Shifting Perspectives R33 Phase: Enhancing Outcomes in Anorexia Nervosa With CRT

• ClinicalTrials.gov Identifier: NCT05017831
• Recruitment Status: Recruiting
• First Posted: August 24, 2021
• Last Update Posted: January 6, 2023
• Sponsor: Children's Hospital of Philadelphia
• Collaborator: National Institute of Mental Health (NIMH)
• Information provided by (Responsible Party): Children's Hospital of Philadelphia

Study Description

Brief Summary:

Anorexia Nervosa is a serious life-threatening illness with a typical age of onset in adolescence; if not effectively treated, it has the potential to significantly impact adolescent development and quality of life. Research on executive functioning in anorexia nervosa indicates that it may be a viable target for intervention that could improve outcome. The current project focuses on determining whether or not the investigators can improve set-shifting in affected adolescents in the hopes that improvements in set-shifting will, ultimately, improve outcome.

Condition or disease	Intervention/treatment	Phase
Anorexia Nervosa	Behavioral: Family Based Treatment; Behavioral: Cognitive Remediation Therapy	Not Applicable

Detailed Description:

This is the second phase (R33) of a two-phased project exploring the effect of adding Cognitive Remediation Therapy (CRT) to traditional Family Based Treatment (FBT) for adolescents with Anorexia Nervosa (AN) and their families. This phase (R33) follows a prior 2-year study (R61) which examined the impact of CRT on set-shifting abilities (a type of executive functioning often referred to as cognitive flexibility). This second phase aims to replicate findings from the first study as well as examine whether the addition of CRT to traditional FBT will impact treatment outcomes (e.g., eating disorder symptoms, weight outcomes). CRT is an adjunctive treatment approach where adolescents learn different ways of thinking and problem solving to become more flexible thinkers. The investigators will recruit and randomly assign 96 families of youth with AN to either an FBT group or FBT with adolescent-focused CRT group. Parents and adolescents will complete questionnaires and assessments to evaluate outcomes and predictors of outcome. Evidence supporting FBT+CRT to increase set-shifting in adolescents will inform future efforts to leverage understanding of neurobiology of AN in adolescents to improve outcome. Results will also inform how best to augment current treatments, support parents, and increase positive outcomes for adolescents with AN, and reduce relapse.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 96 participants
• Allocation: Randomized
• Intervention Model: Factorial Assignment
• Intervention Model Description: Random assignment to one of two groups.
• Masking: Single (Outcomes Assessor)
• Masking Description: Any study team member who is assessing for outcomes will not know which participant/family is in which group.
• Primary Purpose: Treatment
• Official Title: Shifting Perspectives R33 Phase: Enhancing Outcomes in Adolescent Anorexia Nervosa With Cognitive Remediation Therapy (CRT)
• Actual Study Start Date: November 5, 2021
• Estimated Primary Completion Date: August 15, 2024
• Estimated Study Completion Date: August 15, 2024

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: Family Based Treatment (FBT); Families will receive 15 sessions of FBT alone.	Behavioral: Family Based Treatment; Family Based Treatment (FBT) is an evidence based treatment in which parents are responsible for adolescent re-nourishment. They play an active role in treatment and their self-efficacy to make decisions regarding their child's treatment is empowered.; Other Name: FBT
Experimental: FBT w/ Adolescent-focused Cognitive Remediation Therapy; Family Based Treatment with Adolescent-focused Cognitive Remediation Therapy (CRT): Families will receive 15 sessions of FBT over six months. The first 9 sessions of FBT will be preceded by adolescent-focused CRT.	Behavioral: Family Based Treatment; Family Based Treatment (FBT) is an evidence based treatment in which parents are responsible for adolescent re-nourishment. They play an active role in treatment and their self-efficacy to make decisions regarding their child's treatment is empowered.; Other Name: FBT; Behavioral: Cognitive Remediation Therapy; Cognitive Remediation Therapy (CRT) is an adjunctive treatment focused on increasing set-shifting ability and developing meta-cognition. CRT is a behavioral treatment that presents tasks to participants in a standardized order within each session. Each task has a number of levels. Participants stay at the same task-based level until mastered. They then move up a level on that task. participants can be at different levels on different tasks within each session. After completion of tasks, participants are asked to reflect on their thought processes in solving the tasks. Standard prompts are used to guide the discussion.; Other Name: CRT

Outcome Measures

Primary Outcome Measures :

1. Change in executive functioning [ Time Frame: Baseline, during treatment, end of treatment ]
   Investigators will use the Delis Kaplan Executive Functioning System (D-KEFS ) Trails Number-Letter Sequencing subtest, a neurocognitive behavioral task, to assess ability to set-shift (a core component of executive functioning). Investigators will compare change in scaled scores from pre, during, and post-treatment across groups. Scaled scores range from 0-19 with higher scores indicating better executive functioning.
2. Change in response inhibition [ Time Frame: Baseline, during treatment, end of treatment ]
   Investigators will use the Delis Kaplan Executive Functioning System Inhibition subtest, neurocognitive behavioral task, to assess ability to inhibit automatic responses. Investigators will compare change in scaled scores from pre, during, and post-treatment across groups. Scaled scores range from 0-19 with higher scores indicating better response inhibition.
3. Change in set-shifting [ Time Frame: Baseline, during treatment, end of treatment ]
   Also using the Delis Kaplan Executive Functioning System Inhibition task, investigators will use scores from the D-KEFS Inhibition/Switching subtest to assess ability to switch between alternating rules (a component of set shifting). Investigators will compare change in scaled scores from pre, during, and post-treatment across groups. Scaled scores range from 0-19 with higher scores indicating better set-shifting.
4. Change in shifting accuracy [ Time Frame: Baseline, during treatment, end of treatment ]
   Investigators will use the Delis Kaplan Executive Functioning System Verbal Fluency subtest, neurocognitive behavioral task, to assess accuracy in shifting categories (a component of executive functioning). Investigators will compare change in scaled scores from pre, during, and post-treatment across groups. Scaled scores range from 0-19 with higher scores indicating better shifting accuracy.
5. Change in category switching flexibility [ Time Frame: Baseline, during treatment, end of treatment ]
   Investigators will also use the Delis Kaplan Executive Functioning System Verbal Fluency subtest, category switching scores, to assess flexible switching (a component of executive functioning). Investigators will compare change in scaled scores from pre, during, and post-treatment across groups. Scaled scores range from 0-19 with higher scores indicating better switching flexibility.
6. Change in flexibility [ Time Frame: Baseline, during treatment, end of treatment ]
   Investigators will use the Delis Kaplan Executive Functioning System Sorting subtest, neurocognitive behavioral task, to assess changes in flexibility.Investigators will compare change in scaled scores from pre, during, and post-treatment across groups. Scaled scores range from 0-19 with higher scores indicating better flexibility.
7. Change in self-reported inhibition control [ Time Frame: Baseline, during treatment, end of treatment ]
   The Behavior Rating Inventory of Executive Functioning is a self and parent-report measure of executive functioning. The measure comprises 10 clinical scales, of which investigators will use the Inhibition subscale to assess self-reported inhibition control (ranged from 0-100, with higher reporting greater set-shifting ability). Investigators will compare change in T scores from pre, during, and post-treatment across groups.
8. Change in self-reported set-shifting [ Time Frame: Baseline, during treatment, end of treatment ]
   The Behavior Rating Inventory of Executive Functioning is a self and parent-report measure of executive functioning. The measure comprises 10 clinical scales, of which investigators will use the Shifting subscale to assess self-reported set-shifting. Investigators will compare change in T scores (ranged from 0-100, with higher reporting greater set-shifting ability) from pre, during, and post-treatment across groups.
9. Rate of weight gain [ Time Frame: Baseline, during treatment, end of treatment ]
   Investigators will weigh participants during treatment to compare rate of change (slope) in weight gain from pre, during, and post-treatment across groups. Larger change in weight indicates greater recovery from the eating disorder.
10. Change in eating disorder symptomology [ Time Frame: Baseline, during treatment, end of treatment ]
    Adolescents will complete the Eating Disorder Examination - Questionnaire (a 28-item self-report measure of eating disorders symptomatology), while parents will complete the Anorectic Behavior Observation Scale (a 30-item collateral report measure of eating and exercise behavior). Investigators will examine changes in these scores from baseline, during, and post-treatment. Scores range from 0-6 with higher scores suggesting more severe eating disorder symptomatology.
11. Change in behavioral flexibility (amount consumed) [ Time Frame: Baseline, during treatment, end of treatment ]
    Adolescents will complete a buffet meal during which investigators will record the amount of food they consume in grams. This task aims to assess changes in behavioral flexibility by objectively assessing food choice in individuals with an eating disorder. Investigators will examine changes from baseline, during, and at treatment completion. A larger amount of food eaten (in grams) represents greater behavioral flexibility.
12. Change in behavioral flexibility (eating disorder behaviors) [ Time Frame: Baseline, during treatment, end of treatment ]
    Adolescents will complete a buffet meal during which investigators will record eating behaviors using a novel checklist (a total score of eating disorder behaviors observed). These behaviors include staring, fidgeting, inappropriate napkin use, frequency of food tearing, frequency of dissecting food. Minimum score for this variable is 0, however, there is no maximum frequency. This task aims to assess changes in behavioral flexibility by objectively assessing eating-related behaviors in individuals with an eating disorder, with higher scores suggesting lower behavioral flexibility. Investigators will examine changes from baseline, during, and at treatment completion.

Eligibility Criteria

• Ages Eligible for Study: 12 Years and older (Child, Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria: Adolescents

1. Age 12-18
2. Currently meets Diagnostic and Statistical Manual-5 criteria for Anorexia Nervosa
3. Medically stable for outpatient treatment
4. Fluent in English
5. No co-morbid condition that would exclude participation
6. Medical clearance from primary care physician and permission to speak to Primary Care Physician about clinical issues
7. Biological parent or primary caregiver willing to engage in treatment and who lives with the adolescent

Inclusion Criteria: Parents

1. Age >18
2. Child with a diagnoses of AN
3. Parent or caregiver willing to participate
4. Fluent in English
5. No co-morbid condition that would exclude participation

Exclusion Criteria: Adolescents

1. Adolescent outside age range
2. Pregnant adolescent
3. Presence of: pervasive developmental disability, psychosis, bipolar disorder, substance abuse, autism spectrum disorder, or intellectual disability
4. Presence of: a brain disorder or injury (such as TBI) that could impact the ability to engage in treatment
5. Use of anti-psychotic medication
6. Concurrent psychosocial therapy

Exclusion Criteria: Parents

1. Presence of: pervasive developmental disability, psychosis, uncontrolled bipolar disorder, substance abuse, autism spectrum disorder, or intellectual disability.
2. Presence of: a brain disorder or injury (such as TBI) that could impact the ability to engage in treatment
3. Use of anti-psychotic medication

Contacts and Locations

Contacts

Contact: Catherine Alix Timko, PhD; 267-426-5467; timkoc@chop.edu

Contact: Amanda Makara, BS; 267-425-1321; makaraa@chop.edu

Locations

United States, Pennsylvania

Children's Hospital of Philadelphia; Recruiting

Philadelphia, Pennsylvania, United States, 19146

Contact: Catherine Alix Timko, PhD 267-426-5467 timkoc@chop.edu

Contact: Amanda Makara, BS 267-425-1321 makaraa@chop.edu

Principal Investigator: Catherine Alix Timko, PhD

Sponsors and Collaborators

Children's Hospital of Philadelphia

National Institute of Mental Health (NIMH)

Investigators

• Principal Investigator: Catherine Alix Timko, PhD; Children's Hospital of Philadelphia

More Information

Publications:

Holliday J, Tchanturia K, Landau S, Collier D, Treasure J. Is impaired set-shifting an endophenotype of anorexia nervosa? Am J Psychiatry. 2005 Dec;162(12):2269-75. doi: 10.1176/appi.ajp.162.12.2269.

Timko CA, Bhattacharya A, Fitzpatrick KK, Howe H, Rodriguez D, Mears C, Heckert K, Ubel PA, Ehrenreich-May J, Peebles R. The shifting perspectives study protocol: Cognitive remediation therapy as an adjunctive treatment to family based treatment for adolescents with anorexia nervosa. Contemp Clin Trials. 2021 Apr;103:106313. doi: 10.1016/j.cct.2021.106313. Epub 2021 Feb 1.

Kucharska K, Kulakowska D, Starzomska M, Rybakowski F, Biernacka K. The improvement in neurocognitive functioning in anorexia nervosa adolescents throughout the integrative model of psychotherapy including cognitive remediation therapy. BMC Psychiatry. 2019 Jan 9;19(1):15. doi: 10.1186/s12888-018-1984-4.

Harrison A, Stavri P, Ormond L, McEnemy F, Akyol D, Qureshi A, Al-Khairulla H. Cognitive remediation therapy for adolescent inpatients with severe and complex anorexia nervosa: A treatment trial. Eur Eat Disord Rev. 2018 May;26(3):230-240. doi: 10.1002/erv.2584. Epub 2018 Mar 15.

• Responsible Party: Children's Hospital of Philadelphia
• ClinicalTrials.gov Identifier: NCT05017831
• Other Study ID Numbers: 21-019079; 5R61MH119262-02 ( U.S. NIH Grant/Contract )
• First Posted: August 24, 2021
• Last Update Posted: January 6, 2023
• Last Verified: January 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Anorexia; Anorexia Nervosa; Signs and Symptoms, Digestive; Feeding and Eating Disorders; Mental Disorders