<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/NCT03810924</url>
  </required_header>
  <id_info>
    <org_study_id>TRR265 A03</org_study_id>
    <nct_id>NCT03810924</nct_id>
  </id_info>
  <brief_title>Stress-related Predictor Profiles in Human Addiction</brief_title>
  <official_title>Stress-related Predictor Profiles for Craving and Relapse in Human Addiction</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Central Institute of Mental Health, Mannheim</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Project Group for Automation in Medicine and Biotechnology PAMB, Mannheim</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Central Institute of Mental Health, Mannheim</source>
  <oversight_info>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Long-term aim is the definition of a setup of mobile sensors and their integration in a&#xD;
      mobile infrastructure that allows the prediction of stress related alcohol intake in an&#xD;
      ambulatory setting. Here, we aim to identify stress- and alcohol cue-related physiological&#xD;
      markers in a lab experiment to assess interactions between acute psychological vs. physical&#xD;
      stress exposure and alcohol cue-exposure regarding their effects on measures relevant for the&#xD;
      development and maintenance of Alcohol Use Disorder (AUD). Further, we aim to identify neural&#xD;
      correlates in brain circuits of motivational, cognitive, and affective processing. In&#xD;
      addition to applying established stress-related markers, we will integrate innovative&#xD;
      sensor-based measures.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      In patients with Alcohol Use Disorder (AUD) stress exposure is known to affect craving,&#xD;
      cue-reactivity and relapse risk. Here, we aim to identify stress- and alcohol cue-related&#xD;
      physiological markers in a lab experiment to assess interactions between acute psychological&#xD;
      vs. physical stress exposure and alcohol cue-exposure regarding their effects on (1) alcohol&#xD;
      craving and related markers (attentional bias to alcohol-cues, implicit association task,&#xD;
      neural cue-reactivity), (2) their predictive capacity for future alcohol intake, (3) the&#xD;
      identification their neural correlates in brain circuits of motivational, cognitive, and&#xD;
      affective processing. In addition to applying established stress-related markers (cortisol in&#xD;
      saliva, heart-rate variability, systolic blood pressure and electrodermal activity), (4) we&#xD;
      will integrate portable sensors (wearables) to allow a future integration in ambulatory&#xD;
      assessments and to test innovative measures currently under investigation (e.g. voice stress&#xD;
      analysis) to identify whether these additional parameters increase the predictive&#xD;
      significance. Our long-term aim is the definition of a setup of mobile sensors and their&#xD;
      integration in a mobile infrastructure that allows the prediction of stress related alcohol&#xD;
      intake in an ambulatory setting.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">July 1, 2019</start_date>
  <completion_date type="Actual">July 8, 2023</completion_date>
  <primary_completion_date type="Actual">September 30, 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>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>change in heart rate</measure>
    <time_frame>at examination day: continuous measurement throughout the whole experiment (except during MRI scanning); duration around 2 hours; starting 1 hour 50 minutes after arrival of the proband</time_frame>
    <description>heart rate acquired with ear clip (continuous time series)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>change in heart rate variability</measure>
    <time_frame>at examination day: continuous measurement throughout the whole experiment (except during MRI scanning); duration around 2 hour; starting 1 hour 50 minutes after arrival of the proband</time_frame>
    <description>heart rate variability acquired with ear clip (continuous time series)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>change in blood pressure (systolic and diastolic)</measure>
    <time_frame>at examination day: 6 time points measured throughout the whole experiment (except during MRI scanning); at hours:minutes 2:20, 2:50, 3:20, 3:50, 4:50, 5:05 after arrival of the proband</time_frame>
    <description>acquired with pressure sleeve</description>
  </primary_outcome>
  <primary_outcome>
    <measure>change in electrodermal activity</measure>
    <time_frame>at examination day: continuous measurement throughout the whole experiment (except during MRI scanning); duration around 2 hour; starting 1h 50min after arrival of the proband</time_frame>
    <description>time series acquired with body sensor</description>
  </primary_outcome>
  <primary_outcome>
    <measure>neural alcohol-related cue-reactivity</measure>
    <time_frame>at examination day: measured directly after the behavioral tasks at the end of the lab experiment</time_frame>
    <description>% signal change, measured with fMRI; paradigm Vollstädt-Klein et al. 2010; [% signal change is not a change over time; it is measured during one experimental session]</description>
  </primary_outcome>
  <primary_outcome>
    <measure>neural inhibition processing</measure>
    <time_frame>at examination day: measured directly after the behavioral tasks at the end of the lab experiment</time_frame>
    <description>% signal change, measured with fMRI; stop-signal reaction time task (Fauth-Buhler et al. 2012) [% signal change is not a change over time; it is measured during one experimental session]</description>
  </primary_outcome>
  <primary_outcome>
    <measure>neural emotion processing</measure>
    <time_frame>at examination day: measured directly after the behavioral tasks at the end of the lab experiment</time_frame>
    <description>% signal change, measured with fMRI; faces task (Hariri et al. 2002) [% signal change is not a change over time; it is measured during one experimental session]</description>
  </primary_outcome>
  <primary_outcome>
    <measure>resting state activity</measure>
    <time_frame>at examination day: measured directly after the behavioral tasks at the end of the lab experiment</time_frame>
    <description>resting state connectivity measured with fMRI</description>
  </primary_outcome>
  <primary_outcome>
    <measure>fMRI</measure>
    <time_frame>at examination day: measured directly after the behavioral tasks at the end of the lab experiment</time_frame>
    <description>neural alcohol-related cue-reactivity, stop-signal reaction time task, emotion processing and resting state fMRI</description>
  </primary_outcome>
  <primary_outcome>
    <measure>attentional bias to alcohol cues</measure>
    <time_frame>at examination day: measured directly after the stress task / newspaper reading; before &quot;implicit alcohol association&quot; and MRI session</time_frame>
    <description>measured with reaction time differences (in milliseconds) using the dotprobe-task (Vollstädt-Klein et al. 2009) [reaction time differences is not a change over time; it is measured during one experimental session]</description>
  </primary_outcome>
  <primary_outcome>
    <measure>implicit alcohol association</measure>
    <time_frame>at examination day: measured after the stress task / newspaper reading, directly after the &quot;attentional bias to alcohol cues&quot; ; before MRI session</time_frame>
    <description>measured with reaction time differences (in milliseconds) using the implicit association task (Wiers et al. 2016) [reaction time differences is not a change over time; it is measured during one experimental session]</description>
  </primary_outcome>
  <primary_outcome>
    <measure>change in level of cortisol</measure>
    <time_frame>at examination day: 6 time points measured throughout the whole experiment (except during MRI scanning); at hours:minutes 2:20, 2:50, 3:20, 3:50, 4:50, 5:05 after arrival of the proband</time_frame>
    <description>cortisol measured in saliva as a stress marker</description>
  </primary_outcome>
  <primary_outcome>
    <measure>change in voice stress pattern</measure>
    <time_frame>at examination day: 6 time points measured throughout the whole experiment (except during MRI scanning); at hours:minutes 2:20, 2:50, 3:20, 3:50, 4:50, 5:05 after arrival of the proband</time_frame>
    <description>audio file of participants' voice for voice stress pattern analysis will be recorded. From this a multivariate measure (i.e. multivariate vector) will be acquired (including frequency, loudness etc.)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>change in alcohol urges</measure>
    <time_frame>at examination day: 6 time points measured throughout the whole experiment (except during MRI scanning); at hours:minutes 2:20, 2:50, 3:20, 3:50, 4:50, 5:05 after arrival of the proband</time_frame>
    <description>self-report questionnaire: &quot;Alcohol Urge Questionnaire (AUQ)&quot;; Bohn et al. 1995</description>
  </primary_outcome>
  <primary_outcome>
    <measure>change in alcohol craving</measure>
    <time_frame>at examination day: 6 time points measured throughout the whole experiment (except during MRI scanning); at hours:minutes 2:20, 2:50, 3:20, 3:50, 4:50, 5:05 after arrival of the proband</time_frame>
    <description>self-report &quot;How strong is your craving for alcohol?&quot;: reported on a visual analogue scale ranging from 0 to 100</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>alcohol consumption</measure>
    <time_frame>12 months follow-up</time_frame>
    <description>self-report using the instrument Form90 (Scheurich et al. 2005)</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">121</enrollment>
  <condition>Alcohol Use Disorder</condition>
  <condition>Stress Reaction</condition>
  <condition>Social Stress</condition>
  <condition>Craving</condition>
  <condition>Relapse</condition>
  <condition>Addiction</condition>
  <condition>Risk Behavior</condition>
  <arm_group>
    <arm_group_label>Control</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Participants reads newspaper before Barlab-Exposure</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Experimental 1 (Distress)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants undergo the Trier Social Stress Test before Barlab-Exposure</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Experimental 2 (Eustress)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants ride an ergometer before Barlab-Exposure</description>
  </arm_group>
  <intervention>
    <intervention_type>Behavioral</intervention_type>
    <intervention_name>Trier Social Stress Test</intervention_name>
    <description>Test to induce high levels of acute social stress, including actors and a faked exam situation</description>
    <arm_group_label>Experimental 1 (Distress)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Behavioral</intervention_type>
    <intervention_name>Ergometer</intervention_name>
    <description>Riding ergometer</description>
    <arm_group_label>Experimental 2 (Eustress)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Behavioral</intervention_type>
    <intervention_name>Barlab-Exposure</intervention_name>
    <description>Participants are exposed to a bar situation with different sorts of alcohol available. They sniff at water and at one alcoholic drink.</description>
    <arm_group_label>Control</arm_group_label>
    <arm_group_label>Experimental 1 (Distress)</arm_group_label>
    <arm_group_label>Experimental 2 (Eustress)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Behavioral</intervention_type>
    <intervention_name>Reading Newspaper</intervention_name>
    <description>Participants read newspaper</description>
    <arm_group_label>Control</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Alcohol-use disorder according to 2 DSM-V criteria not requiring detoxification: AUD&#xD;
             subjects with mild AUD will fulfill at least 2 and not more than 5 diagnostic&#xD;
             criteria; a second group of AUD subjects will fulfill 4-5 criteria for moderate AUD&#xD;
&#xD;
          -  sufficient ability to communicate with the investigators, to answer questions in oral&#xD;
             and written form&#xD;
&#xD;
          -  fully informed consent&#xD;
&#xD;
          -  written informed consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  withdrawal of the declaration of consent&#xD;
&#xD;
          -  Pregnancy&#xD;
&#xD;
          -  Using hormonal contraceptives&#xD;
&#xD;
          -  Perimenopausal/ postmenopausal&#xD;
&#xD;
          -  positive urin drug screening (cannabis, amphetamine, opiates, benzodiazepines,&#xD;
             cocaine)&#xD;
&#xD;
          -  Lifetime history of DSM-5 bipolar disorder, schizophrenia or schizophrenia spectrum&#xD;
             disorder, or substance dependence other than alcohol or nicotine or cannabis&#xD;
             dependence.&#xD;
&#xD;
          -  Current threshold DSM-5 diagnosis of major depressive disorder, or presence of&#xD;
             suicidal intention&#xD;
&#xD;
          -  History of severe head trauma or other severe central nervous system disorder (e.g.,&#xD;
             dementia, Parkinson's disease, multiple sclerosis)&#xD;
&#xD;
          -  Current use of medications or drugs known to interact with the CNS within at least&#xD;
             four half-lives post last intake&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Falk Kiefer, Prof.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Central Institute of Mental Health, Mannheim</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Klinik für Abhängiges Verhalten, Zentralinstitut für Seelische Gesundheit</name>
      <address>
        <city>Mannheim</city>
        <state>Baden-Württemberg</state>
        <zip>68159</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Germany</country>
  </location_countries>
  <verification_date>September 2023</verification_date>
  <study_first_submitted>November 26, 2018</study_first_submitted>
  <study_first_submitted_qc>January 16, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 22, 2019</study_first_posted>
  <last_update_submitted>September 14, 2023</last_update_submitted>
  <last_update_submitted_qc>September 14, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">September 15, 2023</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>Recurrence</mesh_term>
    <mesh_term>Alcoholism</mesh_term>
    <mesh_term>Fractures, Stress</mesh_term>
    <mesh_term>Behavior, Addictive</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/NCT03810924
org study id: TRR265 A03
nct id: NCT03810924
lead sponsor: 
collaborator: 
is fda regulated drug: No
is fda regulated device: No
Long-term aim is the definition of a setup of mobile sensors and their integration in a
      mobile infrastructure that allows the prediction of stress related alcohol intake in an
      ambulatory setting. Here, we aim to identify stress- and alcohol cue-related physiological
      markers in a lab experiment to assess interactions between acute psychological vs. physical
      stress exposure and alcohol cue-exposure regarding their effects on measures relevant for the
      development and maintenance of Alcohol Use Disorder (AUD). Further, we aim to identify neural
      correlates in brain circuits of motivational, cognitive, and affective processing. In
      addition to applying established stress-related markers, we will integrate innovative
      sensor-based measures.
In patients with Alcohol Use Disorder (AUD) stress exposure is known to affect craving,
      cue-reactivity and relapse risk. Here, we aim to identify stress- and alcohol cue-related
      physiological markers in a lab experiment to assess interactions between acute psychological
      vs. physical stress exposure and alcohol cue-exposure regarding their effects on (1) alcohol
      craving and related markers (attentional bias to alcohol-cues, implicit association task,
      neural cue-reactivity), (2) their predictive capacity for future alcohol intake, (3) the
      identification their neural correlates in brain circuits of motivational, cognitive, and
      affective processing. In addition to applying established stress-related markers (cortisol in
      saliva, heart-rate variability, systolic blood pressure and electrodermal activity), (4) we
      will integrate portable sensors (wearables) to allow a future integration in ambulatory
      assessments and to test innovative measures currently under investigation (e.g. voice stress
      analysis) to identify whether these additional parameters increase the predictive
      significance. Our long-term aim is the definition of a setup of mobile sensors and their
      integration in a mobile infrastructure that allows the prediction of stress related alcohol
      intake in an ambulatory setting.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: change in heart rate
time frame: at examination day: continuous measurement throughout the whole experiment (except during MRI scanning); duration around 2 hours; starting 1 hour 50 minutes after arrival of the proband
description: heart rate acquired with ear clip (continuous time series)
measure: change in heart rate variability
time frame: at examination day: continuous measurement throughout the whole experiment (except during MRI scanning); duration around 2 hour; starting 1 hour 50 minutes after arrival of the proband
description: heart rate variability acquired with ear clip (continuous time series)
measure: change in blood pressure (systolic and diastolic)
time frame: at examination day: 6 time points measured throughout the whole experiment (except during MRI scanning); at hours:minutes 2:20, 2:50, 3:20, 3:50, 4:50, 5:05 after arrival of the proband
description: acquired with pressure sleeve
measure: change in electrodermal activity
time frame: at examination day: continuous measurement throughout the whole experiment (except during MRI scanning); duration around 2 hour; starting 1h 50min after arrival of the proband
description: time series acquired with body sensor
measure: neural alcohol-related cue-reactivity
time frame: at examination day: measured directly after the behavioral tasks at the end of the lab experiment
description: % signal change, measured with fMRI; paradigm Vollstädt-Klein et al. 2010; [% signal change is not a change over time; it is measured during one experimental session]
measure: neural inhibition processing
time frame: at examination day: measured directly after the behavioral tasks at the end of the lab experiment
description: % signal change, measured with fMRI; stop-signal reaction time task (Fauth-Buhler et al. 2012) [% signal change is not a change over time; it is measured during one experimental session]
measure: neural emotion processing
time frame: at examination day: measured directly after the behavioral tasks at the end of the lab experiment
description: % signal change, measured with fMRI; faces task (Hariri et al. 2002) [% signal change is not a change over time; it is measured during one experimental session]
measure: resting state activity
time frame: at examination day: measured directly after the behavioral tasks at the end of the lab experiment
description: resting state connectivity measured with fMRI
measure: fMRI
time frame: at examination day: measured directly after the behavioral tasks at the end of the lab experiment
description: neural alcohol-related cue-reactivity, stop-signal reaction time task, emotion processing and resting state fMRI
measure: attentional bias to alcohol cues
time frame: at examination day: measured directly after the stress task / newspaper reading; before "implicit alcohol association" and MRI session
description: measured with reaction time differences (in milliseconds) using the dotprobe-task (Vollstädt-Klein et al. 2009) [reaction time differences is not a change over time; it is measured during one experimental session]
measure: implicit alcohol association
time frame: at examination day: measured after the stress task / newspaper reading, directly after the "attentional bias to alcohol cues" ; before MRI session
description: measured with reaction time differences (in milliseconds) using the implicit association task (Wiers et al. 2016) [reaction time differences is not a change over time; it is measured during one experimental session]
measure: change in level of cortisol
time frame: at examination day: 6 time points measured throughout the whole experiment (except during MRI scanning); at hours:minutes 2:20, 2:50, 3:20, 3:50, 4:50, 5:05 after arrival of the proband
description: cortisol measured in saliva as a stress marker
measure: change in voice stress pattern
time frame: at examination day: 6 time points measured throughout the whole experiment (except during MRI scanning); at hours:minutes 2:20, 2:50, 3:20, 3:50, 4:50, 5:05 after arrival of the proband
description: audio file of participants' voice for voice stress pattern analysis will be recorded. From this a multivariate measure (i.e. multivariate vector) will be acquired (including frequency, loudness etc.)
measure: change in alcohol urges
time frame: at examination day: 6 time points measured throughout the whole experiment (except during MRI scanning); at hours:minutes 2:20, 2:50, 3:20, 3:50, 4:50, 5:05 after arrival of the proband
description: self-report questionnaire: "Alcohol Urge Questionnaire (AUQ)"; Bohn et al. 1995
measure: change in alcohol craving
time frame: at examination day: 6 time points measured throughout the whole experiment (except during MRI scanning); at hours:minutes 2:20, 2:50, 3:20, 3:50, 4:50, 5:05 after arrival of the proband
description: self-report "How strong is your craving for alcohol?": reported on a visual analogue scale ranging from 0 to 100
measure: alcohol consumption
time frame: 12 months follow-up
description: self-report using the instrument Form90 (Scheurich et al. 2005)
arm group label: Control
arm group type: Active Comparator
description: Participants reads newspaper before Barlab-Exposure
arm group label: Experimental 1 (Distress)
arm group type: Experimental
description: Participants undergo the Trier Social Stress Test before Barlab-Exposure
arm group label: Experimental 2 (Eustress)
arm group type: Experimental
description: Participants ride an ergometer before Barlab-Exposure
intervention type: Behavioral
intervention name: Trier Social Stress Test
description: Test to induce high levels of acute social stress, including actors and a faked exam situation
arm group label: Experimental 1 (Distress)
intervention type: Behavioral
intervention name: Ergometer
description: Riding ergometer
arm group label: Experimental 2 (Eustress)
intervention type: Behavioral
intervention name: Barlab-Exposure
description: Participants are exposed to a bar situation with different sorts of alcohol available. They sniff at water and at one alcoholic drink.
arm group label: Control
arm group label: Experimental 1 (Distress)
arm group label: Experimental 2 (Eustress)
intervention type: Behavioral
intervention name: Reading Newspaper
description: Participants read newspaper
arm group label: Control
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: No
last name: Falk Kiefer, Prof.
role: Principal Investigator
affiliation: Central Institute of Mental Health, Mannheim
facility: 
country: Germany
responsible party type: Sponsor
mesh term: Recurrence
mesh term: Alcoholism
mesh term: Fractures, Stress
mesh term: Behavior, Addictive
sharing ipd: No