<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT04479683</url>
  </required_header>
  <id_info>
    <org_study_id>APHP190069</org_study_id>
    <nct_id>NCT04479683</nct_id>
  </id_info>
  <brief_title>COmparison Between Continued Inpatient Treatment Versus Day Patient Treatment in Early Onset Anorexia Nervosa</brief_title>
  <acronym>COTIDEA</acronym>
  <official_title>&quot;COTIDEA COmparison Between Continued Inpatient Treatment Versus Day Patient Treatment (Partial Hospitalization) After Short Inpatient Care in Early Onset Anorexia Nervosa: a Non-inferiority Trial A Non-inferiority Study&quot;</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Assistance Publique - Hôpitaux de Paris</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Assistance Publique - Hôpitaux de Paris</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      &quot;In so-called &quot;&quot;early onset&quot;&quot; anorexia nervosa (AN), a rare and severe form affecting 8-13&#xD;
      year olds, experts recommend that, as soon as possible, treatment should take place on an&#xD;
      outpatient basis, at an age when separation from the usual environment would be particularly&#xD;
      unpleasant and deleterious. However, in severe AN, full-time hospitalisation (FTH) is still&#xD;
      indicated when somatic and psychiatric instability criteria are met. Thus, the severity and&#xD;
      rapidity of undernutrition in children aged 8-13 years suffering from AN (linked on the one&#xD;
      hand to the frequency of total aphagia with refusal to drink and on the other hand to the&#xD;
      lack of early detection of the disorder, frequently requires emergency FTH, contrary to&#xD;
      expert recommendations. This FTH, which lasts on average 3 months in our specialized unit,&#xD;
      has certain disadvantages: poor acceptability by the patient and/or his family, increased&#xD;
      anxiety symptoms on entry and exit, school dropout, social isolation, coercive experience. In&#xD;
      addition, the rate of premature FTH exits - before weight targets are reached - and the&#xD;
      frequency of relapses after FTH remain high, making FTH unsatisfactory in terms of&#xD;
      cost-effectiveness. Some families refuse FTH, which is classically long, exposing themselves&#xD;
      to the risk of complications that can occur if the disorder is inadequately treated: somatic,&#xD;
      acute and chronic complications; risk of progression to another eating disorder.&#xD;
&#xD;
      In recent years, day hospitalization (DH) care has been developed for adolescents aged 11 to&#xD;
      18 years and adults (Madden, 2015). The few studies available are in favour of comparable&#xD;
      efficacy, better acceptability and lower cost in the management of moderate AN compared to&#xD;
      prolonged FTH, but also better social adaptation.In children aged 8 to 13 years with AN,&#xD;
      whose somatic condition requires continuous monitoring in a hospital setting (the usual&#xD;
      indication for FTH), a DH cannot reasonably be proposed immediately given the severity of the&#xD;
      situation. Our hypothesis is that it would however be possible, in these children, to shorten&#xD;
      the duration of FTH and to continue DH treatment once the critical period has passed at the&#xD;
      somatic level, with comparable efficacy, best acceptability, best progress in terms of school&#xD;
      and social integration, and lower cost.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The objective of the study is to demonstrate the non-inferiority of DH management after a&#xD;
      short full-time hospitalisation compared to a prolonged full-time hospitalisation aiming at a&#xD;
      healthy weight on the evolution of BMI at 1 year in children aged 8 to 13 years suffering&#xD;
      from anorexia nervosa, with severe undernutrition.&#xD;
&#xD;
      The minimum healthy weight is defined by a weight corresponding to the BMI corridor prior to&#xD;
      the diagnosis of anorexia nervosa, +/- 1 corridor).&#xD;
&#xD;
      Randomized controlled trial, open-label, single-centre.&#xD;
&#xD;
      Patients will be randomized into one of the two arms of the trial:&#xD;
&#xD;
        -  Group 1 (control group): continuation of full-time hospitalisation until reaching the&#xD;
           minimum healthy weight, defined as the weight corresponding to the return to the&#xD;
           previous BMI corridor (previous BMI +/- 1 BMI corridor, e.g. change from 25th to 10th&#xD;
           percentile).&#xD;
&#xD;
        -  Group 2 (experimental group): Exit from FTH (full-time hospitalisation ) and relay to DH&#xD;
           (day hospitalization ) one day per week until the minimum healthy weight. This treatment&#xD;
           combines a one-day medical evaluation by a senior psychiatrist, family sessions (parents&#xD;
           group and multi-family therapy session), a therapeutic education group, a cognitive&#xD;
           remediation group and a dietary follow-up with therapeutic meals.&#xD;
&#xD;
      Statistical analysis of the data will be carried out with the intention to treat. The BMI at&#xD;
      1 year between groups, as well as its bilateral 95% confidence interval (equivalent to a&#xD;
      one-sided 97.5% confidence interval), will be estimated and compared with the predefined&#xD;
      margin of non-inferiority (1 BMI point).&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">May 10, 2021</start_date>
  <completion_date type="Anticipated">May 2025</completion_date>
  <primary_completion_date type="Anticipated">May 2025</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>BMI BMI</measure>
    <time_frame>one year</time_frame>
    <description>body mass index (BMI) at 1 year after admission into FTH</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>global clinical state</measure>
    <time_frame>3 months, 6 months and 1 year after admission into FTH</time_frame>
    <description>Clinical global impression scale (CGI).Two &quot;sub-scores&quot;: CGI-gravity and CGI-improvement.&#xD;
CGI-gravity measures the severity of a subject's current clinical condition (from 1 &quot;normal, not at all sick&quot; to 7 &quot;among the sickest patients&quot;). The improvement measures the perceived improvement in clinical status between assessments (rated from 1 &quot;Very Much Improved&quot; to 7 &quot;Very Much Worsened&quot;).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Weight</measure>
    <time_frame>at normalization of physiological parameters,3 months, 6 months and 1 year after admission into FTH</time_frame>
    <description>Evaluate a healthy weight of a FTH intervention then DH versus conventional treatment</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Height</measure>
    <time_frame>at normalization of physiological parameters,3 months, 6 months and 1 year after admission into FTH</time_frame>
    <description>Evaluate a height of a FTH intervention then DH versus conventional treatment</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of weight recurrences</measure>
    <time_frame>12 months</time_frame>
    <description>relapse risk assessment</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>number of rehospitalization days</measure>
    <time_frame>12 months</time_frame>
    <description>relapse risk assessment</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Quality of life of patients and parents</measure>
    <time_frame>6 months and 12 months</time_frame>
    <description>Score on the satisfaction questionnaire (CSQ 8 and SF12)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cost FTH then DH versus conventional treatment</measure>
    <time_frame>12 months</time_frame>
    <description>Evaluate the efficiency of the FTH then DH versus FTH alone through a cost-utility analysis, and perform a cost-effectiveness analysis.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>anxiety and depression</measure>
    <time_frame>at normalization of physiological parameters,12 months</time_frame>
    <description>The evolution of anxiety by Children Depression Inventory scale and State-Trait Anxiety Inventory</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Self-esteem</measure>
    <time_frame>at normalization of physiological parameters,12 months</time_frame>
    <description>The evolution of self-esteem by Rosenberg self-esteem scale</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">88</enrollment>
  <condition>Early Onset Anorexia Nervosa</condition>
  <arm_group>
    <arm_group_label>standard care</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>continuation of full-time hospitalization until the minimum healthy weight is reached, defined as the weight corresponding to the return to the previous BMI corridor (previous BMI +/- 1 BMI corridor, e.g. change from 25th to 10th percentile). This management combines bi-weekly medical follow-up by a senior psychiatrist, weekly family work, weekly therapeutic education group, weekly cognitive remediation group and bi-weekly dietary follow-up with therapeutic meals.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>FTH (full-time hospitalisation) then day hospitalization)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>FTH output and DH relay one day a week until the minimum healthy weight. This treatment combines over one day a medical evaluation by a senior psychiatrist, family work (parents group and multi-family therapy session), a therapeutic education group, a cognitive remediation group and a dietary follow-up with therapeutic meals.&#xD;
During this phase, all children are evaluated once a week on a somatic level.</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>FTH then DH support</intervention_name>
    <description>FTH output and DH relay one day a week until the minimum healthy weight. This treatment combines over one day a medical evaluation by a senior psychiatrist, family work (parents group and multi-family therapy session), a therapeutic education group, a cognitive remediation group and a dietary follow-up with therapeutic meals.&#xD;
During this phase, all children are evaluated once a week on a somatic level.</description>
    <arm_group_label>FTH (full-time hospitalisation) then day hospitalization)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>standard care</intervention_name>
    <description>continuation of full-time hospitalization until the minimum healthy weight is reached, defined as the weight corresponding to the return to the previous BMI corridor (previous BMI +/- 1 BMI corridor, e.g. change from 25th to 10th percentile). This management combines bi-weekly medical follow-up by a senior psychiatrist, weekly family work, weekly therapeutic education group, weekly cognitive remediation group and bi-weekly dietary follow-up with therapeutic meals.</description>
    <arm_group_label>standard care</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Anorexia Nervosa according to diagnostic mental disorders(DSM 5) criteria;&#xD;
&#xD;
          -  Age at diagnosis 8 to 13 years inclusive;&#xD;
&#xD;
          -  Indication for full-time hospitalisation according to supreme health authority (HAS&#xD;
             2010) criteria, see appendix;&#xD;
&#xD;
          -  First hospitalization in the Eating Disorders (ED) unit of the Child and Adolescent&#xD;
             Psychiatry Department at Robert Debré Hospital.&#xD;
&#xD;
          -  Informed consent of the holder(s) of parental authority&#xD;
&#xD;
          -  Patient affiliated to a social security&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Other early onset eating disorders (ARFID to DSM 5 criteria) ;&#xD;
&#xD;
          -  Underlying unbalanced somatic disease (especially gastroenterological);&#xD;
&#xD;
          -  Psychiatric indication for continued hospitalisation (in particular significant&#xD;
             suicidal risk according to the psychiatric criteria for full-time hospitalisation for&#xD;
             anorexia nervosa of the HAS, 2010, cf. appendix)&#xD;
&#xD;
          -  Environmental indication for continued full-time hospitalization according to the HAS&#xD;
             environmental criteria for full-time hospitalization for anorexia nervosa, 2010, cf.&#xD;
             appendix) ;&#xD;
&#xD;
          -  History of full-time hospitalisation in our ED unit.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>8 Years</minimum_age>
    <maximum_age>13 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Stordeur Coline, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>APHP</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Stordeur Coline, MD</last_name>
    <phone>+33140032261</phone>
    <email>coline.stordeur@aphp.fr</email>
  </overall_contact>
  <location>
    <facility>
      <name>Hôpital Robert Debré</name>
      <address>
        <city>Paris</city>
        <zip>75019</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Stordeur Coline, PHD</last_name>
      <email>coline.stordeur@aphp.fr</email>
    </contact>
  </location>
  <location_countries>
    <country>France</country>
  </location_countries>
  <verification_date>August 2022</verification_date>
  <study_first_submitted>July 8, 2020</study_first_submitted>
  <study_first_submitted_qc>July 16, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 21, 2020</study_first_posted>
  <last_update_submitted>August 2, 2022</last_update_submitted>
  <last_update_submitted_qc>August 2, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">August 3, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Anorexia</mesh_term>
    <mesh_term>Anorexia Nervosa</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT04479683
org study id: APHP190069
nct id: NCT04479683
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
"In so-called ""early onset"" anorexia nervosa (AN), a rare and severe form affecting 8-13
      year olds, experts recommend that, as soon as possible, treatment should take place on an
      outpatient basis, at an age when separation from the usual environment would be particularly
      unpleasant and deleterious. However, in severe AN, full-time hospitalisation (FTH) is still
      indicated when somatic and psychiatric instability criteria are met. Thus, the severity and
      rapidity of undernutrition in children aged 8-13 years suffering from AN (linked on the one
      hand to the frequency of total aphagia with refusal to drink and on the other hand to the
      lack of early detection of the disorder, frequently requires emergency FTH, contrary to
      expert recommendations. This FTH, which lasts on average 3 months in our specialized unit,
      has certain disadvantages: poor acceptability by the patient and/or his family, increased
      anxiety symptoms on entry and exit, school dropout, social isolation, coercive experience. In
      addition, the rate of premature FTH exits - before weight targets are reached - and the
      frequency of relapses after FTH remain high, making FTH unsatisfactory in terms of
      cost-effectiveness. Some families refuse FTH, which is classically long, exposing themselves
      to the risk of complications that can occur if the disorder is inadequately treated: somatic,
      acute and chronic complications; risk of progression to another eating disorder.

      In recent years, day hospitalization (DH) care has been developed for adolescents aged 11 to
      18 years and adults (Madden, 2015). The few studies available are in favour of comparable
      efficacy, better acceptability and lower cost in the management of moderate AN compared to
      prolonged FTH, but also better social adaptation.In children aged 8 to 13 years with AN,
      whose somatic condition requires continuous monitoring in a hospital setting (the usual
      indication for FTH), a DH cannot reasonably be proposed immediately given the severity of the
      situation. Our hypothesis is that it would however be possible, in these children, to shorten
      the duration of FTH and to continue DH treatment once the critical period has passed at the
      somatic level, with comparable efficacy, best acceptability, best progress in terms of school
      and social integration, and lower cost.
The objective of the study is to demonstrate the non-inferiority of DH management after a
      short full-time hospitalisation compared to a prolonged full-time hospitalisation aiming at a
      healthy weight on the evolution of BMI at 1 year in children aged 8 to 13 years suffering
      from anorexia nervosa, with severe undernutrition.

      The minimum healthy weight is defined by a weight corresponding to the BMI corridor prior to
      the diagnosis of anorexia nervosa, +/- 1 corridor).

      Randomized controlled trial, open-label, single-centre.

      Patients will be randomized into one of the two arms of the trial:

        -  Group 1 (control group): continuation of full-time hospitalisation until reaching the
           minimum healthy weight, defined as the weight corresponding to the return to the
           previous BMI corridor (previous BMI +/- 1 BMI corridor, e.g. change from 25th to 10th
           percentile).

        -  Group 2 (experimental group): Exit from FTH (full-time hospitalisation ) and relay to DH
           (day hospitalization ) one day per week until the minimum healthy weight. This treatment
           combines a one-day medical evaluation by a senior psychiatrist, family sessions (parents
           group and multi-family therapy session), a therapeutic education group, a cognitive
           remediation group and a dietary follow-up with therapeutic meals.

      Statistical analysis of the data will be carried out with the intention to treat. The BMI at
      1 year between groups, as well as its bilateral 95% confidence interval (equivalent to a
      one-sided 97.5% confidence interval), will be estimated and compared with the predefined
      margin of non-inferiority (1 BMI point).
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: BMI BMI
time frame: one year
description: body mass index (BMI) at 1 year after admission into FTH
measure: global clinical state
time frame: 3 months, 6 months and 1 year after admission into FTH
description: Clinical global impression scale (CGI).Two "sub-scores": CGI-gravity and CGI-improvement.
CGI-gravity measures the severity of a subject's current clinical condition (from 1 "normal, not at all sick" to 7 "among the sickest patients"). The improvement measures the perceived improvement in clinical status between assessments (rated from 1 "Very Much Improved" to 7 "Very Much Worsened").
measure: Weight
time frame: at normalization of physiological parameters,3 months, 6 months and 1 year after admission into FTH
description: Evaluate a healthy weight of a FTH intervention then DH versus conventional treatment
measure: Height
time frame: at normalization of physiological parameters,3 months, 6 months and 1 year after admission into FTH
description: Evaluate a height of a FTH intervention then DH versus conventional treatment
measure: Number of weight recurrences
time frame: 12 months
description: relapse risk assessment
measure: number of rehospitalization days
time frame: 12 months
description: relapse risk assessment
measure: Quality of life of patients and parents
time frame: 6 months and 12 months
description: Score on the satisfaction questionnaire (CSQ 8 and SF12)
measure: Cost FTH then DH versus conventional treatment
time frame: 12 months
description: Evaluate the efficiency of the FTH then DH versus FTH alone through a cost-utility analysis, and perform a cost-effectiveness analysis.
measure: anxiety and depression
time frame: at normalization of physiological parameters,12 months
description: The evolution of anxiety by Children Depression Inventory scale and State-Trait Anxiety Inventory
measure: Self-esteem
time frame: at normalization of physiological parameters,12 months
description: The evolution of self-esteem by Rosenberg self-esteem scale
arm group label: standard care
arm group type: Other
description: continuation of full-time hospitalization until the minimum healthy weight is reached, defined as the weight corresponding to the return to the previous BMI corridor (previous BMI +/- 1 BMI corridor, e.g. change from 25th to 10th percentile). This management combines bi-weekly medical follow-up by a senior psychiatrist, weekly family work, weekly therapeutic education group, weekly cognitive remediation group and bi-weekly dietary follow-up with therapeutic meals.
arm group label: FTH (full-time hospitalisation) then day hospitalization)
arm group type: Experimental
description: FTH output and DH relay one day a week until the minimum healthy weight. This treatment combines over one day a medical evaluation by a senior psychiatrist, family work (parents group and multi-family therapy session), a therapeutic education group, a cognitive remediation group and a dietary follow-up with therapeutic meals.
During this phase, all children are evaluated once a week on a somatic level.
intervention type: Other
intervention name: FTH then DH support
description: FTH output and DH relay one day a week until the minimum healthy weight. This treatment combines over one day a medical evaluation by a senior psychiatrist, family work (parents group and multi-family therapy session), a therapeutic education group, a cognitive remediation group and a dietary follow-up with therapeutic meals.
During this phase, all children are evaluated once a week on a somatic level.
arm group label: FTH (full-time hospitalisation) then day hospitalization)
intervention type: Other
intervention name: standard care
description: continuation of full-time hospitalization until the minimum healthy weight is reached, defined as the weight corresponding to the return to the previous BMI corridor (previous BMI +/- 1 BMI corridor, e.g. change from 25th to 10th percentile). This management combines bi-weekly medical follow-up by a senior psychiatrist, weekly family work, weekly therapeutic education group, weekly cognitive remediation group and bi-weekly dietary follow-up with therapeutic meals.
arm group label: standard care
criteria: 
gender: All
minimum age: 8 Years
maximum age: 13 Years
healthy volunteers: No
last name: Stordeur Coline, MD
role: Principal Investigator
affiliation: APHP
last name: Stordeur Coline, MD
phone: +33140032261
email: coline.stordeur@aphp.fr
facility: 
status: Recruiting
contact: 
country: France
responsible party type: Sponsor
mesh term: Anorexia
mesh term: Anorexia Nervosa
sharing ipd: No