Shifting Perspectives: Enhancing Outcomes in Anorexia Nervosa With CRT

December 21, 2022 updated by: Children's Hospital of Philadelphia

Shifting Perspectives: Enhancing Outcomes in Adolescent Anorexia Nervosa With Cognitive Remediation Therapy (CRT)

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Actual)

177

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104
        • Children's Hospital of Philadelphia

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

12 years and older (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Factorial Assignment
  • Masking: Single

Arms and Interventions

Participant Group / 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 Names:
  • 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: 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 Names:
  • FBT
Behavioral: Cognitive Remediation Therapy
Cognitive Remediation Therapy (CRT) is an adjunctive treatment focused on increasing set-shifting ability and developing meta-cognition.
Other Names:
  • CRT
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: 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 Names:
  • FBT
Behavioral: Cognitive Remediation Therapy
Cognitive Remediation Therapy (CRT) is an adjunctive treatment focused on increasing set-shifting ability and developing meta-cognition.
Other Names:
  • CRT

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in Cognitive Flexibility - Condition 4 Trail Making Test of DKEFS
Time Frame: 6 months of treatment
The Delis Kaplan Executive Functioning System (D-KEFS) is a standardized assessment of executive functioning normed for ages 8-89 years of age. Raw scores are transformed to scaled scores: the mean is 10 with a standard deviation of 3. Higher scores indicate better performance on the test. Specific sub-tests were chosen to assess inhibitory control and cognitive flexibility. The hypothesis is that Cognitive Remediation Therapy (CRT) will increase flexibility in participants. The D-KEFS was administered at baseline (T1), after 4 weeks (T2), approximately 9 weeks (T3), approximately 17 weeks (T4), and end of treatment (T5). Trail Making Test assesses flexibility in thinking. We use Condition 4 (Number-Letter Switching) to assess flexibility.
6 months of treatment
Change in Inhibition - Condition 3 of Color-Word Interference, DKEFS
Time Frame: 6 months of treatment
The Delis Kaplan Executive Functioning System (D-KEFS) is a standardized assessment of executive functioning normed for ages 8-89 years of age. Raw scores are transformed to scaled scores: the mean is 10 with a standard deviation of 3. Higher scores indicate better performance on the test. Specific sub-tests were chosen to assess inhibitory control and cognitive flexibility. The hypothesis is that Cognitive Remediation Therapy (CRT) will increase flexibility in participants. The D-KEFS was administered at baseline (T1), after 4 weeks (T2), approximately 9 weeks (T3), approximately 17 weeks (T4), and end of treatment (T5). Inhibition refers to the ability to inhibit a well learned or salient task in order to do something different; thus, it is related to flexibility. The D-KEFS Color-Word Interference Test (Condition 3: Inhibition) to assess ability to inhibit automatic responses.
6 months of treatment
Change in Cognitive Flexibility - Condition 4 of Color Word Interference of DKEFS
Time Frame: 6 months of treatment
The Delis Kaplan Executive Functioning System (D-KEFS) is a standardized assessment of executive functioning normed for ages 8-89 years of age. Raw scores are transformed to scaled scores: the mean is 10 with a standard deviation of 3. Higher scores indicate better performance on the test. Specific sub-tests were chosen to assess inhibitory control and cognitive flexibility. The hypothesis is that Cognitive Remediation Therapy (CRT) will increase flexibility in participants. The D-KEFS was administered at baseline (T1), after 4 weeks (T2), approximately 9 weeks (T3), approximately 17 weeks (T4), and end of treatment (T5). The D-KEFS Color Word Interference (Condition 4: Inhibition/Switching) assess the ability to switch between alternating rules (a component of set shifting).
6 months of treatment
Change in Cognitive Flexibility - Verbal Fluency Switching of DKEFS
Time Frame: 6 months of treatment
The Delis Kaplan Executive Functioning System (D-KEFS) is a standardized assessment of executive functioning normed for ages 8-89 years of age. Raw scores are transformed to scaled scores: the mean is 10 with a standard deviation of 3. Higher scores indicate better performance on the test. Specific sub-tests were chosen to assess inhibitory control and cognitive flexibility. The hypothesis is that Cognitive Remediation Therapy (CRT) will increase flexibility in participants. The D-KEFS was administered at baseline (T1), after 4 weeks (T2), approximately 9 weeks (T3), approximately 17 weeks (T4), and end of treatment (T5). The D-KEFS Verbal Fluency assesses the ability to shift between concepts. The Switching Correct score is used to assess flexibility.
6 months of treatment
Change in Cognitive Flexibility - Verbal Fluency Switching of DKEFS
Time Frame: 6 months of treatment
The Delis Kaplan Executive Functioning System (D-KEFS) is a standardized assessment of executive functioning normed for ages 8-89 years of age. Raw scores are transformed to scaled scores: the mean is 10 with a standard deviation of 3. Higher scores indicate better performance on the test. Specific sub-tests were chosen to assess inhibitory control and cognitive flexibility. The hypothesis is that Cognitive Remediation Therapy (CRT) will increase flexibility in participants. The D-KEFS was administered at baseline (T1), after 4 weeks (T2), approximately 9 weeks (T3), approximately 17 weeks (T4), and end of treatment (T5). The D-KEFS Verbal Fluency assesses the ability to shift between concepts. Switching Accuracy assesses the number of times an accurate switch between categories occurs.
6 months of treatment
Change in Cognitive Flexibility - Sorting Test Description of DKEFS
Time Frame: 6 months of treatment
The Delis Kaplan Executive Functioning System (D-KEFS) is a standardized assessment of executive functioning normed for ages 8-89 years of age. Raw scores are transformed to scaled scores: the mean is 10 with a standard deviation of 3. Higher scores indicate better performance on the test. Specific sub-tests were chosen to assess inhibitory control and cognitive flexibility. The hypothesis is that Cognitive Remediation Therapy (CRT) will increase flexibility in participants. The D-KEFS was administered at baseline (T1), after 4 weeks (T2), approximately 9 weeks (T3), approximately 17 weeks (T4), and end of treatment (T5). The Sorting Test assesses flexibility in thinking and problem solving.
6 months of treatment
Change in Self-Reported Shifting - BRIEF
Time Frame: 6 months of treatment
The Behavior Rating Inventory of Executive Functioning (BRIEF) is an ecologically valid clinical tool for measuring executive functioning across several domains in youth 5 to 18 years of age; the self-report version (BRIEF-2) was administered to adolescents. It has a comparable adult self-report version (BRIEF-A) normed for ages 18-90. Both versions of the BRIEF are normed by age and sex on a T-scale (mean = 50, SD = 10), and scores are considered clinically elevated if they are 65 or higher. Both have a number of clinical scales and indices. Lower scores indicate greater strengths in each area. The hypothesis is that Cognitive Remediation Therapy (CRT) will increase flexibility in participants, thus, we expect a reduction in scores for those in the CRT conditions. The BRIEF was administered at baseline (T1), after 4 weeks (T2), approximately 9 weeks (T3), approximately 17 weeks (T4), and end of treatment (T5). The BRIEF Shift assesses behavioral flexibility.
6 months of treatment
Dose of CRT
Time Frame: 6 months of treatment
Number of sessions necessary in order to change cognitive flexibility. This is the number of sessions needed for change to occur in cognitive flexibility. It is only calculated for the participants who received CRT and who had a significant change in flexibility above what was observed in FBT.
6 months of treatment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Children's Hospital of Philadelphia

Collaborators

National Institute of Mental Health (NIMH)

Investigators

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

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

April 1, 2019

Primary Completion (Actual)

June 24, 2021

Study Completion (Actual)

June 24, 2021

Study Registration Dates

First Submitted

April 8, 2019

First Submitted That Met QC Criteria

April 24, 2019

First Posted (Actual)

April 25, 2019

Study Record Updates

Last Update Posted (Actual)

January 20, 2023

Last Update Submitted That Met QC Criteria

December 21, 2022

Last Verified

December 1, 2022

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 19-016064
  • 1R61MH119262-01 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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