Neural Mechanisms of Treatment Response to ADAPT

Study Overview
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Brief Summary
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Complex functional abdominal pain disorders (FAPD) with co-occurring anxiety are highly prevalent in children, can be very disabling, and are not responsive to currently available treatments. This research aims to better understand the neural mechanisms involved in a promising nonpharmacological treatment for FAPD to ultimately guide the development of more targeted treatment approaches for afflicted youth.

Detailed Description
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Functional abdominal pain disorders (FAPD) are among the most common chronic pain conditions of childhood and are associated with significant functional disability, pain, and comorbid anxiety that adversely impacts treatment outcomes. Thus, the PI developed a psychological intervention, Aim to Decrease Anxiety and Pain Treatment (ADAPT; F32HD078049), that targets both pain and anxiety using cognitive behavioral therapy and mindfulness meditation approaches to improve patient outcomes. Preliminary testing has shown that ADAPT reduces pain and anxiety in youth with FAPD. In this study, brain mechanisms implicated in the modulation of pain and response to ADAPT will be investigated. Participants with FAPD and comorbid anxiety will be randomized to either ADAPT or a waitlist control (each condition will last for approximately 6 weeks). Participants will undergo fMRIs to explore changes in functional connectivity and regional brain activation during visceral pain induction (via the water load symptom provocation task; WL-SPT). In Aim 1, functional connectivity patterns associated with a subjective response to pain induction in youth with FAPD who receive ADAPT will be compared to the waitlist control. Conventional blood oxygenation level dependent (BOLD) fMRI will be used to assess functional connectivity to capture moment-to-moment fluctuations in activity. In Aim 2, changes in regional brain activation for those receiving ADAPT will be compared to those in the waitlist condition. The novel arterial spin label (ASL) MRI technique will be used to gain inferences into regional brain activity. In line with the NCCIH funding priorities, this study seeks to increase understanding of the mechanisms through which mind and body approaches impact clinical outcomes in chronic pain and anxiety. Results will advance the field by providing crucial information needed for the refinement and testing of a tailored mind body intervention for FAPD and comorbid anxiety.

Official Title
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Using fMRI to Understand Response to an Integrative Treatment for Pain and Anxiety in Pediatric Functional Abdominal Pain Disorders (FAPD)

Conditions
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Functional Abdominal Pain Syndrome, Anxiety

Intervention / Treatment
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* Behavioral: ADAPT


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria Children (boys and girls) between 11 and 16 years of age and their parent/primary caregiver. Meets criteria for FAPD based on physician diagnosis of FAPD and ROME IV FAPD criteria Meets criteria for presence of clinically significant anxiety (based on the Generalized Anxiety Disorders-7 [GAD-7] cut-off score ≥10). Sufficient English language ability necessary to complete study measures and protocol. Exclusion Criteria Children with significant medical condition(s) with an identifiable organic cause including those that may include abdominal pain symptoms (e.g., Inflammatory Bowel Diseases). Children with a documented developmental delays, autism spectrum disorder, a previously diagnosed thought disorder (i.e., psychosis), or bipolar disorder. Significant visual, hearing, or speech impairment. Organic brain injury. Participants who are currently in psychological therapy for pain or anxiety. Participants with severe depressive symptoms (cut-score ≥20) on the Patient Health Questionnaire 9 [PHQ-9] or active suicidal ideation. Exclusionary criteria specific to the fMRI component of the study: Participants with an implant such as a cochlear implant device, a pacemaker or neurostimulator containing electrical circuitry or generating magnetic signals. Participants with any significant ferrous material in their body that could pose the potential for harm in the fMRI environment or cause signal suppression of key regions (i.e. orthodontia). Female participants who report current/suspected pregnancy. Participants with evidence of claustrophobia.

Ages Eligible for Study
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Minimum Age: 11 Years
Maximum Age: 16 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ADAPT<br>Participants randomized to ADAPT will complete Aim to Decrease Anxiety and Pain Treatment (ADAPT), a remotely delivered tailored intervention that integrates mindfulness meditation with cognitive behavioral therapy. It consists of 6 sessions and blends pain and anxiety coping strategies. The first 2 sessions are interactive with a trained psychological provider and the following 4 sessions are web-based. Each web-based session is followed by therapist support. | Behavioral: ADAPT<br>* Aim to Decrease Anxiety and Pain Treatment is a remotely delivered tailored treatment integrating mindfulness meditation and cognitive behavioral therapy. It consists of 6 sessions and blends pain and anxiety coping strategies. The first 2 sessions will be interactive with a trained psychological provider and the following 4 sessions will be web-based. Each web-based session will be followed by therapist support. The intervention is delivered through a HIPAA compliant video platform.<br>|
| No Intervention: Waitlist Control<br>Participants randomized to waitlist control will receive medical treatment as usual. These participants will be given the opportunity to complete ADAPT upon completion of the post assessment. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Functional Connectivity of Amygdala with the Prefrontal Cortex | Changes in functional connectivity will be examined using the Blood Oxygenation Level Dependent (BOLD) effect | through study completion, an average of 9 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Regional Brain Activation in Areas Associated with Cognitive, Affective, and Visceral Afferent Aspects of Pain | Changes in regional brain activity will be assessed by arterial spin labeling (ASL) | through study completion, an average of 9 weeks | 
| Neuroimaging data linked to pain and anxiety outcomes | Changes in functional connectivity/regional brain activation will correspond with changes in pain and anxiety | through study completion, an average of 9 weeks | 
| Pain Intensity/Unpleasantness via Visual Analog Scale | State pain intensity and unpleasantness levels using a 0 - 10 scale | through study completion, an average of 9 weeks | 
| State Anxiety | 0 - 10 self-report of how anxious the child is feeling in the present moment | through study completion, an average of 9 weeks | 
| Screen for Child Anxiety Related Disorders | Patient-reported measure of anxiety symptoms over the past 3 months | through study completion, an average of 9 weeks | 
| Generalized Anxiety Disorders 7 (GAD-7) | Patient-reported measure of anxiety symptoms over the past 2 weeks. Measures contains 7 items measured on a scale of 0-21 with higher scores indicating greater anxiety. | through study completion, an average of 9 weeks | 
| Functional Disability Inventory | A 15-item self report inventory measuring perceived pain-related disability | through study completion, an average of 9 weeks | 
| Rome IV Diagnosis Checklist | Physician reported FAPD criteria (based on the Rome IV) met by the patient | at screening to determine eligibility | 
| MRI Safety and Screening | Utilized to determine if patient can safely complete fMRI protocol | at screening to determine eligibility | 
| Self-Efficacy Pain Scale- Child Version | Measure of child self-efficacy when in pain | through study completion, an average of 9 weeks | 
| Affective Reactivity Index- Self Report | 7-item measure of emotional regulation | through study completion, an average of 9 weeks | 
| Pain Catastrophizing Scale for Children | Maladaptive beliefs about pain and long-term processes | through study completion, an average of 9 weeks | 
| Children's Depression Inventory 2 | A measure of depressive symptoms in the past 2 weeks | through study completion, an average of 9 weeks | 
| Patient Health Questionnaire 9 | A 9-item measure of depressive symptoms in the past 2 weeks. Scores range from 0-27 with higher scores indicating greater depressive symptoms. | through study completion, an average of 9 weeks | 
| NIH Promis Pain Interference | Measure of functional impairment due to pediatric pain | through study completion, an average of 9 weeks | 
| Peterson Pubertal Development Scale | Pubertal status assessed via clinical interview | through study completion, an average of 9 weeks | 
| Edinburgh Handedness Inventory | To assess the dominance of a person's right or left hand in everyday activities; one item was removed (striking a match) because it is not appropriate for children | through study completion, an average of 9 weeks | 
| Fullness Rating Scale | Youth will use scale to indicate how full they feel before and after water ingestion | through study completion, an average of 9 weeks | 
| Child Pain History | Demographic factors, school absences, and pain duration, location, etc via caregiver report | through study completion, an average of 9 weeks | 
| Depression Anxiety Stress Scales | Measure of caregiver depression, anxiety, and tension/stress. | through study completion, an average of 9 weeks | 
| Pain Catastrophizing Scale | Maladaptive beliefs about pain and long-term outcomes completed by caregiver | through study completion, an average of 9 weeks | 
| Screen for Child Anxiety Related Disorders- Parent Report | Parent-reported child anxiety symptoms over the past three months; ≥25 is clinical anxiety | through study completion, an average of 9 weeks | 
| Functional Disability Inventory- Parent Report | Parent-reported child anxiety symptoms over the past three months; ≥25 is clinical anxiety | through study completion, an average of 9 weeks | 
| Self-Efficacy Chronic Pain Scale- Parent Version | Parent reported child self-efficacy during pain | through study completion, an average of 9 weeks | 
| Medication use | current medication use will be obtained via medical chart review and parent report | through study completion, an average of 9 weeks | 
| Affective Reactivity Index- Parent- Report | 7-item measure of child emotional regulation | through study completion, an average of 9 weeks | 
| Adverse Childhood Events (ACEs) | A 9-item query for frequency of adverse events experienced during childhood. Frequency count ranges from 0-9 with a higher score indicating a greater number of adverse childhood events. | through study completion, an average of 9 weeks | 
| COVID-19 Exposure and Family Impact Survey (CEFIS) | 38-item measure of COVID-19 related distress and impact on families and caregivers. Part 1 of the measure queries the frequency of COVID-related events on a scale of 0-25 with higher scores indicating a greater number of experienced events. Part 2 of the measures the adverse impact of COVID-related events and has a score range of 12-60 with higher scores indicating a greater adverse impact. | through study completion, an average of 9 weeks | 
| Child COVID-19 Related Distress | A visual analog scale item assessing for the child's COVID-related distress on a scale of 0-10. A greater score indicates greater distress. | through study completion, an average of 9 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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cognitive behavioral therapy, mindfulness meditation, fMRI, neuroimaging