Shifting Perspectives: Enhancing Outcomes in Anorexia Nervosa With CRT

• ClinicalTrials.gov Identifier: NCT03928028
• Recruitment Status: Completed
• First Posted: April 25, 2019
• Last Update Posted: September 1, 2021
• 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 parents and affected adolescents in the hopes that improvements in set-shifting will, ultimately, improve outcome.

Condition or disease	Intervention/treatment	Phase
Anorexia Nervosa	Behavioral: Cognitive Remediation Therapy; Behavioral: Family Based Treatment	Phase 1

Detailed Description:

This application seeks support for a phased project. In the initial (R61) 2-year phase, the investigators will establish that Cognitive Remediation Therapy (CRT) can increase set-shifting in parents of and/or adolescents with Anorexia Nervosa (AN). The second aim is to determine the appropriate dose needed to achieve positive change in set-shifting. Attaining this milestone would trigger support for three additional years (R33) to confirm target engagement and appropriate dose. The investigators will also evaluate whether or not adding CRT to Family Based Treatment (FBT) will improve outcome compared to FBT alone. Set-shifting (a type of executive functioning often referred to as cognitive flexibility) inefficiencies are hypothesized to be an endophenotype of AN and are, therefore, heritable. Cognitive flexibility can be impacted negatively by situational factors such as malnutrition, stress, and anxiety. It is likely that both adolescents (who are malnourished) and parents (who are under stress) experience significant state-based reduction in their cognitive flexibility during AN and its treatment. While cognitive flexibility can be increased through CRT, there is a significant gap in the knowledge about how to apply CRT to the treatment of adolescent AN, specifically concerning the most appropriate target for CRT: parents or adolescents? The majority of research on CRT with adolescents with AN are pilot and feasibility studies and target set-shifting in adolescents, not parents. The investigators hypothesize that targeting parents may be more impactful for adolescent outcome. First, the investigators must determine if an increase set-shifting via CRT is possible. In the initial R61 phase, the investigators propose to recruit and randomly assign 54 families who have a child with AN to FBT, FBT with parent-focused CRT, or FBT with adolescent-focused CRT. Target engagement will be assessed via neuro-psychological assessment and self-report of cognitive and behavioral flexibility. If the investigators meet these proposed milestones in the R61 phase, they will proceed to the R33 phase. It is possible that one (N = 72 families) or both (N = 93 families) CRT conditions will be examined in the R33 phase. The investigators will confirm the findings from the R61 phase (target engagement and dose of CRT). The investigators will also examine adolescent outcome in FBT alone versus FBT+(parent or adolescent) CRT. They will gather preliminary data on putative moderators and/or mediators across both phases in order to inform results. This phased R61/R33 application is innovative in that it is the first to adapt CRT to parents only. Evidence supporting FBT+CRT to increase set-shifting in parents/adolescents will inform future efforts to leverage understanding of (heritable) neurobiology of AN in adolescents to improve outcome. Further, if CRT for parents significantly improves set-shifting, the investigators can focus efforts on how best to augment current treatments, support parents, and increase positive outcomes for the adolescent and reduce relapse. Even negative results would inform understanding of set-shifting inefficiencies as an endophenotype in AN, its measurement, and usefulness as a target in treatment.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 58 participants
• Allocation: Randomized
• Intervention Model: Factorial Assignment
• Intervention Model Description: Random assignment to one of three groups.
• Masking: Single (Outcomes Assessor)
• Masking Description: Any study team member who is assessing for outcomes will not which participant/family is in which group.
• Primary Purpose: Treatment
• Official Title: Shifting Perspectives: Enhancing Outcomes in Adolescent Anorexia Nervosa With Cognitive Remediation Therapy (CRT)
• Actual Study Start Date: April 1, 2019
• Actual Primary Completion Date: June 24, 2021
• Actual Study Completion Date: June 24, 2021

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/ Parent-focused Cognitive Remediation Therapy; Family Based Treatment with Parent-focused Cognitive Remediation Therapy (CRT): Families will receive 15 sessions of parent focused CRT followed Family Based Treatment over six months.	Behavioral: Cognitive Remediation Therapy; Cognitive Remediation Therapy (CRT) is an adjunctive treatment focused on increasing set-shifting ability and developing meta-cognition.; Other Name: 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
Experimental: FBT w/Adolescent-focused Cognitive Remediation Therapy; Family Based Treatment with Adolescent-focused Cognitive Remediation Therapy (CRT): Families will receive 15 sessions of adolescent focused CRT followed by Family Based Treatment over six months.	Behavioral: Cognitive Remediation Therapy; Cognitive Remediation Therapy (CRT) is an adjunctive treatment focused on increasing set-shifting ability and developing meta-cognition.; Other Name: 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

Outcome Measures

Primary Outcome Measures :

1. Change in executive functioning [ Time Frame: Baseline to 7 months ]
   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 T scores from pre, during, and post-treatment across groups.
2. Change in response inhibition [ Time Frame: Baseline to 7 months ]
   Investigators will use the D-KEFS Inhibition subtest, neurocognitive behavioral task, to assess ability to inhibit automatic responses. Investigators will compare change in T scores from pre, during, and post-treatment across groups.
3. Change in set shifting [ Time Frame: Baseline to 7 months ]
   Also using the D-KEFS 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 T scores from pre, during, and post-treatment across groups.
4. Change in shifting accuracy [ Time Frame: Baseline to 7 months ]
   Investigators will use the D-KEFS Verbal Fluency subtest, neurocognitive behavioral task, to assess accuracy in shifting categories (a component of executive functioning). Investigators will compare change in T scores from pre, during, and post-treatment across groups.
5. Change in category switching flexibility [ Time Frame: Baseline to 7 months ]
   Investigators will also use the D-KEFS Verbal Fluency subtest, category switching scores, to assess flexible switching (a component of executive functioning). Investigators will compare change in T scores from pre, during, and post-treatment across groups.
6. Change in flexibility [ Time Frame: Baseline to 7 months ]
   Investigators will use the D-KEFS Sorting subtest, neurocognitive behavioral task, to assess changes in flexibility. Investigators will compare change in T scores from pre, during, and post-treatment across groups.
7. Change in self-reported executive functioning [ Time Frame: Baseline to 7 months ]
   The Behavior Rating Inventory of Executive Functioning (BRIEF) is a self and parent-report measure of executive functioning. The measure comprises 10 clinical scales, of which investigators will use the subscales of Inhibition and Shifting. Investigators will compare change in T scores from pre, during, and post-treatment across groups.
8. Dose of CRT [ Time Frame: Baseline to 7 months ]
   Number of sessions necessary (session = subject receive dose of CRT) in order to change cognitive flexibility

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 live with the adolescent

Inclusion Criteria:Parents

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

Exclusion Criteria: Adolescent

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

Exclusion Criteria: Parents

1. Presence of: pervasive developmental disability, psychosis, 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

Locations

United States, Pennsylvania

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States, 19104

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

  Study Documents (Full-Text)

Documents provided by Children's Hospital of Philadelphia:

Informed Consent Form  [PDF] March 26, 2020

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.

Lang K, Stahl D, Espie J, Treasure J, Tchanturia K. Set shifting in children and adolescents with anorexia nervosa: an exploratory systematic review and meta-analysis. Int J Eat Disord. 2014 May;47(4):394-9. doi: 10.1002/eat.22235. Epub 2013 Dec 18. Review.

Roberts ME, Tchanturia K, Stahl D, Southgate L, Treasure J. A systematic review and meta-analysis of set-shifting ability in eating disorders. Psychol Med. 2007 Aug;37(8):1075-84. Epub 2007 Jan 30. Review.

Roberts ME, Tchanturia K, Treasure JL. Exploring the neurocognitive signature of poor set-shifting in anorexia and bulimia nervosa. J Psychiatr Res. 2010 Oct;44(14):964-70. doi: 10.1016/j.jpsychires.2010.03.001. Epub 2010 Apr 15.

Lang K, Treasure J, Tchanturia K. Is inefficient cognitive processing in anorexia nervosa a familial trait? A neuropsychological pilot study of mothers of offspring with a diagnosis of anorexia nervosa. World J Biol Psychiatry. 2016 Jun;17(4):258-65. doi: 10.3109/15622975.2015.1112035. Epub 2015 Dec 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.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: Children's Hospital of Philadelphia
• ClinicalTrials.gov Identifier: NCT03928028
• Other Study ID Numbers: 19-016064; 1R61MH119262-01 ( U.S. NIH Grant/Contract )
• First Posted: April 25, 2019
• Last Update Posted: September 1, 2021
• Last Verified: August 2021

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