<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/NCT04405440</url>
  </required_header>
  <id_info>
    <org_study_id>S62060</org_study_id>
    <nct_id>NCT04405440</nct_id>
  </id_info>
  <brief_title>Excessive Avoidance Behaviors in Anorexia Nervosa: the Role of Reward</brief_title>
  <official_title>Excessive Avoidance Behaviors in Anorexia Nervosa: the Role of Reward</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Bram Vervliet</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>KU Leuven</source>
  <oversight_info>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study investigates excessive avoidance behaviors in patients with a diagnosis of&#xD;
      Anorexia Nervosa (AN) compared to a healthy control group. The study further examines the&#xD;
      role of reward (relief) as a putative factor in maintaining excessive avoidance behaviors in&#xD;
      AN.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Anorexia Nervosa (AN) is a life-threatening mental disease with a disappointing treatment&#xD;
      outcome. Fear of weight gain and diet restrictions are considered the core symptoms of AN.&#xD;
      Although from a diagnostic perspective AN is conceptualized as an eating-related disorder&#xD;
      connected to an extremely low Body Mass Index (BMI) and body image distortion, AN might&#xD;
      represent a specific phenotype of anxiety disorders characterized by tenacious avoidance&#xD;
      behaviors, especially the restrictive subtype. To date, avoidance in AN is often investigated&#xD;
      as a general personality trait (e.g. harm avoidance) but poorly examined in its behavioral&#xD;
      form (which is life-threatening, such as food-avoidance). Hence, the investigators will&#xD;
      perform a systematic investigation of excessive avoidance behaviors within a laboratory&#xD;
      setting. Within a learning perspective, the investigators will investigate excessive&#xD;
      avoidance in a group of 30 AN patients and 30 healthy volunteers. To achieve this, a&#xD;
      well-validated avoidance paradigm will be used. Most critically, the investigators will&#xD;
      examine whether patients with a diagnosis of anorexia nervosa show persistent avoidance&#xD;
      behaviors compared to a control group. Additionally, the investigators will examine if, in&#xD;
      the anorexia group, higher subjective relief to successful omissions of negative events&#xD;
      during avoidance learning predicts persistent (excessive) avoidance behaviors after fear&#xD;
      extinction.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">May 1, 2019</start_date>
  <completion_date type="Anticipated">September 1, 2021</completion_date>
  <primary_completion_date type="Anticipated">May 1, 2021</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Case-Control</observational_model>
    <time_perspective>Cross-Sectional</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Button clicks during a red cue will be recorded as a measure of avoidance (binary response)</measure>
    <time_frame>through study completion, an average of 1 year</time_frame>
    <description>To investigate whether, compared to healthy controls, individuals with a diagnosis of anorexia nervosa show excessive avoidance behaviors (frequent clicking to prevent the aversive stimulus). Repeated measure ANOVA (analysis of variance) will be employed to evaluate differences between groups. If data will violate the assumption of normality, mixed or generalize methods will be used.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Relief pleasantness ratings (Visual Analog Scale, from neutral [0] to very pleasant [100])</measure>
    <time_frame>through study completion, an average of 1 year</time_frame>
    <description>To investigate whether, compared to healthy controls, individuals with a diagnosis of anorexia nervosa show higher relief pleasantness during the omission of the aversive stimuli. The investigators will also test if such responses predict a return in avoidance behaviors (button click) after fear has been extinguished. Repeated measure ANOVA (analysis of variance) and multiple linear regressions will be employed to evaluate differences between groups. If data will violate the assumption of normality mixed or generalize methods will be used.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>US-Expectancy ratings (Likert scale from 0:no picture to 10:certainly a picture)</measure>
    <time_frame>through study completion, an average of 1 year</time_frame>
    <description>To investigate whether, compared to healthy controls, individuals with a diagnosis of anorexia nervosa show higher US-expectancies during both avoidance learning and fear extinction learning. Repeated measure ANOVA (analysis of variance) will be employed to evaluate differences between groups. If data will violate the assumption of normality mixed or generalize methods will be used.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Eating Disorders Inventory [EDI]</measure>
    <time_frame>through study completion, an average of 1 year</time_frame>
    <description>Higher scores at the EDI, and especially to the drive for thinness subscale, correlate with higher avoidance actions.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Distress Tolerance Scale [DTS]</measure>
    <time_frame>through study completion, an average of 1 year</time_frame>
    <description>Lower scores at the DTS correlate with higher relief and higher avoidance actions</description>
  </secondary_outcome>
  <number_of_groups>2</number_of_groups>
  <enrollment type="Anticipated">100</enrollment>
  <condition>Eating Disorders</condition>
  <condition>Anxiety</condition>
  <condition>Anorexia Nervosa</condition>
  <arm_group>
    <arm_group_label>Healthy controls</arm_group_label>
    <description>The healthy control group will perform a well-validated avoidance (behavioral) task and will fill in some questionnaires about eating behaviors, emotions, and feelings.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Anorexia Nervosa patients</arm_group_label>
    <description>As the healthy controls, the participants of the anorexia nervosa group will perform the same behavioral task and will fill in the same questionnaires</description>
  </arm_group>
  <intervention>
    <intervention_type>Behavioral</intervention_type>
    <intervention_name>Behavioral avoidance task</intervention_name>
    <description>Behavioral task able to measure avoidance actions, US-expectancy, and reward-related indexes in different learning times</description>
    <arm_group_label>Anorexia Nervosa patients</arm_group_label>
    <arm_group_label>Healthy controls</arm_group_label>
  </intervention>
  <eligibility>
    <study_pop>
      <textblock>
        The anorexia patients are recruited from a primary care clinic. Healthy controls are&#xD;
        recruited from the general population&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  For the AN group, patients need to be physically strong and sufficiently emotionally&#xD;
             stable&#xD;
&#xD;
          -  For the healthy group, the investigators will recruit participants without a previous&#xD;
             or current history of psychiatric, cardiovascular, neurological or other relevant&#xD;
             disorder&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  For the AN group, the investigators will exclude patients who are insufficiently&#xD;
             emotionally stable and/or physically weak to participate in the study as estimated by&#xD;
             the treating physicians of the units on which the patients are admitted&#xD;
&#xD;
          -  Insufficient verbal skills to understand the questionnaires and the computer task&#xD;
&#xD;
          -  Participants who are pregnant or breastfeeding&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>40 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Laurence Claes, Prof. Dr.</last_name>
    <role>Principal Investigator</role>
    <affiliation>KU Leuven</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Laurence Claes, Prof. Dr.</last_name>
    <phone>+32 16 32 61 33</phone>
    <email>laurence.claes@kuleuven.be</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Bram Vervliet, Prof. Dr.</last_name>
    <email>bram.vervliet@kuleuven.be</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Psychiatry | UZ Leuven campus Gasthuisberg</name>
      <address>
        <city>Leuven</city>
        <zip>3000</zip>
        <country>Belgium</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Laurence Claes, Prof. Dr.</last_name>
      <email>laurence.claes@kuleuven.be</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>University of KU Leuven, Faculteit Psychologie en Pedagogische Wetenschappen</name>
      <address>
        <city>Leuven</city>
        <zip>3000</zip>
        <country>Belgium</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Laurence Claes, Prof. Dr.</last_name>
      <phone>32 16 32 61 33</phone>
      <email>laurence.claes@kuleuven.be</email>
    </contact>
    <contact_backup>
      <last_name>Bram Vervliet, Prof. Dr.</last_name>
      <email>bram.vervliet@kuleuven.be</email>
    </contact_backup>
  </location>
  <location_countries>
    <country>Belgium</country>
  </location_countries>
  <reference>
    <citation>Kaye WH, Bulik CM, Thornton L, Barbarich N, Masters K. Comorbidity of anxiety disorders with anorexia and bulimia nervosa. Am J Psychiatry. 2004 Dec;161(12):2215-21. doi: 10.1176/appi.ajp.161.12.2215.</citation>
    <PMID>15569892</PMID>
  </reference>
  <reference>
    <citation>Godart NT, Flament MF, Lecrubier Y, Jeammet P. Anxiety disorders in anorexia nervosa and bulimia nervosa: co-morbidity and chronology of appearance. Eur Psychiatry. 2000 Feb;15(1):38-45. doi: 10.1016/s0924-9338(00)00212-1.</citation>
    <PMID>10713801</PMID>
  </reference>
  <reference>
    <citation>Koskina A, Campbell IC, Schmidt U. Exposure therapy in eating disorders revisited. Neurosci Biobehav Rev. 2013 Feb;37(2):193-208. doi: 10.1016/j.neubiorev.2012.11.010. Epub 2012 Nov 29.</citation>
    <PMID>23201859</PMID>
  </reference>
  <reference>
    <citation>Murray SB, Loeb KL, Le Grange D. Dissecting the Core Fear in Anorexia Nervosa: Can We Optimize Treatment Mechanisms? JAMA Psychiatry. 2016 Sep 1;73(9):891-2. doi: 10.1001/jamapsychiatry.2016.1623. No abstract available.</citation>
    <PMID>27463780</PMID>
  </reference>
  <reference>
    <citation>Murray SB, Strober M, Craske MG, Griffiths S, Levinson CA, Strigo IA. Fear as a translational mechanism in the psychopathology of anorexia nervosa. Neurosci Biobehav Rev. 2018 Dec;95:383-395. doi: 10.1016/j.neubiorev.2018.10.013. Epub 2018 Oct 28.</citation>
    <PMID>30392878</PMID>
  </reference>
  <reference>
    <citation>Wierenga CE, Bischoff-Grethe A, Melrose AJ, Irvine Z, Torres L, Bailer UF, Simmons A, Fudge JL, McClure SM, Ely A, Kaye WH. Hunger does not motivate reward in women remitted from anorexia nervosa. Biol Psychiatry. 2015 Apr 1;77(7):642-52. doi: 10.1016/j.biopsych.2014.09.024. Epub 2014 Oct 22.</citation>
    <PMID>25481622</PMID>
  </reference>
  <reference>
    <citation>Park RJ, Godier LR, Cowdrey FA. Hungry for reward: How can neuroscience inform the development of treatment for Anorexia Nervosa? Behav Res Ther. 2014 Nov;62:47-59. doi: 10.1016/j.brat.2014.07.007. Epub 2014 Jul 26.</citation>
    <PMID>25151600</PMID>
  </reference>
  <verification_date>May 2020</verification_date>
  <study_first_submitted>November 28, 2019</study_first_submitted>
  <study_first_submitted_qc>May 27, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">May 28, 2020</study_first_posted>
  <last_update_submitted>May 27, 2020</last_update_submitted>
  <last_update_submitted_qc>May 27, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">May 28, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>KU Leuven</investigator_affiliation>
    <investigator_full_name>Bram Vervliet</investigator_full_name>
    <investigator_title>Principal Investigator Prof. Dr. Bram Vervliet</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Anorexia</mesh_term>
    <mesh_term>Feeding and Eating Disorders</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/NCT04405440
org study id: S62060
nct id: NCT04405440
lead sponsor: 
is fda regulated device: No
This study investigates excessive avoidance behaviors in patients with a diagnosis of
      Anorexia Nervosa (AN) compared to a healthy control group. The study further examines the
      role of reward (relief) as a putative factor in maintaining excessive avoidance behaviors in
      AN.
Anorexia Nervosa (AN) is a life-threatening mental disease with a disappointing treatment
      outcome. Fear of weight gain and diet restrictions are considered the core symptoms of AN.
      Although from a diagnostic perspective AN is conceptualized as an eating-related disorder
      connected to an extremely low Body Mass Index (BMI) and body image distortion, AN might
      represent a specific phenotype of anxiety disorders characterized by tenacious avoidance
      behaviors, especially the restrictive subtype. To date, avoidance in AN is often investigated
      as a general personality trait (e.g. harm avoidance) but poorly examined in its behavioral
      form (which is life-threatening, such as food-avoidance). Hence, the investigators will
      perform a systematic investigation of excessive avoidance behaviors within a laboratory
      setting. Within a learning perspective, the investigators will investigate excessive
      avoidance in a group of 30 AN patients and 30 healthy volunteers. To achieve this, a
      well-validated avoidance paradigm will be used. Most critically, the investigators will
      examine whether patients with a diagnosis of anorexia nervosa show persistent avoidance
      behaviors compared to a control group. Additionally, the investigators will examine if, in
      the anorexia group, higher subjective relief to successful omissions of negative events
      during avoidance learning predicts persistent (excessive) avoidance behaviors after fear
      extinction.
observational model: Case-Control
time perspective: Cross-Sectional
measure: Button clicks during a red cue will be recorded as a measure of avoidance (binary response)
time frame: through study completion, an average of 1 year
description: To investigate whether, compared to healthy controls, individuals with a diagnosis of anorexia nervosa show excessive avoidance behaviors (frequent clicking to prevent the aversive stimulus). Repeated measure ANOVA (analysis of variance) will be employed to evaluate differences between groups. If data will violate the assumption of normality, mixed or generalize methods will be used.
measure: Relief pleasantness ratings (Visual Analog Scale, from neutral [0] to very pleasant [100])
time frame: through study completion, an average of 1 year
description: To investigate whether, compared to healthy controls, individuals with a diagnosis of anorexia nervosa show higher relief pleasantness during the omission of the aversive stimuli. The investigators will also test if such responses predict a return in avoidance behaviors (button click) after fear has been extinguished. Repeated measure ANOVA (analysis of variance) and multiple linear regressions will be employed to evaluate differences between groups. If data will violate the assumption of normality mixed or generalize methods will be used.
measure: US-Expectancy ratings (Likert scale from 0:no picture to 10:certainly a picture)
time frame: through study completion, an average of 1 year
description: To investigate whether, compared to healthy controls, individuals with a diagnosis of anorexia nervosa show higher US-expectancies during both avoidance learning and fear extinction learning. Repeated measure ANOVA (analysis of variance) will be employed to evaluate differences between groups. If data will violate the assumption of normality mixed or generalize methods will be used.
measure: Eating Disorders Inventory [EDI]
time frame: through study completion, an average of 1 year
description: Higher scores at the EDI, and especially to the drive for thinness subscale, correlate with higher avoidance actions.
measure: Distress Tolerance Scale [DTS]
time frame: through study completion, an average of 1 year
description: Lower scores at the DTS correlate with higher relief and higher avoidance actions
arm group label: Healthy controls
description: The healthy control group will perform a well-validated avoidance (behavioral) task and will fill in some questionnaires about eating behaviors, emotions, and feelings.
arm group label: Anorexia Nervosa patients
description: As the healthy controls, the participants of the anorexia nervosa group will perform the same behavioral task and will fill in the same questionnaires
intervention type: Behavioral
intervention name: Behavioral avoidance task
description: Behavioral task able to measure avoidance actions, US-expectancy, and reward-related indexes in different learning times
arm group label: Anorexia Nervosa patients
arm group label: Healthy controls
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: 40 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Laurence Claes, Prof. Dr.
role: Principal Investigator
affiliation: KU Leuven
last name: Laurence Claes, Prof. Dr.
phone: +32 16 32 61 33
email: laurence.claes@kuleuven.be
last name: Bram Vervliet, Prof. Dr.
email: bram.vervliet@kuleuven.be
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
contact backup: 
country: Belgium
citation: Kaye WH, Bulik CM, Thornton L, Barbarich N, Masters K. Comorbidity of anxiety disorders with anorexia and bulimia nervosa. Am J Psychiatry. 2004 Dec;161(12):2215-21. doi: 10.1176/appi.ajp.161.12.2215.
PMID: 15569892
citation: Godart NT, Flament MF, Lecrubier Y, Jeammet P. Anxiety disorders in anorexia nervosa and bulimia nervosa: co-morbidity and chronology of appearance. Eur Psychiatry. 2000 Feb;15(1):38-45. doi: 10.1016/s0924-9338(00)00212-1.
PMID: 10713801
citation: Koskina A, Campbell IC, Schmidt U. Exposure therapy in eating disorders revisited. Neurosci Biobehav Rev. 2013 Feb;37(2):193-208. doi: 10.1016/j.neubiorev.2012.11.010. Epub 2012 Nov 29.
PMID: 23201859
citation: Murray SB, Loeb KL, Le Grange D. Dissecting the Core Fear in Anorexia Nervosa: Can We Optimize Treatment Mechanisms? JAMA Psychiatry. 2016 Sep 1;73(9):891-2. doi: 10.1001/jamapsychiatry.2016.1623. No abstract available.
PMID: 27463780
citation: Murray SB, Strober M, Craske MG, Griffiths S, Levinson CA, Strigo IA. Fear as a translational mechanism in the psychopathology of anorexia nervosa. Neurosci Biobehav Rev. 2018 Dec;95:383-395. doi: 10.1016/j.neubiorev.2018.10.013. Epub 2018 Oct 28.
PMID: 30392878
citation: Wierenga CE, Bischoff-Grethe A, Melrose AJ, Irvine Z, Torres L, Bailer UF, Simmons A, Fudge JL, McClure SM, Ely A, Kaye WH. Hunger does not motivate reward in women remitted from anorexia nervosa. Biol Psychiatry. 2015 Apr 1;77(7):642-52. doi: 10.1016/j.biopsych.2014.09.024. Epub 2014 Oct 22.
PMID: 25481622
citation: Park RJ, Godier LR, Cowdrey FA. Hungry for reward: How can neuroscience inform the development of treatment for Anorexia Nervosa? Behav Res Ther. 2014 Nov;62:47-59. doi: 10.1016/j.brat.2014.07.007. Epub 2014 Jul 26.
PMID: 25151600
responsible party type: Sponsor-Investigator
investigator affiliation: KU Leuven
investigator full name: Bram Vervliet
investigator title: Principal Investigator Prof. Dr. Bram Vervliet
mesh term: Anorexia
mesh term: Feeding and Eating Disorders
mesh term: Anorexia Nervosa
sharing ipd: No