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

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ClinicalTrials.gov Identifier: NCT02807480
Recruitment Status : Recruiting
First Posted : June 21, 2016
Last Update Posted : February 15, 2019
Sponsor:
Collaborator:
National Institute of Mental Health (NIMH)
Information provided by (Responsible Party):
Laureate Institute for Brain Research, Inc.

Tracking Information
First Submitted Date  ICMJE June 16, 2016
First Posted Date  ICMJE June 21, 2016
Last Update Posted Date February 15, 2019
Study Start Date  ICMJE June 2016
Estimated Primary Completion Date April 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 20, 2016)
  • 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.
  • 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.
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT02807480 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: June 20, 2016)
  • 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 ]
    Test the predictive effects of imaging and behavioral factors on change in symptoms at baseline compared to within 6 weeks after completing treatment.
  • 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 ]
    Test the predictive effects of imaging and behavioral factors on change in symptoms at baseline compared to within 6 weeks after completing treatment.
  • 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 ]
    Test the predictive effects of imaging and behavioral factors on change in symptoms at baseline compared to within 6 weeks after completing treatment.
  • Change in depressive symptoms as measured by the Beck Depression Inventory - II. [ Time Frame: 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.
  • Change in worry symptoms as measured by the Penn State Worry Questionnaire. [ Time Frame: 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.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Approach-Avoidance Conflict-a Multi-level Predictor for Therapy Response
Official Title  ICMJE Approach-Avoidance Conflict-a Multi-level Predictor for Therapy Response
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.
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
Condition  ICMJE Generalized Anxiety Disorder
Intervention  ICMJE
  • Behavioral: Exposure-based therapy
    Exposure-based therapy
  • Behavioral: Behavioral Activation therapy
    Behavioral Activation therapy
  • Behavioral: Computer-based behavioral assessment
    Computer-based tasks during which participants respond to images on the screen, including abstract images, emotional faces, and pleasant and unpleasant images.
  • Behavioral: Surveys and Interviews
    Surveys and interviews in which participants will be asked to answer questions related to their mental and physical health history and current symptoms.
  • Device: 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: 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).
Study Arms  ICMJE
  • Experimental: Exposure-based therapy
    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).
    Interventions:
    • Behavioral: Exposure-based therapy
    • Behavioral: Computer-based behavioral assessment
    • Behavioral: Surveys and Interviews
    • Device: Magnetic resonance imaging (MRI)
    • Device: Electroencephalography (EEG)
  • Experimental: Behavioral Activation therapy
    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).
    Interventions:
    • Behavioral: Behavioral Activation therapy
    • Behavioral: Computer-based behavioral assessment
    • Behavioral: Surveys and Interviews
    • Device: Magnetic resonance imaging (MRI)
    • Device: Electroencephalography (EEG)
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: June 20, 2016)
100
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE April 2021
Estimated Primary Completion Date April 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Age: 18-55
  2. All genders
  3. All races
  4. 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.
  5. Able to provide written, informed consent
  6. Have sufficient proficiency in English language to understand and complete interviews, questionnaires, and all other study procedures

Exclusion Criteria:

  1. 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.
  2. A history of drug or alcohol abuse in the past 6 months,
  3. 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
  4. 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.
  5. Active suicidal ideation with intent or plan
  6. 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.
  7. Prescription of a medication outside of the accepted range, as determined by the best clinical practices and current research
  8. Taking drugs that affect the fMRI hemodynamic response.
  9. 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
  10. 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)
  11. Non-correctable vision or hearing problems
  12. Report of severe depressive symptoms, as indicated by a score greater than 17 on the Patient Health Questionnaire 9-item (PHQ-9).
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 55 Years   (Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Robin Aupperle, PhD 918-502-5155 neurocatt@laureateinstitute.org
Contact: Robin L Aupperle, Ph.D. 918-502-5744 raupperle@laureateinstitute.org
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02807480
Other Study ID Numbers  ICMJE 2015-006-02
1K23MH108707-01A1 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Responsible Party Laureate Institute for Brain Research, Inc.
Study Sponsor  ICMJE Laureate Institute for Brain Research, Inc.
Collaborators  ICMJE National Institute of Mental Health (NIMH)
Investigators  ICMJE
Principal Investigator: Robin L Aupperle, Ph.D. Laureate Institute for Brain Research
PRS Account Laureate Institute for Brain Research, Inc.
Verification Date February 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP