<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/NCT02237300</url>
  </required_header>
  <id_info>
    <org_study_id>PSI2011-28801</org_study_id>
    <secondary_id>PSI2011-28801</secondary_id>
    <nct_id>NCT02237300</nct_id>
  </id_info>
  <brief_title>Virtual Reality Based Cue-exposure Treatment for Bulimia Nervosa</brief_title>
  <official_title>Tratamiento de la Bulimia Nerviosa Mediante exposición a señales Con Realidad Virtual</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Barcelona</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Hospital Universitari de Bellvitge</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Consorci Sanitari de l'Anoia</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Centro ABB</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Hospital Universitari Joan XXIII de Tarragona.</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Istituto Auxologico Italiano</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Barcelona</source>
  <oversight_info>
    <has_dmc>Yes</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>
      Introduction: The purpose of this research is to develop a new component for&#xD;
      cognitive-behavioral treatment (CBT), empirically validated, for binge eating behavior in&#xD;
      patients with bulimia nervosa (BN) and binge eating disorder (BED), by means of cue-exposure&#xD;
      therapy (CET) with virtual reality. While CBT is an effective treatment for these eating&#xD;
      disorders, an important percentage of patients do not improve despite treatment. It is&#xD;
      necessary to explore how to enhance the effectivity of usual treatments with the&#xD;
      incorporation of new technologies and procedures. The innovation of this investigation is&#xD;
      based on the use of VR for cue-exposure therapy, which has been found effective with patients&#xD;
      resistant to conventional treatments (CBT and pharmacological intervention), and seeks to&#xD;
      enhance this efficacy by increasing possibilities of generalization and providing more useful&#xD;
      tools to clinicians, diminishing the logistic complications of the exposure to real cues&#xD;
      (food).&#xD;
&#xD;
      Participants: 60 patients with a diagnosis of BN or BED according the DSM-5 who had been&#xD;
      proposed for participation in the study by their referral mental health's professional after&#xD;
      conducting unsuccessfully a first level treatment (CBT structured intervention) at the&#xD;
      clinical sites involved will participate in the study.&#xD;
&#xD;
      Procedure: Participants with active episodes of binge eating (and purging, in the case of BN)&#xD;
      during the last 2 weeks of the structured intervention of CBT will be provided with detailed&#xD;
      information about the study. All patients who agree to participate in the study and who sign&#xD;
      the informed consent form will be randomly assigned to one of the two second-level treatment&#xD;
      conditions: virtual reality based cue-exposure therapy (VR-CET) or additional&#xD;
      cognitive-behavioral treatment (A-CBT). Both second-level treatment conditions consist of six&#xD;
      60-minute sessions that are held two times per week over a period of three weeks.&#xD;
&#xD;
      In an interview setting, all of the participants will be administered several questionnaires&#xD;
      (BN, DT and BD subscales of EDI-3, FCQ-T/S, and STAI-Y) and participants assigned to the&#xD;
      VR-CET will also be exposed to various types of virtual foods in different virtual&#xD;
      environments (kitchen, dining-room, bedroom, and café) where they will be asked about their&#xD;
      food cravings and anxiety experienced in each situation to develop a proper exposure&#xD;
      hierarchy according to the specific characteristics and needs of each patient.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Sample Sixty patients who have been diagnosed with BN or BED according to the Diagnostic and&#xD;
      Statistical Manual of Mental Disorders Fifth Edition (DSM-5) and who have been found to be&#xD;
      resistant to an initial structured program of CBT (Fairburn, Marcus, &amp; Wilson, 1993) will&#xD;
      participate in the study. Participants will be recruited from collaborating hospitals and&#xD;
      health centers including Hospital de Bellvitge (Barcelona, Spain), Adult Mental Health Center&#xD;
      of the Consorcio Sanitario de la Anoia (Igualada, Spain), Hospital Universitari Joan XXIII&#xD;
      (Tarragona, Spain), Centro ABB (Tarragona, Spain) and the Instituto Auxologico Italiano&#xD;
      (Milano, Italy). Suicidal ideation and diagnoses of other severe mental disorders (substance&#xD;
      use disorders, bipolar disorder, psychosis) are exclusion criteria. Patients with active&#xD;
      episodes of binge eating (and purging, in case of BN) during the last two weeks of the&#xD;
      structured program of CBT will be considered for participation in the study. All prospective&#xD;
      participants will be comprehensively informed about the characteristics of the study and will&#xD;
      be required to sign an informed consent form. Authorization of the research ethics committees&#xD;
      of the applicant organization (University of Barcelona) and the collaborating institutions&#xD;
      will be required.&#xD;
&#xD;
      Patients who agree to participate in the study will be randomly assigned to one of two&#xD;
      second-level treatment conditions: the VR-CET group will receive cue-exposure sessions using&#xD;
      VR environments (six 60-minute (maximum) sessions over the course of three weeks; two per&#xD;
      week) and the A-CBT group will receive six additional sessions of the usual cognitive&#xD;
      behavioral treatment. Consistent with the American Psychological Association and the CONSORT&#xD;
      guideline recommendations regarding sample size in this type of research, 30 patients will be&#xD;
      included in each group. If necessary, dropout cases will be replaced.&#xD;
&#xD;
      Procedure At the end of the first level of treatment with the structured program of CBT, all&#xD;
      patients will be assessed relative to their status and will complete several questionnaires&#xD;
      (BN, DT and BD subscales of EDI-3, FCQ-T/S, and STAI-Y) (pre-randomization assessment).&#xD;
&#xD;
      Those with active behavioral symptoms who agree to participate in the intervention study and&#xD;
      who have signed the informed consent form will be randomly assigned to one of the two&#xD;
      second-level treatment conditions: VR-CET or A-CBT sessions. Also, participants assigned to&#xD;
      the VR-CET condition will be assessed through a validated VR-based cue exposure software&#xD;
      (Gutiérrez-Maldonado, Pla-Sanjuanelo et al., 2016) in order to construct the exposure&#xD;
      hierarchy of 3D interactive (environment and food) situations, used in the VR-CET sessions.&#xD;
      For that, participants assigned to the VR-CET condition:&#xD;
&#xD;
        1. Will be exposed to 30 graphic representations of different foods. The level of craving&#xD;
           elicited by each food will be assessed by means of a visual analog scale (VAS) that&#xD;
           ranges from 0 (not at all) to 100 (extreme).&#xD;
&#xD;
        2. These participants will also be exposed to four graphic representations of different&#xD;
           environments (kitchen, dining room, bedroom, and café). The level of craving elicited by&#xD;
           each environment will be assessed by means of a VAS that ranges from 0 (not at all) to&#xD;
           100 (extreme).&#xD;
&#xD;
        3. They will be individually exposed to the ten different virtual foods assessed as&#xD;
           eliciting the highest levels of craving in each of the four virtual environments&#xD;
           (kitchen, dining room, bedroom, and café) for a total of 40 virtual situations from&#xD;
           lowest to highest craving scores as previously registered in phases 1 and 2. Once in the&#xD;
           virtual situation, the participant will be asked to sit at a virtual table where the&#xD;
           food is placed. Once the participant sits, the time is measured. During the first 20&#xD;
           seconds, the patient can handle the virtual food by means of the laptop's mouse but&#xD;
           cannot eat the food. When time runs out, the levels of craving and anxiety will be&#xD;
           assessed by means of visual analog scales that range from 0 (not at all) to 100&#xD;
           (extreme). Virtual environments will be displayed by means of a 3D laptop with specific&#xD;
           software that is capable of creating a stereoscopic effect that is duly processed by&#xD;
           polarized glasses. Headphones will also be used. This assessment will be conducted in a&#xD;
           quiet darkened room to increase the participant's immersion in the virtual scenarios.&#xD;
           The therapist will remain behind the patient during the assessment so as not to&#xD;
           interfere with the task but to be available in the event a participant requires&#xD;
           assistance.&#xD;
&#xD;
        4. Anxiety scores obtained from each of the 40 situations will be used to develop the&#xD;
           exposure hierarchy that will be used in the VR-CET sessions.&#xD;
&#xD;
      Virtual reality based cue-exposure therapy (VR-CET) sessions: There will be six 60-minute&#xD;
      (maximum) exposure sessions (two sessions per week for three weeks). Participants (n=30) will&#xD;
      be exposed to different VR environments related to binge behaviors, according to the&#xD;
      previously constructed hierarchy. During exposure, patients will face high risk situations to&#xD;
      diminish or extinguish the conditioned response of anxiety when exposed to food related cues.&#xD;
      In each session, the patient will be exposed to the corresponding steps of the hierarchy.&#xD;
&#xD;
      Additional cognitive-behavioral treatment (A-CBT) sessions: Participants (n=30) in this&#xD;
      condition will receive six CBT booster sessions (twice weekly) over the course of three weeks&#xD;
      to improve the output of treatment. CBT sessions are based on the approach described by&#xD;
      Eldredge and colleagues (Eldredge et al., 1997). In this treatment, patients are trained to&#xD;
      self-monitor their food patterns and to identify and manage thoughts, emotions, and&#xD;
      environmental factors related to disrupted eating behaviors.&#xD;
&#xD;
      VR based cue-exposure booster sessions The cue-exposure procedure used in this study is an&#xD;
      adaptation of the cue-exposure treatment for BN proposed by Martinez-Mallen et al. (2007).&#xD;
      Exposure sessions will be conducted individually in a quiet, darkened room. In each session,&#xD;
      the participant will sit in front of a 3D laptop with software that is capable of creating a&#xD;
      stereoscopic effect that is duly processed by polarized glasses. Headphones with active noise&#xD;
      cancellation will also be used to expose the participant to the auditory stimuli in the&#xD;
      virtual environments and, at the same time, to isolate the patient from external noises.&#xD;
      Participants can interact within the virtual environments in real time. They can move around&#xD;
      the scenarios, sit at a table, and they can handle foods displayed using the keyboard and the&#xD;
      laptop's mouse.&#xD;
&#xD;
      During the first minutes of the session, patients will be reminded of the purpose of the&#xD;
      exposure, that is, to place them in contact with food despite the high levels of anxiety they&#xD;
      experience. Doubts and questions raised by the participants will be attended to at this time.&#xD;
      The participants will be exposed to the corresponding virtual environments and foods based on&#xD;
      the previously established hierarchy. Along the VR-CET sessions, craving and anxiety levels&#xD;
      were assessed periodically. Exposure will terminate when subjective anxiety has decreased a&#xD;
      40% in relation to the level registered at the initiation of the exposure session or after 60&#xD;
      minutes. Once the anxiety level has decreased significantly, the patient will be exposed to&#xD;
      the next level in the hierarchy. In the event the session terminates before the anxiety level&#xD;
      has been sufficiently reduced in the virtual situations, the patients will be exposed to the&#xD;
      same situation in the following session. Subjective craving and anxiety will be recorded&#xD;
      using visual analogic scales (VAS) that range from 0 (not at all) to 100 (extreme) at the&#xD;
      beginning, every minute, and at the end of the virtual scenario exposures. During exposure,&#xD;
      the therapist will remain behind the patient and will only intervene if instruction is needed&#xD;
      or if the patient needs assistance.&#xD;
&#xD;
      Assessment During each VR-CET session, subjective craving and anxiety will be assessed using&#xD;
      VAS (range from 0 to 100) and will be recorded at the beginning, every minute, and at the end&#xD;
      of the exposure.&#xD;
&#xD;
      The following questionnaires will be administered to the participants of the two groups&#xD;
      before initiating treatment (pre-randomization phase), at the end of the second level-level&#xD;
      treatment conditions, and at the six-month follow-up: STAI-Y (State-Trait Anxiety&#xD;
      Inventory-Form Y), BN, DT and BD subscales of EDI-3 (Eating Disorders Inventory-3) and&#xD;
      FCQ-T/S (Food Craving Questionnaire-Trait/State).&#xD;
&#xD;
      Finally, outcome assessment for core behavioural features included frequency (i.e., number)&#xD;
      of binge eating episodes and purging during the two weeks prior to beginning the second-level&#xD;
      treatment conditions, during the two weeks after the end of the intervention, and during two&#xD;
      weeks after six-month follow-up.&#xD;
&#xD;
      Data analyses Mixed between-within subject analysis of variance will be conducted.&#xD;
      Between-subject variable refers to both conditions, the VR-CET versus A-CBT. The&#xD;
      within-subject variable refers to the assessment time: prior to beginning the second-level&#xD;
      treatment conditions (both VR-CET and A-CBT conditions), at the end of the treatment, and at&#xD;
      the six-month follow-up. Thus, comparisons between results obtained by both groups before&#xD;
      treatment, after treatment and at follow-up for each of the assessed measures will be&#xD;
      conducted. Using a similar analysis, anxiety measures registered during each exposure session&#xD;
      will also be compared.&#xD;
&#xD;
      A significant interaction between condition (VR-CET vs. A-CBT) and time is expected in the&#xD;
      first block of analyses. This would indicate that the results of the questionnaires as well&#xD;
      as the number of binges and purges would remain stable before the second-level treatment&#xD;
      conditions (pre-randomization phase), after the treatment and at follow-up in the control&#xD;
      group (A-CBT), whereas these measures would be reduced in the experimental group (VR-CET)&#xD;
      after treatment and at follow-up. In the second analysis block, it is expected that measures&#xD;
      of subjective anxiety will decrease as each exposure session progresses.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">February 2015</start_date>
  <completion_date type="Actual">March 2016</completion_date>
  <primary_completion_date type="Actual">September 2015</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>Double (Participant, Care Provider)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change from baseline in eating disorders symptomatology on the BN, DT and BD subscales of EDI-3 (Eating Disorders Inventory-3), at the end of the treatment and at six month follow-up</measure>
    <time_frame>Baseline (one assessment session before to the first second-level treatment session), week 3 (at the end of the last treatment session), and at the six-month follow-up</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Change from baseline in the frequency of binging and purging episodes using self-reports at the end of the treatment and at six month follow-up</measure>
    <time_frame>Baseline (daily along the two weeks before to the first second-level treatment session), daily along the two weeks after the last treatment session, and daily along the two weeks after six months follow-up</time_frame>
    <description>Binging and purging episodes will be self-registered by the participants of the two groups during the two weeks prior to beginning the second-level treatment sessions, during the two weeks after the end of the treatment sessions, and during two weeks after six-month follow-up</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change from baseline in food craving on the FCQ-T/S (Food Craving Questionnaire-Trait/State) at the end of the treatment and at six months follow-up</measure>
    <time_frame>Baseline (one assessment session before to the first second-level treatment session), week 3 (at the end of the last treatment session), and at the six-month follow-up</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change from baseline in anxiety on the State-Trait Anxiety Inventory at the end of the treatment and at six month follow-up</measure>
    <time_frame>Baseline (one assessment session before to the first second-level treatment session), week 3 (at the end of the last treatment session), and at the six-month follow-up</time_frame>
  </secondary_outcome>
  <other_outcome>
    <measure>Anxiety and food craving experienced during exposure to food-related VR environments on a visual analog scale from 0 to 100 (at pre-test)</measure>
    <time_frame>Pre-test prior to initiating the booster sessions (one session)</time_frame>
    <description>Participants assigned to the virtual reality based cue-exposure therapy condition will be exposed to 10 virtual foods in 4 different virtual environments (kitchen, dining-room, bedroom, and café) where they will be asked about their food craving and anxiety experienced in each situation to develop a proper exposure hierarchy according to the specific characteristics and needs of each patient.</description>
  </other_outcome>
  <other_outcome>
    <measure>Intrasession anxiety and food craving assessed using a visual analog scale from 0 to 100</measure>
    <time_frame>Up to 60 minutes. Baseline (prior to beginning the exposure task on each VR-CET session), every five minutes during the exposure task on each session, and at the end of the exposure task on each session</time_frame>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">60</enrollment>
  <condition>Bulimia Nervosa</condition>
  <condition>Binge-Eating Disorder</condition>
  <condition>Binge Eating</condition>
  <arm_group>
    <arm_group_label>VR based cue-exposure therapy</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Throughout the six sessions, participants (n=30) will be exposed to different VR environments related to binge behavior, according to a previously constructed hierarchy. During exposure, patients will face high risk situations to diminish or to extinguish the conditioned response of anxiety when exposed to food related cues. In each session, the patient will be exposed to the corresponding step of the hierarchy. During the exposure session, the patient can handle the virtual foods using the laptop's mouse but cannot eat the foods (exposure with response prevention). Exposure will end when the anxiety level decreased by 40% in relation to the level registered at the initiation of the exposure session or after 60 minutes of exposure.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Additional Cognitive-behavioral treatment</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Participants (n=30) in this condition will receive six CBT booster sessions (two sessions per week) over the course of three weeks to improve the output of treatment. CBT sessions are based on the approach described by by Eldredge and colleagues (Eldredge et al.,1997). In this treatment program, patients are trained to self-monitor their food patterns and to identify and manage thoughts, emotions, and environmental factors related to disrupted eating behaviors.</description>
  </arm_group>
  <intervention>
    <intervention_type>Behavioral</intervention_type>
    <intervention_name>VR based cue-exposure therapy</intervention_name>
    <description>Comparison of VR based cue-exposure therapy sessions and additional Cognitive-behavioral treatment sessions</description>
    <arm_group_label>VR based cue-exposure therapy</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Behavioral</intervention_type>
    <intervention_name>Additional Cognitive-behavioral treatment</intervention_name>
    <description>Comparison of VR based cue-exposure therapy sessions and additional Cognitive-behavioral treatment sessions</description>
    <arm_group_label>Additional Cognitive-behavioral treatment</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Diagnosis of bulimia nervosa or binge eating disorder according the DSM-5&#xD;
&#xD;
          -  Written and informed consent to participate&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Other concurrent severe mental disorders (substance use disorders, bipolar disorder,&#xD;
             psychosis)&#xD;
&#xD;
          -  Suicidal ideation&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>60 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>José Gutiérrez-Maldonado, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Barcelona</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Università Cattolica del Sacro Cuore</name>
      <address>
        <city>Milan</city>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Universitat de Barcelona</name>
      <address>
        <city>Barcelona</city>
        <zip>08035</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Italy</country>
    <country>Spain</country>
  </location_countries>
  <reference>
    <citation>Martinez-Mallen E, Castro-Fornieles J, Lazaro L, Moreno E, Morer A, Font E, Julien J, Vila M, Toro J. Cue exposure in the treatment of resistant adolescent bulimia nervosa. Int J Eat Disord. 2007 Nov;40(7):596-601. doi: 10.1002/eat.20423.</citation>
    <PMID>17607695</PMID>
  </reference>
  <reference>
    <citation>Toro J, Cervera M, Feliu MH, Garriga N, Jou M, Martinez E, Toro E. Cue exposure in the treatment of resistant bulimia nervosa. Int J Eat Disord. 2003 Sep;34(2):227-34. doi: 10.1002/eat.10186.</citation>
    <PMID>12898559</PMID>
  </reference>
  <reference>
    <citation>Fairburn, Christopher G; Wilson, G Terence. Binge eating: Nature, assessment, and treatment. New York: Guilford Press, 1993. NLM ID: 9216440 [Book]</citation>
  </reference>
  <verification_date>February 2017</verification_date>
  <study_first_submitted>September 4, 2014</study_first_submitted>
  <study_first_submitted_qc>September 9, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 11, 2014</study_first_posted>
  <last_update_submitted>February 8, 2017</last_update_submitted>
  <last_update_submitted_qc>February 8, 2017</last_update_submitted_qc>
  <last_update_posted type="Estimate">February 9, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Barcelona</investigator_affiliation>
    <investigator_full_name>Jose Gutierrez Maldonado</investigator_full_name>
    <investigator_title>Full Professor</investigator_title>
  </responsible_party>
  <keyword>Bulimia nervosa</keyword>
  <keyword>Binge eating disorder</keyword>
  <keyword>Food craving</keyword>
  <keyword>Anxiety</keyword>
  <keyword>Bingeing</keyword>
  <keyword>Cue Exposure Therapy</keyword>
  <keyword>Virtual Reality</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Bulimia</mesh_term>
    <mesh_term>Feeding and Eating Disorders</mesh_term>
    <mesh_term>Binge-Eating Disorder</mesh_term>
    <mesh_term>Bulimia 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/NCT02237300
org study id: PSI2011-28801
secondary id: PSI2011-28801
nct id: NCT02237300
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
Introduction: The purpose of this research is to develop a new component for
      cognitive-behavioral treatment (CBT), empirically validated, for binge eating behavior in
      patients with bulimia nervosa (BN) and binge eating disorder (BED), by means of cue-exposure
      therapy (CET) with virtual reality. While CBT is an effective treatment for these eating
      disorders, an important percentage of patients do not improve despite treatment. It is
      necessary to explore how to enhance the effectivity of usual treatments with the
      incorporation of new technologies and procedures. The innovation of this investigation is
      based on the use of VR for cue-exposure therapy, which has been found effective with patients
      resistant to conventional treatments (CBT and pharmacological intervention), and seeks to
      enhance this efficacy by increasing possibilities of generalization and providing more useful
      tools to clinicians, diminishing the logistic complications of the exposure to real cues
      (food).

      Participants: 60 patients with a diagnosis of BN or BED according the DSM-5 who had been
      proposed for participation in the study by their referral mental health's professional after
      conducting unsuccessfully a first level treatment (CBT structured intervention) at the
      clinical sites involved will participate in the study.

      Procedure: Participants with active episodes of binge eating (and purging, in the case of BN)
      during the last 2 weeks of the structured intervention of CBT will be provided with detailed
      information about the study. All patients who agree to participate in the study and who sign
      the informed consent form will be randomly assigned to one of the two second-level treatment
      conditions: virtual reality based cue-exposure therapy (VR-CET) or additional
      cognitive-behavioral treatment (A-CBT). Both second-level treatment conditions consist of six
      60-minute sessions that are held two times per week over a period of three weeks.

      In an interview setting, all of the participants will be administered several questionnaires
      (BN, DT and BD subscales of EDI-3, FCQ-T/S, and STAI-Y) and participants assigned to the
      VR-CET will also be exposed to various types of virtual foods in different virtual
      environments (kitchen, dining-room, bedroom, and café) where they will be asked about their
      food cravings and anxiety experienced in each situation to develop a proper exposure
      hierarchy according to the specific characteristics and needs of each patient.
Sample Sixty patients who have been diagnosed with BN or BED according to the Diagnostic and
      Statistical Manual of Mental Disorders Fifth Edition (DSM-5) and who have been found to be
      resistant to an initial structured program of CBT (Fairburn, Marcus, & Wilson, 1993) will
      participate in the study. Participants will be recruited from collaborating hospitals and
      health centers including Hospital de Bellvitge (Barcelona, Spain), Adult Mental Health Center
      of the Consorcio Sanitario de la Anoia (Igualada, Spain), Hospital Universitari Joan XXIII
      (Tarragona, Spain), Centro ABB (Tarragona, Spain) and the Instituto Auxologico Italiano
      (Milano, Italy). Suicidal ideation and diagnoses of other severe mental disorders (substance
      use disorders, bipolar disorder, psychosis) are exclusion criteria. Patients with active
      episodes of binge eating (and purging, in case of BN) during the last two weeks of the
      structured program of CBT will be considered for participation in the study. All prospective
      participants will be comprehensively informed about the characteristics of the study and will
      be required to sign an informed consent form. Authorization of the research ethics committees
      of the applicant organization (University of Barcelona) and the collaborating institutions
      will be required.

      Patients who agree to participate in the study will be randomly assigned to one of two
      second-level treatment conditions: the VR-CET group will receive cue-exposure sessions using
      VR environments (six 60-minute (maximum) sessions over the course of three weeks; two per
      week) and the A-CBT group will receive six additional sessions of the usual cognitive
      behavioral treatment. Consistent with the American Psychological Association and the CONSORT
      guideline recommendations regarding sample size in this type of research, 30 patients will be
      included in each group. If necessary, dropout cases will be replaced.

      Procedure At the end of the first level of treatment with the structured program of CBT, all
      patients will be assessed relative to their status and will complete several questionnaires
      (BN, DT and BD subscales of EDI-3, FCQ-T/S, and STAI-Y) (pre-randomization assessment).

      Those with active behavioral symptoms who agree to participate in the intervention study and
      who have signed the informed consent form will be randomly assigned to one of the two
      second-level treatment conditions: VR-CET or A-CBT sessions. Also, participants assigned to
      the VR-CET condition will be assessed through a validated VR-based cue exposure software
      (Gutiérrez-Maldonado, Pla-Sanjuanelo et al., 2016) in order to construct the exposure
      hierarchy of 3D interactive (environment and food) situations, used in the VR-CET sessions.
      For that, participants assigned to the VR-CET condition:

        1. Will be exposed to 30 graphic representations of different foods. The level of craving
           elicited by each food will be assessed by means of a visual analog scale (VAS) that
           ranges from 0 (not at all) to 100 (extreme).

        2. These participants will also be exposed to four graphic representations of different
           environments (kitchen, dining room, bedroom, and café). The level of craving elicited by
           each environment will be assessed by means of a VAS that ranges from 0 (not at all) to
           100 (extreme).

        3. They will be individually exposed to the ten different virtual foods assessed as
           eliciting the highest levels of craving in each of the four virtual environments
           (kitchen, dining room, bedroom, and café) for a total of 40 virtual situations from
           lowest to highest craving scores as previously registered in phases 1 and 2. Once in the
           virtual situation, the participant will be asked to sit at a virtual table where the
           food is placed. Once the participant sits, the time is measured. During the first 20
           seconds, the patient can handle the virtual food by means of the laptop's mouse but
           cannot eat the food. When time runs out, the levels of craving and anxiety will be
           assessed by means of visual analog scales that range from 0 (not at all) to 100
           (extreme). Virtual environments will be displayed by means of a 3D laptop with specific
           software that is capable of creating a stereoscopic effect that is duly processed by
           polarized glasses. Headphones will also be used. This assessment will be conducted in a
           quiet darkened room to increase the participant's immersion in the virtual scenarios.
           The therapist will remain behind the patient during the assessment so as not to
           interfere with the task but to be available in the event a participant requires
           assistance.

        4. Anxiety scores obtained from each of the 40 situations will be used to develop the
           exposure hierarchy that will be used in the VR-CET sessions.

      Virtual reality based cue-exposure therapy (VR-CET) sessions: There will be six 60-minute
      (maximum) exposure sessions (two sessions per week for three weeks). Participants (n=30) will
      be exposed to different VR environments related to binge behaviors, according to the
      previously constructed hierarchy. During exposure, patients will face high risk situations to
      diminish or extinguish the conditioned response of anxiety when exposed to food related cues.
      In each session, the patient will be exposed to the corresponding steps of the hierarchy.

      Additional cognitive-behavioral treatment (A-CBT) sessions: Participants (n=30) in this
      condition will receive six CBT booster sessions (twice weekly) over the course of three weeks
      to improve the output of treatment. CBT sessions are based on the approach described by
      Eldredge and colleagues (Eldredge et al., 1997). In this treatment, patients are trained to
      self-monitor their food patterns and to identify and manage thoughts, emotions, and
      environmental factors related to disrupted eating behaviors.

      VR based cue-exposure booster sessions The cue-exposure procedure used in this study is an
      adaptation of the cue-exposure treatment for BN proposed by Martinez-Mallen et al. (2007).
      Exposure sessions will be conducted individually in a quiet, darkened room. In each session,
      the participant will sit in front of a 3D laptop with software that is capable of creating a
      stereoscopic effect that is duly processed by polarized glasses. Headphones with active noise
      cancellation will also be used to expose the participant to the auditory stimuli in the
      virtual environments and, at the same time, to isolate the patient from external noises.
      Participants can interact within the virtual environments in real time. They can move around
      the scenarios, sit at a table, and they can handle foods displayed using the keyboard and the
      laptop's mouse.

      During the first minutes of the session, patients will be reminded of the purpose of the
      exposure, that is, to place them in contact with food despite the high levels of anxiety they
      experience. Doubts and questions raised by the participants will be attended to at this time.
      The participants will be exposed to the corresponding virtual environments and foods based on
      the previously established hierarchy. Along the VR-CET sessions, craving and anxiety levels
      were assessed periodically. Exposure will terminate when subjective anxiety has decreased a
      40% in relation to the level registered at the initiation of the exposure session or after 60
      minutes. Once the anxiety level has decreased significantly, the patient will be exposed to
      the next level in the hierarchy. In the event the session terminates before the anxiety level
      has been sufficiently reduced in the virtual situations, the patients will be exposed to the
      same situation in the following session. Subjective craving and anxiety will be recorded
      using visual analogic scales (VAS) that range from 0 (not at all) to 100 (extreme) at the
      beginning, every minute, and at the end of the virtual scenario exposures. During exposure,
      the therapist will remain behind the patient and will only intervene if instruction is needed
      or if the patient needs assistance.

      Assessment During each VR-CET session, subjective craving and anxiety will be assessed using
      VAS (range from 0 to 100) and will be recorded at the beginning, every minute, and at the end
      of the exposure.

      The following questionnaires will be administered to the participants of the two groups
      before initiating treatment (pre-randomization phase), at the end of the second level-level
      treatment conditions, and at the six-month follow-up: STAI-Y (State-Trait Anxiety
      Inventory-Form Y), BN, DT and BD subscales of EDI-3 (Eating Disorders Inventory-3) and
      FCQ-T/S (Food Craving Questionnaire-Trait/State).

      Finally, outcome assessment for core behavioural features included frequency (i.e., number)
      of binge eating episodes and purging during the two weeks prior to beginning the second-level
      treatment conditions, during the two weeks after the end of the intervention, and during two
      weeks after six-month follow-up.

      Data analyses Mixed between-within subject analysis of variance will be conducted.
      Between-subject variable refers to both conditions, the VR-CET versus A-CBT. The
      within-subject variable refers to the assessment time: prior to beginning the second-level
      treatment conditions (both VR-CET and A-CBT conditions), at the end of the treatment, and at
      the six-month follow-up. Thus, comparisons between results obtained by both groups before
      treatment, after treatment and at follow-up for each of the assessed measures will be
      conducted. Using a similar analysis, anxiety measures registered during each exposure session
      will also be compared.

      A significant interaction between condition (VR-CET vs. A-CBT) and time is expected in the
      first block of analyses. This would indicate that the results of the questionnaires as well
      as the number of binges and purges would remain stable before the second-level treatment
      conditions (pre-randomization phase), after the treatment and at follow-up in the control
      group (A-CBT), whereas these measures would be reduced in the experimental group (VR-CET)
      after treatment and at follow-up. In the second analysis block, it is expected that measures
      of subjective anxiety will decrease as each exposure session progresses.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Double (Participant, Care Provider)
measure: Change from baseline in eating disorders symptomatology on the BN, DT and BD subscales of EDI-3 (Eating Disorders Inventory-3), at the end of the treatment and at six month follow-up
time frame: Baseline (one assessment session before to the first second-level treatment session), week 3 (at the end of the last treatment session), and at the six-month follow-up
measure: Change from baseline in the frequency of binging and purging episodes using self-reports at the end of the treatment and at six month follow-up
time frame: Baseline (daily along the two weeks before to the first second-level treatment session), daily along the two weeks after the last treatment session, and daily along the two weeks after six months follow-up
description: Binging and purging episodes will be self-registered by the participants of the two groups during the two weeks prior to beginning the second-level treatment sessions, during the two weeks after the end of the treatment sessions, and during two weeks after six-month follow-up
measure: Change from baseline in food craving on the FCQ-T/S (Food Craving Questionnaire-Trait/State) at the end of the treatment and at six months follow-up
time frame: Baseline (one assessment session before to the first second-level treatment session), week 3 (at the end of the last treatment session), and at the six-month follow-up
measure: Change from baseline in anxiety on the State-Trait Anxiety Inventory at the end of the treatment and at six month follow-up
time frame: Baseline (one assessment session before to the first second-level treatment session), week 3 (at the end of the last treatment session), and at the six-month follow-up
measure: Anxiety and food craving experienced during exposure to food-related VR environments on a visual analog scale from 0 to 100 (at pre-test)
time frame: Pre-test prior to initiating the booster sessions (one session)
description: Participants assigned to the virtual reality based cue-exposure therapy condition will be exposed to 10 virtual foods in 4 different virtual environments (kitchen, dining-room, bedroom, and café) where they will be asked about their food craving and anxiety experienced in each situation to develop a proper exposure hierarchy according to the specific characteristics and needs of each patient.
measure: Intrasession anxiety and food craving assessed using a visual analog scale from 0 to 100
time frame: Up to 60 minutes. Baseline (prior to beginning the exposure task on each VR-CET session), every five minutes during the exposure task on each session, and at the end of the exposure task on each session
arm group label: VR based cue-exposure therapy
arm group type: Experimental
description: Throughout the six sessions, participants (n=30) will be exposed to different VR environments related to binge behavior, according to a previously constructed hierarchy. During exposure, patients will face high risk situations to diminish or to extinguish the conditioned response of anxiety when exposed to food related cues. In each session, the patient will be exposed to the corresponding step of the hierarchy. During the exposure session, the patient can handle the virtual foods using the laptop's mouse but cannot eat the foods (exposure with response prevention). Exposure will end when the anxiety level decreased by 40% in relation to the level registered at the initiation of the exposure session or after 60 minutes of exposure.
arm group label: Additional Cognitive-behavioral treatment
arm group type: Active Comparator
description: Participants (n=30) in this condition will receive six CBT booster sessions (two sessions per week) over the course of three weeks to improve the output of treatment. CBT sessions are based on the approach described by by Eldredge and colleagues (Eldredge et al.,1997). In this treatment program, patients are trained to self-monitor their food patterns and to identify and manage thoughts, emotions, and environmental factors related to disrupted eating behaviors.
intervention type: Behavioral
intervention name: VR based cue-exposure therapy
description: Comparison of VR based cue-exposure therapy sessions and additional Cognitive-behavioral treatment sessions
arm group label: VR based cue-exposure therapy
intervention type: Behavioral
intervention name: Additional Cognitive-behavioral treatment
description: Comparison of VR based cue-exposure therapy sessions and additional Cognitive-behavioral treatment sessions
arm group label: Additional Cognitive-behavioral treatment
criteria: 
gender: All
minimum age: 18 Years
maximum age: 60 Years
healthy volunteers: No
last name: José Gutiérrez-Maldonado, PhD
role: Principal Investigator
affiliation: University of Barcelona
facility: 
facility: 
country: Italy
country: Spain
citation: Martinez-Mallen E, Castro-Fornieles J, Lazaro L, Moreno E, Morer A, Font E, Julien J, Vila M, Toro J. Cue exposure in the treatment of resistant adolescent bulimia nervosa. Int J Eat Disord. 2007 Nov;40(7):596-601. doi: 10.1002/eat.20423.
PMID: 17607695
citation: Toro J, Cervera M, Feliu MH, Garriga N, Jou M, Martinez E, Toro E. Cue exposure in the treatment of resistant bulimia nervosa. Int J Eat Disord. 2003 Sep;34(2):227-34. doi: 10.1002/eat.10186.
PMID: 12898559
citation: Fairburn, Christopher G; Wilson, G Terence. Binge eating: Nature, assessment, and treatment. New York: Guilford Press, 1993. NLM ID: 9216440 [Book]
responsible party type: Principal Investigator
investigator affiliation: University of Barcelona
investigator full name: Jose Gutierrez Maldonado
investigator title: Full Professor
mesh term: Bulimia
mesh term: Feeding and Eating Disorders
mesh term: Binge-Eating Disorder
mesh term: Bulimia Nervosa
sharing ipd: No