Shifting Perspectives: Enhancing Outcomes in Anorexia Nervosa With CRT

Not Applicable

Completed

Conditions: Anorexia Nervosa

Interventions: Behavioral: Family Based Treatment
Behavioral: Cognitive Remediation Therapy

Registration Number: NCT03928028

Lead Sponsor: Children's Hospital of Philadelphia

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 177

Inclusion Criteria

Adolescents

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

Inclusion Criteria:Parents

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

Exclusion Criteria

Adolescent

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

Exclusion Criteria: Parents

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: FACTORIAL

Arm && Interventions

Group	Intervention	Description
Family Based Treatment (FBT)	Family Based Treatment	Families will receive 15 sessions of FBT alone.
FBT w/ Parent-focused Cognitive Remediation Therapy	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.
FBT w/ Parent-focused Cognitive Remediation Therapy	Family Based Treatment	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.
FBT w/Adolescent-focused Cognitive Remediation Therapy	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.
FBT w/Adolescent-focused Cognitive Remediation Therapy	Family Based Treatment	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.

Primary Outcome Measures

Name	Time	Method
Change in Cognitive Flexibility - Verbal Fluency Switching of DKEFS	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.
Change in Cognitive Flexibility - Sorting Test Description of DKEFS	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.
Change in Cognitive Flexibility - Condition 4 of Color Word Interference of DKEFS	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).
Change in Cognitive Flexibility - Condition 4 Trail Making Test of DKEFS	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.
Change in Inhibition - Condition 3 of Color-Word Interference, DKEFS	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.
Change in Self-Reported Shifting - BRIEF	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.
Dose of CRT	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.