4006-776-356 出国就医服务电话

免费获得国外相关药品，最快 1 个工作日回馈药物信息

出境医 / 临床实验 / Shifting Perspectives: Enhancing Outcomes in Anorexia Nervosa With CRT

Shifting Perspectives: Enhancing Outcomes in Anorexia Nervosa With CRT

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 Not Applicable

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
Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 54 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 : August 1, 2019
Estimated Primary Completion Date : June 30, 2021
Estimated Study Completion Date : June 30, 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 cognitive flexibility [ Time Frame: 7 months ]
    Delis Kaplan Executive Functioning System (D-KEFS) Trails Number-Letter Sequencing sub test

  2. Change in cognitive flexibility [ Time Frame: 7 months ]
    D-KEFS Inhibition sub test

  3. Change in cognitive flexibility [ Time Frame: 7 months ]
    D-KEFS Inhibition/Switching sub test

  4. Change in cognitive flexibility [ Time Frame: 7 months ]
    D-KEFS Correct Response Shifting sub test

  5. Change in cognitive flexibility [ Time Frame: 7 months ]
    D-KEFS Category Switching sub test

  6. Change in cognitive flexibility [ Time Frame: 7 months ]
    D-KEFS Description sub test (1 or 2)

  7. Change in cognitive flexibility [ Time Frame: 7 months ]
    Shift in sub-scale of the Behavior Rating Inventory of Executive Functioning (BRIEF)

  8. Dose of CRT [ Time Frame: 7 months ]
    Number of sessions necessary (session = subject receive dose of CRT) in order to change cognitive flexibility


Eligibility Criteria
Layout table for eligibility information
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
Layout table for location information
United States, Pennsylvania
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, United States, 19104
Sponsors and Collaborators
Children's Hospital of Philadelphia
Investigators
Layout table for investigator information
Principal Investigator: Catherine Alix Timko, PhD Children's Hospital of Philadelphia
Tracking Information
First Submitted Date  ICMJE April 8, 2019
First Posted Date  ICMJE April 25, 2019
Last Update Posted Date March 17, 2021
Actual Study Start Date  ICMJE August 1, 2019
Estimated Primary Completion Date June 30, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 24, 2019)
  • Change in cognitive flexibility [ Time Frame: 7 months ]
    Delis Kaplan Executive Functioning System (D-KEFS) Trails Number-Letter Sequencing sub test
  • Change in cognitive flexibility [ Time Frame: 7 months ]
    D-KEFS Inhibition sub test
  • Change in cognitive flexibility [ Time Frame: 7 months ]
    D-KEFS Inhibition/Switching sub test
  • Change in cognitive flexibility [ Time Frame: 7 months ]
    D-KEFS Correct Response Shifting sub test
  • Change in cognitive flexibility [ Time Frame: 7 months ]
    D-KEFS Category Switching sub test
  • Change in cognitive flexibility [ Time Frame: 7 months ]
    D-KEFS Description sub test (1 or 2)
  • Change in cognitive flexibility [ Time Frame: 7 months ]
    Shift in sub-scale of the Behavior Rating Inventory of Executive Functioning (BRIEF)
  • Dose of CRT [ Time Frame: 7 months ]
    Number of sessions necessary (session = subject receive dose of CRT) in order to change cognitive flexibility
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Shifting Perspectives: Enhancing Outcomes in Anorexia Nervosa With CRT
Official Title  ICMJE Shifting Perspectives: Enhancing Outcomes in Adolescent Anorexia Nervosa With Cognitive Remediation Therapy (CRT)
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE 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
Condition  ICMJE Anorexia Nervosa
Intervention  ICMJE
  • 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
Study Arms  ICMJE
  • Active Comparator: Family Based Treatment (FBT)
    Families will receive 15 sessions of FBT alone.
    Intervention: Behavioral: Family Based Treatment
  • 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.
    Interventions:
    • Behavioral: Cognitive Remediation Therapy
    • Behavioral: Family Based Treatment
  • 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.
    Interventions:
    • Behavioral: Cognitive Remediation Therapy
    • Behavioral: Family Based Treatment
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.
  • 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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Estimated Enrollment  ICMJE
 (submitted: April 24, 2019) 		54
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE June 30, 2021
Estimated Primary Completion Date June 30, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 12 Years and older   (Child, Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03928028
Other Study ID Numbers  ICMJE 19-016064
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Children's Hospital of Philadelphia
Study Sponsor  ICMJE Children's Hospital of Philadelphia
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Catherine Alix Timko, PhD Children's Hospital of Philadelphia
PRS Account Children's Hospital of Philadelphia
Verification Date March 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP

治疗医院

新药特效药