun 2016 (actual)
- Primary completion
- 27 Jul 2021 (actual)
- Study completion
- 4 Mar 2022 (actual)
- First posted
- 21 Jun 2016 (estimated)
- Results
- Posted 26 Mar 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Generalized anxiety disorder (GAD) is the most common anxiety disorder in primary care, with lifetime prevalence rates of 6%. GAD leads to significant individual and socioeconomic burden (e.g., due to days lost at work and increased health care utilization). Although there is significant comorbidity with major depressive disorder (MDD), a GAD diagnosis conveys a much poorer prognosis, with only 58% with GAD vs. 80% with MDD alone obtaining remission in two years. This highlights the importance of effectively treating GAD, for improving mental and physical health and decreasing socioeconomic burden. First-line treatments include medication (e.g., selective serotonin reuptake inhibitors [SSRIs]) and psychotherapy (e.g., cognitive behavioral therapy [CBT]). While both are superior to placebo, only 40-60% experience significant improvement, with at least 25% relapsing within a year. Thus, long-lasting improvements are occurring in less than 50% of patients. This ineffectiveness has been moderately associated with symptom severity, illness duration, and comorbidity, but these findings do not provide any strategies for improving treatment effectiveness. The current study will seek to identify behavioral or cognitive-affective predictors that indicate how well a patient is responding to treatment so that interventions can be further individualized to more effectively treat refractory patients.
The overall aim of this study are to identify whether neural, biological, and behavioral responses related to the arbitration of conflicting avoidance and approach drives can predict response to Exposure-based versus Behavioral Activate therapy for individuals with generalized anxiety disorder (with or without co-morbid major depressive disorder). This will be accomplished using behavioral, functional magnetic resonance imaging (fMRI), and genetic analyses pre and post Behavioral Activation therapy. Research subjects will include treatment-seeking individuals with clinically significant symptoms of unipolar depression. Diagnosis will be assessed using structured clinical interviews. Anxious and depressive symptom severity, personality characteristics, and general functioning will be collected via self-report paper-and-pencil questionnaires. Objective measures of approach, avoidance, and conflict behavioral responses will be collected using computer-administered testing and related neural responsivity will be measured using fMRI. For exploratory aims, a blood draw will be collect pre and post-treatment to examine genetic factors that may predict response to behavior therapy. This research has the potential to identify neural and behavioral approach-avoidance characteristics that can help predict which patients are likely to respond to Exposure-based versus Behavioral Activation therapy (i.e., predictors of treatment effectiveness) and reveal targets for future treatment modifications.
Aim 1: Examine relationships among approach-avoidance behavior and neural responses, and baseline GAD symptom severity.
Hypothesis 1.1: Approach and conflict arbitration behavior will explain significant variance in baseline symptoms above and beyond avoidance-related behavior.
Hypothesis 1.2: Approach (striatum) and conflict arbitration (lateral PFC) neural activity will explain significant variance in baseline symptoms above and beyond avoidance-related (amygdala) neural activity.
Aim 2: Examine how multi-level approach-avoidance behavior and neural responses predict individualized response to Exposure-based therapy for GAD (compared to Behavioral Activation).
Hypothesis 2.1: Approach-related and conflict arbitration behavior will help predict treatment response above and beyond avoidance-related behavior and baseline symptom severity.
Hypothesis 2.2: Activity in approach-related and conflict arbitration neural circuitry will predict treatment response above and beyond activity in avoidance-related neural circuitry.
Aim 3: Identify the changes in approach-avoidance processes that relate to Exposure therapy elicited functional improvement (compared to Behavioral Activation).
Hypothesis 3.1: The degree to which conflict arbitration abilities increase with treatment will positively relate to functional improvement from pre- to post-treatment.
The statistical analysis plan was described within a protocol paper published in 2020 (Santiago et al., 2020), which is cited in the References section.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Exposure-based therapy | Experimental | Behavioral: Exposure-based therapy, Behavioral: Computer-based behavioral assessment, Behavioral: Surveys and Interviews, Device: Magnetic resonance imaging (MRI), Device: Electroencephalography (EEG)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 Activation therapy | Experimental | Behavioral: Behavioral Activation therapy, Behavioral: Computer-based behavioral assessment, Behavioral: Surveys and Interviews, Device: Magnetic resonance imaging (MRI), Device: Electroencephalography (EEG)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). |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (9 listed)
- Age: 18-55
- All genders
- All races
- Eligibility as clinically significant anxiety will be determined by:
- Able to provide written, informed consent
Key exclusion criteria (17 listed)
- 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:
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Exposure-based therapyExposure-based therapy | Behavioural | Exposure-based therapy |
| Behavioral Activation therapyBehavioral Activation therapy | Behavioural | Behavioral Activation therapy |
| Computer-based behavioral assessmentComputer-based tasks during which participants respond to images on the screen, including abstract images, emotional faces, and pleasant and unpleasant images. | Behavioural | Behavioral Activation therapy, Exposure-based therapy |
| Surveys and InterviewsSurveys and interviews in which participants will be asked to answer questions related to their mental and physical health history and current symptoms. | Behavioural | Behavioral Activation therapy, Exposure-based therapy |
| Magnetic resonance imaging (MRI)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). | Device | Behavioral Activation therapy, Exposure-based therapy |
| Electroencephalography (EEG)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). | Device | Behavioral Activation therapy, Exposure-based therapy |
Primary outcome
For Aim1: Baseline Generalized Anxiety Disorder Symptoms as Measured by the Generalized Anxiety Disorder - 7 Item Scale (GAD-7).
Time frame: Baseline assessment (one time point)
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.
For Aims 2 and 3: Change in Generalized Anxiety Disorder Symptoms as Measured by the Generalized Anxiety Disorder - 7 Item Scale (GAD-7).
Time frame: 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.
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.
5 secondary outcomes
Change in Anxiety Symptoms as Measured by the Patient Reported Outcomes Measurement Information System (PROMIS) Anxiety Scale.
Time frame: 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.
Time frame: 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
Time frame: 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
Time frame: 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.
Time frame: Post- treatment; last time point assessed within 6 weeks following last treatment session, on average at 16 weeks after baseline assessment
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Mar 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 24487344Cuijpers 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.
- Background: PubMed 23747582Arch 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.
- Background: PubMed 21319496Aupperle 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.
- Background: PubMed 25224633Aupperle 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.
- Background: PubMed 21843556Aupperle 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.
- Background: PubMed 31907032Santiago 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.
- Derived from this study: PubMed 40617801Berg 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.
- Derived from this study: PubMed 40384942Berg 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.
- Derived from this study: PubMed 38384390Berg 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.
- Individual participant dataSharing planned: Yes. Individual participant data may be made available to other individual researchers upon request to the principal investigator, Dr. Robin Aupperle.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Robin L Aupperle, Ph.D. principal investigator
Laureate Institute for Brain Research
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Exposure-based therapy, Behavioral Activation therapy and Computer-based behavioral assessment in people with Generalized Anxiety Disorder, run by Laureate Institute for Brain Research, Inc. at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 26 Mar 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 26 Mar 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
For Aim1: Baseline Generalized Anxiety Disorder Symptoms as Measured by the Generalized Anxiety Disorder - 7 Item Scale (GAD-7). (time frame: Baseline assessment (one time point)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02807480, which also lists 9 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Mar 2024.