<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/NCT03758053</url>
  </required_header>
  <id_info>
    <org_study_id>GRK2350-B5</org_study_id>
    <nct_id>NCT03758053</nct_id>
  </id_info>
  <brief_title>Adverse Childhood Experiences in Substance-related Disorders</brief_title>
  <official_title>Stress Sensitivity, Emotion Processing and Cue-reactivity: the Influence of Adverse Childhood Experiences in Substance-related Disorders</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Central Institute of Mental Health, Mannheim</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>German Research Foundation</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>
      Aversive childhood experiences (ACE) and their relation to the development of an alcohol use&#xD;
      disorder will be measured with fMRI.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The aim of this study is to examine the impact of ACE on stress sensitivity, cue-reactivity&#xD;
      and emotion processing in individuals with AUD. (Neuro-) biological and physiological&#xD;
      mechanisms underlying AUD after ACE will be studied.&#xD;
&#xD;
      Neural correlates of stress-sensitivity, emotion processing and alcohol cue-reactivity will&#xD;
      be assessed using fMRI. Furthermore, blood and saliva samples will be used to assess&#xD;
      biological and physiological mechanisms (e.g. salivary cortisol level or genetic markers of&#xD;
      AUD and possible gene-environment-interactions).&#xD;
&#xD;
      The question whether individuals with AUD and ACE might tend to use alcohol to cope with&#xD;
      stress, negative affect or intrusions (according to the self-medication model) will be&#xD;
      explored. On the other hand, individuals with AUD and low levels of ACE might use alcohol for&#xD;
      its positive effects (according to a positive reinforcement model).&#xD;
&#xD;
      90 individuals (30 HC and 60 individuals with AUD and varying levels of ACE) will be examined&#xD;
      using interviews, questionnaires and fMRI tasks as well as saliva and blood samples. All&#xD;
      ethical votes and informed consents of participants are and will be obtained according to the&#xD;
      declaration of Helsinki.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Active, not recruiting</last_known_status>
  <start_date type="Actual">December 15, 2018</start_date>
  <completion_date type="Anticipated">August 31, 2021</completion_date>
  <primary_completion_date type="Actual">May 27, 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>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>fMRI to assess group differences in task-specific brain activation patterns: Stress-sensitivity</measure>
    <time_frame>fMRI measurement at one day only (day of fMRI experiment)</time_frame>
    <description>Stress-sensitivity: stress task (e.g.mental rotation with and without time pressure) with social component within the MRI scanner to assess neural activation patters during the stress-task</description>
  </primary_outcome>
  <primary_outcome>
    <measure>fMRI to assess group differences in task-specific brain activation patterns: Emotion processing</measure>
    <time_frame>fMRI measurement at one day only (day of fMRI experiment)</time_frame>
    <description>Emotion-processing: emotional face-/form-matching task to assess neural activation patters of emotion processing</description>
  </primary_outcome>
  <primary_outcome>
    <measure>fMRI to assess group differences in task-specific brain activation patterns: Alcohol cue-reactivity</measure>
    <time_frame>fMRI measurement at one day only (day of fMRI experiment)</time_frame>
    <description>Alcohol cue-reactivity: pictures of alcoholic beverages to asses neural alcohol-cue reactivity</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Hormonal stress response using salivary cortisol level</measure>
    <time_frame>Normal awakening response on a subject's regular week-day (0, 0.5, 8 and 14 hours after wake-up)</time_frame>
    <description>Collection of saliva on a subject's regular week-day for the individual's normal cortisol awakening response and circadian rhythm (basal hypothalamic-pituitary-adrenal-function at 0, 0.5, 8 and 14 hours after wake-up).&#xD;
Cortisol awakening reaction, area under the curve and slope will therefore be calculated [nmol/L].</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Hormonal stress response using salivary cortisol level</measure>
    <time_frame>Stress response during the fMRI stress task (day of fMRI experiment, at -45, -22, -10 minutes before and 35, 45, 60, 75 and 90 minutes after onset of stress induction)</time_frame>
    <description>Collection of saliva during the course of the fMRI stress task for task-induced stress effects on salivary cortisol levels (at -45, -22, -10 minutes before and 35, 45, 60, 75 and 90 minutes after onset of stress induction).&#xD;
Cortisol: Area under the curve and slope will therefore be calculated [nmol/L].</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>GWAS and especially glutamatergic, serotonergic single-nucleotide polymorphisms</measure>
    <time_frame>blood sample at one day only (day of fMRI experiment)</time_frame>
    <description>Genomic DNA using 40ml EDTA-blood</description>
  </secondary_outcome>
  <number_of_groups>3</number_of_groups>
  <enrollment type="Actual">70</enrollment>
  <condition>Alcohol Use Disorder</condition>
  <condition>Trauma, Psychological</condition>
  <arm_group>
    <arm_group_label>Individuals with alcohol use disorder + ACE</arm_group_label>
    <description>Individuals with AUD and varying levels of adverse childhood experiences (ACE)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Healthy controls</arm_group_label>
    <description>Healthy individuals without AUD</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Individuals with alcohol use disorder, no ACE</arm_group_label>
    <description>Individuals with AUD and no adverse childhood experiences (ACE)</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>No intervention</intervention_name>
    <description>No intervention</description>
    <arm_group_label>Healthy controls</arm_group_label>
    <arm_group_label>Individuals with alcohol use disorder + ACE</arm_group_label>
    <arm_group_label>Individuals with alcohol use disorder, no ACE</arm_group_label>
    <other_name>observational study</other_name>
  </intervention>
  <biospec_retention>Samples With DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      Saliva (stress hormones) Blood (genotyping)&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        Residents from Mannheim/ Heidelberg who answered an open call to participate in this study&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  male and female&#xD;
&#xD;
          -  age between 18 and 65&#xD;
&#xD;
          -  normal or correctable eyesight&#xD;
&#xD;
          -  Sufficient ability to communicate with the investigators, to answer questions in oral&#xD;
             and written form&#xD;
&#xD;
          -  &quot;Fully Informed Consent&quot;&#xD;
&#xD;
          -  &quot;Written Informed Consent&quot;&#xD;
&#xD;
          -  Healthy individuals (AUDIT Score&lt;=8, alcohol intake &lt; 12g/ less than 5 days (women) &amp;&#xD;
             24g/ less than 5 days (men)&#xD;
&#xD;
          -  Individuals with alcohol use disorder according to DSM-5 or 'heavy drinking' (alcohol&#xD;
             intake &gt; 40g/ more than 5 days (women) &amp; 60g/ more than 5 days (men) with up to 28&#xD;
             days of abstinence AND aversive childhood experiences&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Withdrawal of the declaration of consent&#xD;
&#xD;
          -  Exclusion criteria for an MRI scan (pregnancy, metal implants,...)&#xD;
&#xD;
          -  severe internal, neurological and psychiatric comorbidities&#xD;
&#xD;
          -  Pharmacotherapy with psychoactive substances within the last 14 days (except treatment&#xD;
             with SSRI/SNRIs for at least 28 days)&#xD;
&#xD;
          -  Axis-I disorder according to ICD-10 and DSM 5 (except tobacco and alcohol use&#xD;
             disorder, substance abuse with less than 2(11) criteria according to DSM-5, mild&#xD;
             depressive episode, adaptation disorder and specific phobia within the last 12 months)&#xD;
&#xD;
          -  positive urin drug screening (cannabis, amphetamine, opiates, benzodiazepines,&#xD;
             cocaine)&#xD;
&#xD;
          -  withdrawal symptoms (CIWA-R &gt; 7)&#xD;
&#xD;
          -  intoxication at time of investigation (breathalyzer &gt; 0.3‰)&#xD;
&#xD;
          -  suicidal tendency or potential danger for others&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Sabine Vollstaedt-Klein</last_name>
    <role>Principal Investigator</role>
    <affiliation>CIMH Mannheim</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Klinik für Abhängiges Verhalten, Zentralinstitut für Seelische Gesundheit</name>
      <address>
        <city>Mannheim</city>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Germany</country>
  </location_countries>
  <verification_date>July 2021</verification_date>
  <study_first_submitted>August 20, 2018</study_first_submitted>
  <study_first_submitted_qc>November 28, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">November 29, 2018</study_first_posted>
  <last_update_submitted>July 28, 2021</last_update_submitted>
  <last_update_submitted_qc>July 28, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">July 29, 2021</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>Alcoholism</mesh_term>
    <mesh_term>Substance-Related Disorders</mesh_term>
    <mesh_term>Psychological Trauma</mesh_term>
  </condition_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/NCT03758053
org study id: GRK2350-B5
nct id: NCT03758053
lead sponsor: 
collaborator: 
is fda regulated drug: No
is fda regulated device: No
Aversive childhood experiences (ACE) and their relation to the development of an alcohol use
      disorder will be measured with fMRI.
The aim of this study is to examine the impact of ACE on stress sensitivity, cue-reactivity
      and emotion processing in individuals with AUD. (Neuro-) biological and physiological
      mechanisms underlying AUD after ACE will be studied.

      Neural correlates of stress-sensitivity, emotion processing and alcohol cue-reactivity will
      be assessed using fMRI. Furthermore, blood and saliva samples will be used to assess
      biological and physiological mechanisms (e.g. salivary cortisol level or genetic markers of
      AUD and possible gene-environment-interactions).

      The question whether individuals with AUD and ACE might tend to use alcohol to cope with
      stress, negative affect or intrusions (according to the self-medication model) will be
      explored. On the other hand, individuals with AUD and low levels of ACE might use alcohol for
      its positive effects (according to a positive reinforcement model).

      90 individuals (30 HC and 60 individuals with AUD and varying levels of ACE) will be examined
      using interviews, questionnaires and fMRI tasks as well as saliva and blood samples. All
      ethical votes and informed consents of participants are and will be obtained according to the
      declaration of Helsinki.
observational model: Case-Control
time perspective: Prospective
measure: fMRI to assess group differences in task-specific brain activation patterns: Stress-sensitivity
time frame: fMRI measurement at one day only (day of fMRI experiment)
description: Stress-sensitivity: stress task (e.g.mental rotation with and without time pressure) with social component within the MRI scanner to assess neural activation patters during the stress-task
measure: fMRI to assess group differences in task-specific brain activation patterns: Emotion processing
time frame: fMRI measurement at one day only (day of fMRI experiment)
description: Emotion-processing: emotional face-/form-matching task to assess neural activation patters of emotion processing
measure: fMRI to assess group differences in task-specific brain activation patterns: Alcohol cue-reactivity
time frame: fMRI measurement at one day only (day of fMRI experiment)
description: Alcohol cue-reactivity: pictures of alcoholic beverages to asses neural alcohol-cue reactivity
measure: Hormonal stress response using salivary cortisol level
time frame: Normal awakening response on a subject's regular week-day (0, 0.5, 8 and 14 hours after wake-up)
description: Collection of saliva on a subject's regular week-day for the individual's normal cortisol awakening response and circadian rhythm (basal hypothalamic-pituitary-adrenal-function at 0, 0.5, 8 and 14 hours after wake-up).
Cortisol awakening reaction, area under the curve and slope will therefore be calculated [nmol/L].
measure: Hormonal stress response using salivary cortisol level
time frame: Stress response during the fMRI stress task (day of fMRI experiment, at -45, -22, -10 minutes before and 35, 45, 60, 75 and 90 minutes after onset of stress induction)
description: Collection of saliva during the course of the fMRI stress task for task-induced stress effects on salivary cortisol levels (at -45, -22, -10 minutes before and 35, 45, 60, 75 and 90 minutes after onset of stress induction).
Cortisol: Area under the curve and slope will therefore be calculated [nmol/L].
measure: GWAS and especially glutamatergic, serotonergic single-nucleotide polymorphisms
time frame: blood sample at one day only (day of fMRI experiment)
description: Genomic DNA using 40ml EDTA-blood
arm group label: Individuals with alcohol use disorder + ACE
description: Individuals with AUD and varying levels of adverse childhood experiences (ACE)
arm group label: Healthy controls
description: Healthy individuals without AUD
arm group label: Individuals with alcohol use disorder, no ACE
description: Individuals with AUD and no adverse childhood experiences (ACE)
intervention type: Other
intervention name: No intervention
description: No intervention
arm group label: Healthy controls
arm group label: Individuals with alcohol use disorder + ACE
arm group label: Individuals with alcohol use disorder, no ACE
other name: observational study
Saliva (stress hormones) Blood (genotyping)
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Sabine Vollstaedt-Klein
role: Principal Investigator
affiliation: CIMH Mannheim
facility: 
country: Germany
responsible party type: Sponsor
mesh term: Alcoholism
mesh term: Substance-Related Disorders
mesh term: Psychological Trauma