Shifting Perspectives: Enhancing Outcomes in Anorexia Nervosa With CRT

NCT ID: NCT03928028

Last Updated: 2023-01-20

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 177 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-04-01
• Study Completion Date: 2021-06-24

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.

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.

Conditions

Anorexia Nervosa

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: FACTORIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

Family Based Treatment (FBT)

Families will receive 15 sessions of FBT alone.

Group Type: ACTIVE_COMPARATOR

Family Based Treatment

Intervention Type: BEHAVIORAL

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.

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.

Group Type: EXPERIMENTAL

Cognitive Remediation Therapy

Intervention Type: BEHAVIORAL

Cognitive Remediation Therapy (CRT) is an adjunctive treatment focused on increasing set-shifting ability and developing meta-cognition.

Family Based Treatment

Intervention Type: BEHAVIORAL

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.

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.

Group Type: EXPERIMENTAL

Cognitive Remediation Therapy

Intervention Type: BEHAVIORAL

Cognitive Remediation Therapy (CRT) is an adjunctive treatment focused on increasing set-shifting ability and developing meta-cognition.

Family Based Treatment

Intervention Type: BEHAVIORAL

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.

Interventions

Cognitive Remediation Therapy

Cognitive Remediation Therapy (CRT) is an adjunctive treatment focused on increasing set-shifting ability and developing meta-cognition.

Intervention Type: 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.

Intervention Type: BEHAVIORAL

Other Intervention Names

CRT; FBT

Eligibility Criteria

Inclusion Criteria

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

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

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

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

• Minimum Eligible Age: 12 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institute of Mental Health (NIMH)

NIH

Sponsor Role: collaborator

Children's Hospital of Philadelphia

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Catherine Alix Timko, PhD

Role: PRINCIPAL_INVESTIGATOR

Children's Hospital of Philadelphia

Locations

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States

Countries

United States

References

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.

Reference Type: BACKGROUND

PMID: 16330590 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 24347025 (View on PubMed)

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. doi: 10.1017/S0033291707009877. Epub 2007 Jan 30.

Reference Type: BACKGROUND

PMID: 17261218 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 20398910 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 26563611 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 30626367 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 29542258 (View on PubMed)

Susanin A, Cooper M, Makara A, Kuschner ES, Timko CA. Autistic characteristics in youth with anorexia nervosa before and after treatment. Eur Eat Disord Rev. 2022 Sep;30(5):664-670. doi: 10.1002/erv.2937. Epub 2022 Jul 3.

Reference Type: DERIVED

PMID: 35780511 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 33539993 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

1R61MH119262-01

Identifier Type: NIH

Identifier Source: secondary_id

View Link

19-016064

Identifier Type: -

Identifier Source: org_study_id