<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/NCT02196142</url>
  </required_header>
  <id_info>
    <org_study_id>068/14</org_study_id>
    <nct_id>NCT02196142</nct_id>
  </id_info>
  <brief_title>Acute Effects of Cortisol on Alcohol Craving in Alcohol Dependence</brief_title>
  <acronym>CAR-Bern 2013</acronym>
  <official_title>Acute Effects of Cortisol on Alcohol Craving in Alcohol Dependence</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Insel Gruppe AG, University Hospital Bern</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Insel Gruppe AG, University Hospital Bern</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      To investigate the effects of cortisol on alcohol craving and stress reactivity in alcohol&#xD;
      addicted subjects.&#xD;
&#xD;
      Randomized, double-blind, placebo-controlled, cross-over, single administration of study&#xD;
      medication.&#xD;
&#xD;
      Study hypothesis: Cortisol has an inhibiting effect on alcohol craving and stress reactivity&#xD;
      in alcohol dependent subjects.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Background&#xD;
&#xD;
      Alcohol dependence is a chronically and relapsing disorder with major impact on the persons&#xD;
      psychological, physiological and social functioning. There is extensive evidence from animal&#xD;
      and human studies pointing out the important role of addiction memory in the development and&#xD;
      maintenance of the disorder.&#xD;
&#xD;
      Cognitive behavioural therapy (CBT) has proven its high effectiveness in the treatment for&#xD;
      addictive disorders. A core element of CBT are exposure techniques that are comparable to&#xD;
      extinction and habituation learning. The repeated exposure to alcohol related cues in the&#xD;
      absence of alcohol ingestion will lead to extinction of conditioned responses, thus reducing&#xD;
      the probability of relapse to alcohol taking behaviour.&#xD;
&#xD;
      Studies have shown that glucocorticoids impair memory retrieval in healthy subjects. In fact,&#xD;
      the investigators could show that cortisol has a fear reducing effect in patients with&#xD;
      post-traumatic stress disorder and in phobic patients, resulting particularly in reduced&#xD;
      symptoms of anxiety and in reduced stress reactivity. Interestingly enough, pharmacologically&#xD;
      induced high levels of glucocorticoids lowered the subjective feeling of anxiety and stress&#xD;
      in situations activating per se the HPA-axis. Further it has been shown that the combined&#xD;
      therapy of glucocorticoid administration and exposition based psychotherapy leads to better&#xD;
      therapy outcome in patients with specific phobias.&#xD;
&#xD;
      Objective&#xD;
&#xD;
      The goal of this study is to examine the acute effects of glucocorticoids administration on&#xD;
      alcohol craving and stress reactivity of abstinent alcohol dependent patients. On the basis&#xD;
      of clinical research in anxiety disorders, the investigators expect that a pharmacologically&#xD;
      increased cortisol level may impair the retrieval of addiction memory, which is indicated by&#xD;
      less craving during the alcohol exposition, while exposition therapy enhances consolidation&#xD;
      of corrective experiences. Similar to the research in anxiety patients, the investigators aim&#xD;
      to examine whether cortisol administration could help improve the effects of exposition&#xD;
      therapy in patients with alcohol dependence. The purpose is to decrease therapy duration&#xD;
      through cortisol administration in addition to already well proven therapies and make the&#xD;
      therapy more efficient as well as a factor in reducing healthcare costs.&#xD;
&#xD;
      Methods&#xD;
&#xD;
      Patients undergo two identical experimental sessions between the 6th and 8th week (one week&#xD;
      in between) of their 12-week inpatient treatment program for alcohol dependence. The&#xD;
      experiment takes place in the experimental rooms of the clinic Südhang between 1 and 6 pm.&#xD;
      One hour before the confrontation with alcohol associated stimuli patients receive either&#xD;
      20mg of hydrocortisone or placebo (oral administration). The experiment consists of a&#xD;
      computer based picture task (alcoholic and neutral pictures) and an in-vivo exposure task.&#xD;
      Psychological (craving, stress, arousal) and physiological (heart rate, saliva cortisol)&#xD;
      parameters are repeatedly measured over the course of the experiment.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>November 2014</start_date>
  <completion_date type="Actual">June 2015</completion_date>
  <primary_completion_date type="Actual">June 2015</primary_completion_date>
  <phase>Phase 3</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Crossover Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change from baseline in alcohol craving score</measure>
    <time_frame>During and after presentation of drug stimuli, expected to be after 10 minutes</time_frame>
    <description>Measured by Alcohol Urge Questionnaire &amp; Visual Analogue Scale</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change from baseline in State-Trait-Anger Expression Inventory STAXI</measure>
    <time_frame>After presentation of drug stimuli, expected to be after 20 minutes</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from baseline in heart rate variability</measure>
    <time_frame>During and after presentation of drug stimuli, expected to be after 10 minutes</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Saliva Cortisol Level</measure>
    <time_frame>After presentation of drug stimuli, expected to be after 90 minutes</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">48</enrollment>
  <condition>Alcohol Craving</condition>
  <condition>Psychological Stress</condition>
  <condition>Physiological Stress</condition>
  <arm_group>
    <arm_group_label>Cortisol first, Placebo second</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Drug: Cortisol 20mg, Drug: Mannitol (used as placebo)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo first, Cortisol second</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Drug: Cortisol 20mg, Drug: Mannitol (used as placebo)</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Cortisol 20mg</intervention_name>
    <description>Drug: Cortisol 20mg</description>
    <arm_group_label>Cortisol first, Placebo second</arm_group_label>
    <arm_group_label>Placebo first, Cortisol second</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo Mannitol</intervention_name>
    <description>Drug: Placebo Mannitol</description>
    <arm_group_label>Cortisol first, Placebo second</arm_group_label>
    <arm_group_label>Placebo first, Cortisol second</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age ≥ 18&#xD;
&#xD;
          -  Abstinent alcoholics in the 12-week in-patient program of the Clinic Südhang&#xD;
&#xD;
          -  Abstained from alcohol for at least 6 weeks&#xD;
&#xD;
          -  Voluntarily signed informed consent&#xD;
&#xD;
        Exclusion Criteria&#xD;
&#xD;
          -  Co-morbid psychiatric disturbances (such as major depression, bipolar disorder,&#xD;
             schizophrenia)&#xD;
&#xD;
          -  Current medical conditions excluding participation (such as acute infectious disease)&#xD;
&#xD;
          -  Recent history of systemic or topic glucocorticoid therapy&#xD;
&#xD;
          -  Known hypersensitivity to the IMP under investigation (cortisol)&#xD;
&#xD;
          -  Pregnancy, breast-feeding&#xD;
&#xD;
          -  Inability to read and understand the participant's information&#xD;
&#xD;
          -  Positive alcohol test according to breathalyser&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Leila Soravia, Dr. phil.</last_name>
    <role>Study Director</role>
    <affiliation>University Hospital of Psychiatry Bern</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Peter Allemann, Dr. med.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Clinic Südhang</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Dominique de Quervain, Prof. Dr.</last_name>
    <role>Study Chair</role>
    <affiliation>University Hospital, Basel, Switzerland</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Klinik Südhang</name>
      <address>
        <city>Kirchlindach</city>
        <state>Bern</state>
        <zip>CH-3038</zip>
        <country>Switzerland</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Switzerland</country>
  </location_countries>
  <verification_date>June 2015</verification_date>
  <study_first_submitted>July 17, 2014</study_first_submitted>
  <study_first_submitted_qc>July 18, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">July 21, 2014</study_first_posted>
  <last_update_submitted>June 23, 2015</last_update_submitted>
  <last_update_submitted_qc>June 23, 2015</last_update_submitted_qc>
  <last_update_posted type="Estimate">June 24, 2015</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Cortisol</keyword>
  <keyword>Alcohol Craving</keyword>
  <keyword>Alcohol Dependence</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Alcoholism</mesh_term>
    <mesh_term>Stress, Psychological</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Hydrocortisone</mesh_term>
    <mesh_term>Mannitol</mesh_term>
  </intervention_browse>
  <!-- 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/NCT02196142
org study id: 068/14
nct id: NCT02196142
lead sponsor: 
has dmc: No
To investigate the effects of cortisol on alcohol craving and stress reactivity in alcohol
      addicted subjects.

      Randomized, double-blind, placebo-controlled, cross-over, single administration of study
      medication.

      Study hypothesis: Cortisol has an inhibiting effect on alcohol craving and stress reactivity
      in alcohol dependent subjects.
Background

      Alcohol dependence is a chronically and relapsing disorder with major impact on the persons
      psychological, physiological and social functioning. There is extensive evidence from animal
      and human studies pointing out the important role of addiction memory in the development and
      maintenance of the disorder.

      Cognitive behavioural therapy (CBT) has proven its high effectiveness in the treatment for
      addictive disorders. A core element of CBT are exposure techniques that are comparable to
      extinction and habituation learning. The repeated exposure to alcohol related cues in the
      absence of alcohol ingestion will lead to extinction of conditioned responses, thus reducing
      the probability of relapse to alcohol taking behaviour.

      Studies have shown that glucocorticoids impair memory retrieval in healthy subjects. In fact,
      the investigators could show that cortisol has a fear reducing effect in patients with
      post-traumatic stress disorder and in phobic patients, resulting particularly in reduced
      symptoms of anxiety and in reduced stress reactivity. Interestingly enough, pharmacologically
      induced high levels of glucocorticoids lowered the subjective feeling of anxiety and stress
      in situations activating per se the HPA-axis. Further it has been shown that the combined
      therapy of glucocorticoid administration and exposition based psychotherapy leads to better
      therapy outcome in patients with specific phobias.

      Objective

      The goal of this study is to examine the acute effects of glucocorticoids administration on
      alcohol craving and stress reactivity of abstinent alcohol dependent patients. On the basis
      of clinical research in anxiety disorders, the investigators expect that a pharmacologically
      increased cortisol level may impair the retrieval of addiction memory, which is indicated by
      less craving during the alcohol exposition, while exposition therapy enhances consolidation
      of corrective experiences. Similar to the research in anxiety patients, the investigators aim
      to examine whether cortisol administration could help improve the effects of exposition
      therapy in patients with alcohol dependence. The purpose is to decrease therapy duration
      through cortisol administration in addition to already well proven therapies and make the
      therapy more efficient as well as a factor in reducing healthcare costs.

      Methods

      Patients undergo two identical experimental sessions between the 6th and 8th week (one week
      in between) of their 12-week inpatient treatment program for alcohol dependence. The
      experiment takes place in the experimental rooms of the clinic Südhang between 1 and 6 pm.
      One hour before the confrontation with alcohol associated stimuli patients receive either
      20mg of hydrocortisone or placebo (oral administration). The experiment consists of a
      computer based picture task (alcoholic and neutral pictures) and an in-vivo exposure task.
      Psychological (craving, stress, arousal) and physiological (heart rate, saliva cortisol)
      parameters are repeatedly measured over the course of the experiment.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Treatment
masking: Double (Participant, Investigator)
measure: Change from baseline in alcohol craving score
time frame: During and after presentation of drug stimuli, expected to be after 10 minutes
description: Measured by Alcohol Urge Questionnaire & Visual Analogue Scale
measure: Change from baseline in State-Trait-Anger Expression Inventory STAXI
time frame: After presentation of drug stimuli, expected to be after 20 minutes
measure: Change from baseline in heart rate variability
time frame: During and after presentation of drug stimuli, expected to be after 10 minutes
measure: Saliva Cortisol Level
time frame: After presentation of drug stimuli, expected to be after 90 minutes
arm group label: Cortisol first, Placebo second
arm group type: Active Comparator
description: Drug: Cortisol 20mg, Drug: Mannitol (used as placebo)
arm group label: Placebo first, Cortisol second
arm group type: Active Comparator
description: Drug: Cortisol 20mg, Drug: Mannitol (used as placebo)
intervention type: Drug
intervention name: Cortisol 20mg
description: Drug: Cortisol 20mg
arm group label: Cortisol first, Placebo second
arm group label: Placebo first, Cortisol second
intervention type: Drug
intervention name: Placebo Mannitol
description: Drug: Placebo Mannitol
arm group label: Cortisol first, Placebo second
arm group label: Placebo first, Cortisol second
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Leila Soravia, Dr. phil.
role: Study Director
affiliation: University Hospital of Psychiatry Bern
last name: Peter Allemann, Dr. med.
role: Principal Investigator
affiliation: Clinic Südhang
last name: Dominique de Quervain, Prof. Dr.
role: Study Chair
affiliation: University Hospital, Basel, Switzerland
facility: 
country: Switzerland
responsible party type: Sponsor
mesh term: Alcoholism
mesh term: Stress, Psychological
mesh term: Hydrocortisone
mesh term: Mannitol