Feelings and Body Investigators (FBI)

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R-21 Phase

The Feelings and Body Investigators (FBI): Interoceptive Exposure for Child Abdominal Pain proposes to develop (R21) an acceptance-based behavioral treatment intervention for children 5 through 9 years old with impairing functional abdominal pain. Functional abdominal pain (FAP) is a frequent somatic complaint in young children (approximately 10% of those presenting to primary care) and is responsible for distress in the afflicted child and the family; unnecessary health care utilization and cost; and interference with schooling. Further, FAP is predictive of future pain disorders, psychiatric disorders, and impairment. Despite this prevalent and significant burden, there are currently no accepted successful treatments for FAP in young children.

The objective of this proposal is to develop an intervention for FAP based on fundamental research on aberrant neurodevelopment of the gut-brain axis and subsequent modification by the social environment. In brief, this work suggests that FAP results from the influence of pain on the neurodevelopment of the gut-brain axis. The gut-brain axis maintains the body’s homeostasis, encompassing capacities to sense changes in the viscera and respond adaptively (e.g., responding to gut pangs of hunger). Healthy maturation of the gut-brain axis is crucial for the emergence of weight and emotion regulation. Further, the interpretation of visceral signals has a developmental course, as children learn how to identify, label, and describe body sensations; e.g., whether gut sensations are butterflies of anxiety or gut pain. FAP represents a disruption of this normal developmental course. FAP may also be exacerbated by environmental influences (e.g., extensive medical diagnostic testing) that increase parents’ health anxiety and their children’s fear and distrust of their bodies. We propose to intervene directly early in development on these aberrations in gut-brain maturation by training eligible child-caregiver dyads to be feelings and body (FBI) investigators using interoceptive exposure (the manipulation of visceral sensation) to explore a “body mystery” in a playful, investigative context designed to increase curiosity about body function. Sessions are conducted in clinic and home (via web-camera) to facilitate generalization.

Because of limited sample size and the iterative nature of intervention development, criteria for success at the R21 Phase are based primarily on clinical rather than statistical criteria. We have established goals for compliance, completion, and reduction in physical and psychological distress aimed at establishing the feasibility and efficacy of the intervention. We carefully considered statistical constraints of pilot investigations by framing outcomes based on clinical but not statistical significance.

There are no known physical risks to the child or parent associated with this proposed study.

There are minimal risks such as feeling uncomfortable answering questions.

Recruitment Sampling Frame: The primary care clinic where we will recruit sees both privately insured and Medicaid children. The staff saw 1798 children between the ages of 5 and 9 years old in a previous study conducted at this clinic, The Preschool Anxiety Study. Based on our preschool cohort data (n=918) drawn from this primary care clinic, we expect 1) 8% to meet study criteria or 144 children. Assuming that 20% refuse to screen (approximately 30), we plan to screen 174 children. We need to recruit 26 individuals for phase 1 and phase 2 of the R21 and it will take us 18 weeks. Further, based on our cohort data, we expect roughly equal numbers of males, females, ages, and those with a psychiatric disorder. We also found that the racial distribution of abdominal pain is roughly equivalent to the racial and ethnic distribution of the Raleigh/Durham metropolitan region (45% Caucasian, 45% African-American, and 10% other underrepresented minorities). Thus, we are able to recruit a representative sample and make the intervention available to all who would benefit.

Treatment Procedures/Quality Control for R21

Treatment Procedures: Treatment sessions will be conducted in the Duke Young Child Laboratory (see below). For home-based sessions, we use web-cameras so the participants can practice new skills at home to facilitate generalization. All families will be given a web-camera, if needed, for this purpose. As with all procedures, children lead the sessions (the “FBI missions”) both to maximize their engagement and minimize their fears of body-focused exposures. While part of the treatment is gently nudging children to do things that produce a somatic sensation, yet it is critical that children feel safe and thus they can terminate a session whenever they wish. Our typical approach to such a request is to first attempt to titrate the exposure down to a level that is acceptable for the children until they are excited about the mission. In the event of continued refusal, we use the session to hone our “observational skills” or go into “investigative mode” figuring out why today is such a rough day. Thus, sessions are always productive – no matter what the emotional state of the child, but yet always sensitive to the needs of the child.

Assessment Procedures

Four separate assessment types occur throughout the study:

  1. a) 7 days of daily pain diaries (approximately 15 minutes per day)
  2. b) Parent and child-completed surveys (approximately 1 hour)
  3. c) Parent interview (approximately 3 hours)
  4. d) Laboratory mood induction task (approximately 1 hour)

All laboratory assessments (and some treatment sessions) will be conducted in our Duke Young Child Laboratory in the Center for Developmental Epidemiology, located on bus lines including free public bus lines with free parking and available childcare. The laboratory consists of a cheerful playroom where children can use toys and a comfortable interviewing room (adjacent to playroom) where parents will be interviewed (c) and children will complete the laboratory mood induction task (d). Parents will be able to use seating in the playroom during the mood induction task to complete the surveys (b).

The daily pain diaries (a) will be given to participants to fill out where ever works best for the participants. They will be given these three daily surveys to fill out, within a paper flip booklet which the subject will turn in to the researchers after the completing the Daily Pain Diaries.

We also send out a short questionnaire to our subject’s teachers at two time points (which we are currently getting permission to do within our main study consent form that the parent fills out and signs, along with giving us the teachers name, school, address, e-mail address, and phone number).  First we plan to contact the subject’s teacher via e-mail to see if they would be willing to fill out these questionnaires, and if they e-mail us back, letting us know that they would like to participate, we will send the teacher a questionnaire link, via Duke Qualtrics, prior to the subject starting their investigational treatment sessions.  We would then e-mail the teacher a second time, after the subject has completed all 10 of the treatment sessions, to see if they would be willing to again fill out these questions via a Duke Qualtrics link.

Assessment Measures:

Feasibility: Hypotheses A.H2a, A.H2b/B.H1a, B.H1b.

We will keep a continuous measure of session attendance with missed sessions that are rescheduled within a two-week window (to account for vacations, etc.). Homework practice is recorded by therapists at every session (number of practice sessions completed regardless of degree of completion) and quality of homework (none, attempt, completed) to provide a continuous measure of treatment feasibility.

Clinical Significance: Hypotheses A.H3a /B.H3a, B.H3b, B.H3c, B.H3d

Treatment efficacy is assessed along dimensions of: a) physical pain, b) impairment, and c) emotion-regulation (exploratory).

Pain: Children and their caregivers will be trained to complete pain ratings using a Daily Pain Diary which contains a Pain Thermometer to rate pain experienced and the Self-Assessment Manikin (SAM) scale to rate emotional experience. Caregivers are trained to use the child’s verbal reports, facial expressions, and behaviors to make these ratings. Children make their ratings twice daily: in the morning and before dinner. Parents rate their child’s pain three times daily: in the morning, before dinner, and at the end of the day. The end of day survey contains additional questions asking about the child’s overall pain experience throughout the entire day, as well as their distress and mood. These ratings are completed for one week prior to treatment and one week post-treatment, on a daily basis. Pain ratings are collected during 2 of the 10 weeks of treatment.

Impairment: Change in function will be assessed by diagnostic interviews and global ratings of clinical and functional change by reviewers blind to the randomization on the basis of these interviews, functional status as reported in pain/emotion diaries, and medical chart review of frequency of visits and physician contacts.

Diagnostic Interviews: Dr. Helen Egger is the leading author of the Preschool Age Psychiatric Assessment (PAPA), one of the most widely used and reliable semi-structured interviews for diagnosis of young child psychopathology. The caregiver reports on his or her child’s family context, psychiatric diagnosis, self-regulatory abilities including sensitivity to sensation, developmental history, and impairment. Numerous studies have established its predictive validity and sensitivity to change with intervention. Impairment is assessed across multiple domains as well as the perceived cause of impairment (e.g. due to physical symptoms). To shorten administration, modules chosen are based on frequency of somatic symptoms and include ADHD, somatization, social phobia, separation anxiety, generalized anxiety, and depression.

Functioning ratings in daily pain diaries – Parents are asked to provide an assessment of their child’s functioning three times per day. In the morning (beginning of day) and afternoon (before dinner), they rate their child’s ability to pay attention and have fun whilst experiencing tummy pain. At the end of the day, they provide a detailed report of their child’s physical and emotional functioning over the course of the day.

Global Ratings: Clinical Response – At pre and post-assessment, clinical status and improvement will be rated by blind raters on the eight-point Clinical Global Impression Scale Improvement. Participants who are rated as clinically improved or much improved in the area of physical symptoms will be considered treatment responders.

Global Ratings: Functioning – Global functioning will be rated by a rater blind to treatment status using the Children’s Global Assessment Scale, a 100-point scale with 1 being most impaired and 100 being least impaired. A score of 41–50 indicates a moderate degree of interference in functioning in most social areas or severe impairment of functioning in one area, whereas a score of 61–70 indicates generally functioning well with some difficulty in a single area. Scores of 70 or above will be considered responders.

Emotion Regulation: Emotion regulation is measured at pre- and post-treatment with our mood induction paradigm and child-reported emotional valence ratings in the daily pain diaries.

Mood induction laboratory paradigm – We employ a standardized mood induction paradigm for young children (viewing film clips). Additionally, we have children self-report on their emotions, pain, and hunger level, as well as changes in body sensation (movement of their heart and gut), throughout the task. Figure 4 provides a graphical representation of the mood induction task. To better assess the subject’s physiological state while watching these mood inducing video clips, subjects will be hooked up to a BioPac machine which will collect the following physiological data:  EEG, ECG, Galvanic Skin Response, and Respiration. The film clips include exciting clips,, sad clips, disgusting clips, fearful clips, and happy clips. If children have successfully learned to discriminate and regulate emotional experiences, they should 1) complete the lab task despite increased emotion, 2) change ratings of body sensation and emotion with each clip, but not pain
Child-reported emotional valence – We have children use the SAM scale in their daily pain diaries to assess their daily emotional state. By giving daily ratings of their emotional state, their pain state, and combining these with parent reports of the same, we can examine increasing segregation of ratings of pain from those of emotional experience.

Statistical Methods

Tests of hypotheses will be based on standard binomial models for proportions and Student’s t-test or standard ANCOVA regression models as appropriate for continuous measures; ordinal data not meeting assumptions of normality will be analyzed using nonparametric Wilcoxon Mann-Whitney procedures or, in some cases, generalized linear regression (Poisson, logistic) models. For the R33, evaluations will be repeated 6-months post-treatment.

Compensation for FBI Study Participants: The parent and child will be compensated up to $380 for their participation in the study. The parent will receive $5 a day for each day that they complete all 3 of the Daily Pain Diaries, up to $35 for the 1st week of Daily Pain Diaries (pre-treatment) and up to another $35 for the 2nd week of Daily Pain Diaries (post treatment). The parent will also receive $40 for the first mood induction laboratory assessment, and $100 for the second mood induction laboratory assessment. Finally, the parent will receive $35 for each of the parent-interviews (ePAPAs) that they complete (one pre-treatment and one post-treatment). Children will receive a prize at the end of each assessment. No monetary compensation will be provided for the 10 intervention sessions, but children will be given an assortment of toys at the end of each in-person session.

R-33 Phase

As of February 2016, we have completed the R-21 phase of The Feeling and Body Investigators (FBI) Study (N=26) and have received approval to continue into the R-33 phase of the study.  We are currently in the process of analyzing the data collected during the R-21 phase of the study, updating materials based on subject feedback, and preparing to begin recruitment of our next 100 subjects (N=100).

The R-33 phase, called The Duke Tummy Pain (DTP) Study, will differ from the R-21 phase in that we will be comparing our Investigational Treatment (Feeling and Body Investigator Treatment, or FBI) to a control treatment (Caregivers in Action Treatment, or CIA). Recruitment, eligibility criteria, and assessment strategies will stay the same as they were in the R-21 phase.  Subjects recruited into the R-33 phase will be randomized to either the experimental treatment (FBI) or the control treatment (CIA), but both groups will receive the same number of treatment sessions (10), with 8 sessions conducted in our lab space and 2 sessions conducted via Skype.

The R33 period will repeat the goals of the R21 period using an improved intervention, a large sample to discern statistical and clinical significance, and a randomized design with a parent-psychoeducation comparison condition. Endpoints include quantification of whether this intervention can have broad impact: using primary care practices to screen and subsequently treat abdominal pain early in the life and disorder cycle.

Those who receive the FBI Investigational Treatment will still be trained using an improved version of the FBI R-21’s interoceptive exposure (the manipulation of visceral sensation) to explore “body mysteries” in a playful, investigative context, designed to increase curiosity about body functions.  The CIA (treatment as usual) focuses more on the parent, who will receive a psychoeducation comparison condition. Parents will receive educational handouts, similar to what they would receive from a Pediatricians office, and the therapist will review these materials with the parent, while the child is playing in the room.

As of November 2016, Dr. Helen Egger (a Co-PI on this study) has taken a position at NYU and will no longer be working with subject’s PHI for this study.  Helen will now be moved to our “Outside Duke Key Personnel” and is still involved with Duke, but as an adjunct professor.

Lastly, as of January of 2018 we plan to add a small group of 10-year-old children, N=10, as a pilot, to test our investigational therapy on an older age group.

Recruitment Sampling Frame: The primary care clinic where we recruited during the R-21 sees both privately insured and Medicaid children. The staff saw 1798 children between the ages of 5 and 9 years old in a previous study conducted at this clinic, The Preschool Anxiety Study. Based on our preschool cohort data (n=918) drawn from this primary care clinic, we expect 1) 8% to meet study criteria or 144 children. Assuming that 20% refuse to screen (approximately 30), we plan to screen 174 children. We need to recruit 26 individuals for phase 1 and phase 2 of the R21 and it will take us 18 weeks.  For the R33, we need to recruit 140 individuals to enroll 100 subjects; it will take 70 weeks to recruit this number (1.3 years). To get our N of 100 we plan to “consent to screen” close to 2,000 potential subjects. Having found that we had recruited most of the eligible subjects from the Picket Road Pediatric Clinic during the R-21 phase, we began recruiting from Duke’s Southpoint Pediatric Clinic as well in late 2015.  For the R-33 phase we plan to recruit from Duke’s Southpoint Clinic, Durham Pediatrics, and potentially at Picket Road Pediatric Clinic once additional potential subjects have aged in. Further, based on our cohort data, we expect roughly equal numbers of males, females, ages, and those with a psychiatric disorder. We also found that the racial distribution of abdominal pain is roughly equivalent to the racial and ethnic distribution of the Raleigh/Durham metropolitan region (45% Caucasian, 45% African-American, and 10% other underrepresented minorities). Thus, we are able to recruit a representative sample and make the intervention available to all who would benefit.

Assignment to Study Group

For the R33 caregiver-child dyads will be randomized into one of two potential treatment groups:  1) Feeling and Body Investigators (FBI)- A child focused treatment, or 2) Caregivers In Action (CIA)- a parent focused treatment.  Participants who refuse the study at the baseline encounter will also be entered into the tracking database to track characteristics of refusals.

Treatment Procedures/Quality Control for R-33

Treatment Procedures: Treatment sessions will be conducted either in the Duke Young Child Laboratory (see below) or in the Duke Center for Eating Disorders at Lakeview East. For home-based sessions, we use web-cameras so the participants can practice new skills at home to facilitate generalization. All families will be given a web-camera, if needed, for this purpose.

Those Assigned to FBI: Children will lead the sessions (the “FBI missions”) both to maximize their engagement and minimize their fears of body-focused exposures. While part of the treatment is gently nudging children to do things that produce a somatic sensation, it is critical that children feel safe and thus they can terminate a session whenever they wish. Our typical approach to such a request is to first attempt to titrate the exposure down to a level that is acceptable for the children until they are excited about the mission. In the event of continued refusal, we use the session to hone our “observational skills” or go into “investigative mode”: figuring out why today is such a rough day. Thus, sessions are always productive no matter what the emotional state of the child.

Those Assigned to CIA:  These sessions will be focused on the psychoeducation of the parent, but the child will be in the room playing while the therapist is reviewing the educational materials with the parent. There will be a 10-lesson educational curriculum designed to educate caregivers about the management of their child with FAP.  To create the curriculum for CIA, we reviewed patient handouts for exemplary pediatric gastrointestinal programs, professional healthcare organizations, and companies that supply the patient handouts incorporated into electronic medical record systems (e.g. Maestro). Following the review of these materials, we extracted the primary themes and lessons and organized them into a session-by-session curricula.

Assessment Procedures

**The same as the R-21 Phase, except for adding a 6 month follow up battery of questionnaires which will be sent to the parent via an e-mail link using Duke Qualtrics.  These questionnaires will be the same as the questionnaires that caregivers fill out during the Lab 1 and Lab 2 portion of this study.

Assessment Measures:

Feasibility: Hypotheses A.H2a, A.H2b/B.H1a, B.H1b.

We will keep a continuous measure of session attendance with missed sessions that are rescheduled within a two-week window (to account for vacations, etc.) counted (range: 0-10). Homework practice is recorded by therapists at every session and rated by two independent blind raters on frequency (number of practice sessions completed regardless of degree of completion) and quality of homework (none, attempt, completed) to provide a continuous measure of treatment feasibility.

Clinical Significance: Hypotheses A.H3a /B.H3a, B.H3b, B.H3c, B.H3d

Treatment efficacy is assessed along dimensions of: a) physical pain, b) impairment, and c) emotion-regulation (exploratory).

**All assessments will be the same as in the R-21 Phase**

 Statistical Methods

**The same as the R-21 Phase**

Compensation for FBI Study Participants: **The same as the R-21 Phase except, the parent will receive a $30 Amazon gift card for completing a final 6 month follow-up survey.**

Compensation for FBI Study Participants: The parent and child will be compensated up to $310 for their participation in the study. The parent will receive $5 a day for each day that they complete all 3 of the Daily Pain Diaries, up to $35 for the 1st week of Daily Pain Diaries (pre-treatment) and up to another $35 for the 2nd week of Daily Pain Diaries (post treatment). The parent will also receive $40 for the first mood induction laboratory assessment, and $100 for the second mood induction laboratory assessment. The parent will receive $35 for each of the parent-interviews (ePAPAs) that they complete (one pre-treatment and one post-treatment) and finally, they will receive a $30 gift card for completing the 6 month follow-up questionnaires.  Children will receive a prize at the end of each assessment  No monetary compensation will be provided for the 10 intervention sessions, but children will be given an assortment of toys at the end of each in-person session.

At study conclusion, we will have developed and provided preliminary evaluation of a novel intervention for FAP in young children—a condition for which there are currently no accepted, successful treatments. In doing so, we will have translated basic research in the neurodevelopment of the gut-brain axis into an innovative treatment program. We intend for the timing, content, and intervention strategy to not only improve function, but also to alter trajectories of risk for the development of psychosomatic and pain disorders later in life, thereby providing primary care practices with a feasible solution to the issue of childhood abdominal pain.