<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/NCT03019081</url>
  </required_header>
  <id_info>
    <org_study_id>2015-013</org_study_id>
    <nct_id>NCT03019081</nct_id>
  </id_info>
  <brief_title>Augmented Interoceptive Exposure Training in Anorexia Nervosa</brief_title>
  <official_title>Augmented Interoceptive Exposure Training for the Fear of Food in Anorexia Nervosa</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Laureate Institute for Brain Research, Inc.</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Brain &amp; Behavior Research Foundation</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Laureate Institute for Brain Research, Inc.</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The researchers propose to utilize a pharmacological approach involving infusions of the&#xD;
      sympathomimetic agent isoproterenol to repeatedly trigger cardiorespiratory sensations and&#xD;
      anxiety during meal anticipation, to facilitate the development of tolerance or a reduction&#xD;
      of the anxiety/fear response in individuals with anorexia nervosa. The investigators aim to&#xD;
      conduct a proof of principle study to assess for evidence of initial efficacy of this new&#xD;
      treatment approach. As a comparator condition, the researchers propose using repeated&#xD;
      administration of saline infusions.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Individuals with anorexia nervosa (AN) are afraid to eat. Moreover, anxiety is a prominent&#xD;
      symptom in AN, with anxiety disorders frequently preceding and/or co-occurring with the&#xD;
      illness, and with an increased prevalence of anxiety disorders in first-degree family&#xD;
      members. Pre-meal anxiety poses a frequent challenge in treatment settings which require&#xD;
      adherence to strict meal plans, particularly since it is associated with lower caloric&#xD;
      intake. While problematic under current treatment settings, this illness characteristic also&#xD;
      provides a potentially important therapeutic target. Unfortunately, straightforward pre-meal&#xD;
      treatment with typically effective anxiolytic medicines such as alprazolam are ineffective in&#xD;
      individuals with AN, nor do they increase caloric intake. By contrast, cognitive behavioral&#xD;
      therapies for anorexia nervosa utilizing exposure therapy, the most effective psychological&#xD;
      intervention for anxiety and anxiety disorders, can promote food intake and increase weight&#xD;
      in AN. However, such treatments are slow and have less than ideal response rates, suggesting&#xD;
      that they could benefit from further optimization. Exposure therapy involves helping patients&#xD;
      to voluntarily engage in repeated and sometimes prolonged confrontation with the stimulus&#xD;
      that disproportionately provokes the individual's fear. The aim of this practice is to&#xD;
      facilitate the development of tolerance or a reduction of the anxiety/fear response that has&#xD;
      become conditionally associated with the relevant stimulus, thereby demonstrating to patients&#xD;
      that they can learn to manage effectively in the face of anxiety. In the case of anorexia&#xD;
      nervosa, the repeated presentation of food and food cues (mental imagery, pictures, smells)&#xD;
      elicits distress and facilitates the subsequent development of tolerance of these symptoms.&#xD;
      Unfortunately, the effect size of this intervention in AN is relatively small. Here, the&#xD;
      researchers investigate whether the use of an acute pharmacological intervention in the&#xD;
      context of aversive learning to enhance exposure training can reduce anxiety associated with&#xD;
      eating in individuals with anorexia nervosa.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date>January 2017</start_date>
  <completion_date type="Anticipated">July 2023</completion_date>
  <primary_completion_date type="Anticipated">August 2022</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, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Anxiety</measure>
    <time_frame>Immediately after drug/placebo infusion</time_frame>
    <description>Visual analogue self report rating scale</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Sensation intensity</measure>
    <time_frame>Immediately after drug/placebo infusion</time_frame>
    <description>Heartbeat and breathing sensation intensity via self report rating scale</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Anxiety sensitivity index</measure>
    <time_frame>Immediately after drug/placebo infusion</time_frame>
    <description>Self report rating scale</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Positive and Negative Affect</measure>
    <time_frame>Immediately after drug/placebo infusion</time_frame>
    <description>Self report rating scale</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Inventory of Depression and Anxiety</measure>
    <time_frame>Immediately after drug/placebo infusion</time_frame>
    <description>Self report rating scale</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Multidimensional Assessment of Interoceptive Awareness</measure>
    <time_frame>Immediately after drug/placebo infusion</time_frame>
    <description>Self report rating scale</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">25</enrollment>
  <condition>Anorexia Nervosa</condition>
  <arm_group>
    <arm_group_label>Anorexia nervosa-study drug</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Drug: Isoproterenol Intravenous infusions of isoproterenol, delivered in a randomized double blinded order, in each participant. The isoproterenol dose will range from 0.1 micrograms to 4.0 micrograms and exposure during each visit will not exceed 25.0 micrograms. Participants will rate the experience of heartbeat and breathing sensations as well as anxiety induced by the infusion.&#xD;
Other Names: Isuprel</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Anorexia nervosa-placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Drug: Normal Saline Intravenous infusions of normal saline, delivered in a randomized double blinded order, in each participant. Participants will rate the experience of heartbeat and breathing sensations as well as anxiety induced by the infusion.&#xD;
Other Names:&#xD;
Saline</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Isoproterenol</intervention_name>
    <description>The goal of this experiment is to use isoproterenol in the context of inhibitory fear learning to reduce eating-related anxiety in AN, and to explore whether these changes are related to interoceptive awareness and autonomic reactivity.</description>
    <arm_group_label>Anorexia nervosa-study drug</arm_group_label>
    <other_name>Isuprel</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>placebo</intervention_name>
    <description>placebo</description>
    <arm_group_label>Anorexia nervosa-placebo</arm_group_label>
    <other_name>Normal Saline</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Must have a body mass index between 17 to 35 kg/m²&#xD;
&#xD;
          2. Must be able to provide written informed consent and must have sufficient proficiency&#xD;
             in the English language to understand and complete interviews, questionnaires, and all&#xD;
             other study procedures.&#xD;
&#xD;
          3. Must be capable of performing all tasks during each session of the experiment.&#xD;
&#xD;
        Inclusion criteria (AN participants, n = 50):&#xD;
&#xD;
        Participants (ages 18 to 40) must meet Diagnostic and Statistical Manual (DSM 5) criteria&#xD;
        for Anorexia Nervosa, either current or lifetime, or have an Eating Disorder Screen (SCOFF)&#xD;
        score ≥ 2 and a current BMI of 17 or greater. Selected medications are allowed, including&#xD;
        selective serotonin reuptake inhibitors and benzodiazepines. Mood stabilizers and&#xD;
        antipsychotic medications are excluded.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. No telephone or limited access to a telephone&#xD;
&#xD;
          2. Has any of the following DSM 5 disorders:&#xD;
&#xD;
               1. Schizophrenia Spectrum and Other Psychotic Disorders&#xD;
&#xD;
               2. Bipolar and Related Disorders&#xD;
&#xD;
               3. Antisocial Personality Disorder&#xD;
&#xD;
          3. Active suicidal ideation with intent or plan&#xD;
&#xD;
          4. Obesity with a body mass index &gt; 35 preventing scanner entry.&#xD;
&#xD;
          5. Illicit stimulant drugs consumed within the past week including methamphetamine or&#xD;
             cocaine, assessed via urine drug screen&#xD;
&#xD;
          6. Active drug or alcohol dependence, or active binge drinking within the last month&#xD;
&#xD;
          7. Pregnancy as detected by a urine test&#xD;
&#xD;
          8. Prescription of a medication outside of the accepted range, as determined by best&#xD;
             clinical practices and current research.&#xD;
&#xD;
          9. Change in the dose or prescription of a medication within the 3 weeks before enrolling&#xD;
             in the study that could affect subjective responses, e.g., anxiolytics or&#xD;
             antidepressants.&#xD;
&#xD;
         10. Presence of unstable cardiac, vascular, pulmonary, gastrointestinal, endocrine,&#xD;
             neurologic, hematologic, rheumatologic, or metabolic disease; or any other condition&#xD;
             that, in the opinion of the investigator, would make participation not be in the best&#xD;
             interest (e.g., compromise the well-being) of the subject or that could prevent,&#xD;
             limit, or confound the protocol-specified assessments.&#xD;
&#xD;
         11. Non-correctable vision or hearing problems.&#xD;
&#xD;
         12. Systolic blood pressure &gt; 160 mmHg&#xD;
&#xD;
         13. Diastolic blood pressure &gt; 100 mmHg&#xD;
&#xD;
        Additional AN-specific exclusion criteria (AN participants):&#xD;
&#xD;
          1. Any AN individual reporting a history of cardiac or respiratory disease&#xD;
&#xD;
          2. AN with 12-lead EKG abnormalities other than bradycardia or occasional premature&#xD;
             ventricular complexes (PVCs); those with severe bradycardia, e.g. heart rate less than&#xD;
             40 bpm will be excluded.&#xD;
&#xD;
          3. AN reporting a seizure within the past year&#xD;
&#xD;
          4. Active antipsychotic, mood stabilizer, lithium, stimulant, or wellbutrin medication&#xD;
             prescription.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>40 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Sahib S Khalsa, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Laureate Institute for Brain Research</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Laureate Institute for Brain Research</name>
      <address>
        <city>Tulsa</city>
        <state>Oklahoma</state>
        <zip>74136</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>April 2022</verification_date>
  <study_first_submitted>January 9, 2017</study_first_submitted>
  <study_first_submitted_qc>January 10, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 12, 2017</study_first_posted>
  <last_update_submitted>April 9, 2022</last_update_submitted>
  <last_update_submitted_qc>April 9, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">April 12, 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>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Isoproterenol</mesh_term>
  </intervention_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/NCT03019081
org study id: 2015-013
nct id: NCT03019081
lead sponsor: 
collaborator: 
has dmc: No
The researchers propose to utilize a pharmacological approach involving infusions of the
      sympathomimetic agent isoproterenol to repeatedly trigger cardiorespiratory sensations and
      anxiety during meal anticipation, to facilitate the development of tolerance or a reduction
      of the anxiety/fear response in individuals with anorexia nervosa. The investigators aim to
      conduct a proof of principle study to assess for evidence of initial efficacy of this new
      treatment approach. As a comparator condition, the researchers propose using repeated
      administration of saline infusions.
Individuals with anorexia nervosa (AN) are afraid to eat. Moreover, anxiety is a prominent
      symptom in AN, with anxiety disorders frequently preceding and/or co-occurring with the
      illness, and with an increased prevalence of anxiety disorders in first-degree family
      members. Pre-meal anxiety poses a frequent challenge in treatment settings which require
      adherence to strict meal plans, particularly since it is associated with lower caloric
      intake. While problematic under current treatment settings, this illness characteristic also
      provides a potentially important therapeutic target. Unfortunately, straightforward pre-meal
      treatment with typically effective anxiolytic medicines such as alprazolam are ineffective in
      individuals with AN, nor do they increase caloric intake. By contrast, cognitive behavioral
      therapies for anorexia nervosa utilizing exposure therapy, the most effective psychological
      intervention for anxiety and anxiety disorders, can promote food intake and increase weight
      in AN. However, such treatments are slow and have less than ideal response rates, suggesting
      that they could benefit from further optimization. Exposure therapy involves helping patients
      to voluntarily engage in repeated and sometimes prolonged confrontation with the stimulus
      that disproportionately provokes the individual's fear. The aim of this practice is to
      facilitate the development of tolerance or a reduction of the anxiety/fear response that has
      become conditionally associated with the relevant stimulus, thereby demonstrating to patients
      that they can learn to manage effectively in the face of anxiety. In the case of anorexia
      nervosa, the repeated presentation of food and food cues (mental imagery, pictures, smells)
      elicits distress and facilitates the subsequent development of tolerance of these symptoms.
      Unfortunately, the effect size of this intervention in AN is relatively small. Here, the
      researchers investigate whether the use of an acute pharmacological intervention in the
      context of aversive learning to enhance exposure training can reduce anxiety associated with
      eating in individuals with anorexia nervosa.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Double (Participant, Investigator)
measure: Anxiety
time frame: Immediately after drug/placebo infusion
description: Visual analogue self report rating scale
measure: Sensation intensity
time frame: Immediately after drug/placebo infusion
description: Heartbeat and breathing sensation intensity via self report rating scale
measure: Anxiety sensitivity index
time frame: Immediately after drug/placebo infusion
description: Self report rating scale
measure: Positive and Negative Affect
time frame: Immediately after drug/placebo infusion
description: Self report rating scale
measure: Inventory of Depression and Anxiety
time frame: Immediately after drug/placebo infusion
description: Self report rating scale
measure: Multidimensional Assessment of Interoceptive Awareness
time frame: Immediately after drug/placebo infusion
description: Self report rating scale
arm group label: Anorexia nervosa-study drug
arm group type: Experimental
description: Drug: Isoproterenol Intravenous infusions of isoproterenol, delivered in a randomized double blinded order, in each participant. The isoproterenol dose will range from 0.1 micrograms to 4.0 micrograms and exposure during each visit will not exceed 25.0 micrograms. Participants will rate the experience of heartbeat and breathing sensations as well as anxiety induced by the infusion.
Other Names: Isuprel
arm group label: Anorexia nervosa-placebo
arm group type: Placebo Comparator
description: Drug: Normal Saline Intravenous infusions of normal saline, delivered in a randomized double blinded order, in each participant. Participants will rate the experience of heartbeat and breathing sensations as well as anxiety induced by the infusion.
Other Names:
Saline
intervention type: Drug
intervention name: Isoproterenol
description: The goal of this experiment is to use isoproterenol in the context of inhibitory fear learning to reduce eating-related anxiety in AN, and to explore whether these changes are related to interoceptive awareness and autonomic reactivity.
arm group label: Anorexia nervosa-study drug
other name: Isuprel
intervention type: Other
intervention name: placebo
description: placebo
arm group label: Anorexia nervosa-placebo
other name: Normal Saline
criteria: 
gender: All
minimum age: 18 Years
maximum age: 40 Years
healthy volunteers: No
last name: Sahib S Khalsa, MD, PhD
role: Principal Investigator
affiliation: Laureate Institute for Brain Research
facility: 
country: United States
responsible party type: Sponsor
mesh term: Anorexia
mesh term: Anorexia Nervosa
mesh term: Isoproterenol
sharing ipd: No