<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/NCT03764969</url>
  </required_header>
  <id_info>
    <org_study_id>TRR265 C01</org_study_id>
    <nct_id>NCT03764969</nct_id>
  </id_info>
  <brief_title>Modification of Goal-directed and Habitual Behavior in Addiction</brief_title>
  <official_title>Modification of the Imbalance Between Goal-directed and Habitual Behavior in Human Addiction</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Central Institute of Mental Health, Mannheim</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </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>
      This study aims to examine the modification of the hypothesized imbalance between&#xD;
      goal-directed and habitual behavior and its neural correlates in smokers. Two interventions&#xD;
      will be used as add-on trainings to a smoking cessation program.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      In this study, the investigators aim to assess the imbalance between goal-directed and&#xD;
      habitual behavior, its neural basis and how it can be differentially modified in&#xD;
      treatment-seeking smokers, using two training interventions. The first intervention is&#xD;
      cognitive remediation treatment (CRT), also known as cognitive enhancement therapy, focusing&#xD;
      on improving inhibitory control and executive functions. The second intervention, a&#xD;
      computer-based habit-modifying training focusing on implicit drug seeking (&quot;implicit&#xD;
      computer-based habit-modifying training&quot;, ICHT) uses a conditioning approach through implicit&#xD;
      priming and contextual modulation. Indicators of the imbalance will be examined with respect&#xD;
      to reward devaluation, cue reactivity and a pavlovian instrumental transfer (PIT) paradigm.&#xD;
      The investigators hypothesize that both interventions change the balance between&#xD;
      goal-directed and habitual behavior but by different mechanisms. Whereas CRT should directly&#xD;
      increase cognitive control, in contrast, ICHT should affect the early processing and the&#xD;
      emotional valence of smoking and smoking cues.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">January 7, 2020</start_date>
  <completion_date type="Anticipated">June 30, 2023</completion_date>
  <primary_completion_date type="Anticipated">June 30, 2023</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 imbalance between goal-directed and habitual behavior</measure>
    <time_frame>2 time points: before and after 6 weeks SCP</time_frame>
    <description>measured by reward devaluation procedure (Hogarth &amp; Chase 2011)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in implicit smoking-related associations</measure>
    <time_frame>3 time points: before and after 6 weeks SCP plus after 3 months</time_frame>
    <description>smoking-related implicit association task (Wiers et al. 2016).</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in attentional bias to smoking cues</measure>
    <time_frame>3 time points: before and after 6 weeks SCP plus after 3 months</time_frame>
    <description>smoking-related dot-probe task (Vollstädt-Klein et al. 2009).</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in smoking urges</measure>
    <time_frame>3 time points: before and after 6 weeks SCP plus after 3 months</time_frame>
    <description>questionnaire of smoking urges (QSU, Müller et al. 2001)); self-report questionnaire; two subscales: &quot;intention and desire to smoke / anticipation of pleasure from smoking&quot; (range 11 - 77) and &quot;anticipation of relief from negative affect and nicotine withdrawal / urgent and overwhelming desire to smoke&quot; (range 10 - 70) high values represent high craving</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in working memory capacity</measure>
    <time_frame>3 time points: before and after 6 weeks SCP plus after 3 months</time_frame>
    <description>Spatial Working Memory task from the Cambridge Automated Neuropsychological Test Automated Battery (Robbins et al. 1994)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in planning ability</measure>
    <time_frame>3 time points: before and after 6 weeks SCP plus after 3 months</time_frame>
    <description>One Touch Stockings of Cambridge task from the Cambridge Automated Neuropsychological Test Automated Battery (Robbins et al. 1994)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in cognitive flexibility</measure>
    <time_frame>3 time points: before and after 6 weeks SCP plus after 3 months</time_frame>
    <description>Internal-External Set Shifting task from the Cambridge Automated Neuropsychological Test Automated Battery (Robbins et al. 1994)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>nicotine consumption</measure>
    <time_frame>3 months follow-up</time_frame>
    <description>self-report</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in neural PIT effect</measure>
    <time_frame>2 time points: before and after 6 weeks SCP</time_frame>
    <description>PIT phase of a choice task (adapted from Hogarth &amp; Chase 2011)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in neural cue reactivity</measure>
    <time_frame>2 time points: before and after 6 weeks SCP</time_frame>
    <description>fMRI cue-reactivity task (Vollstädt-Klein et al. 2011)</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Anticipated">90</enrollment>
  <condition>Tobacco Use Disorder</condition>
  <arm_group>
    <arm_group_label>standard smoking cessation program (SCP)</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>standard smoking cessation program</description>
  </arm_group>
  <arm_group>
    <arm_group_label>SCP + CRT</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>SCP plus cognitive remediation treatment (CRT)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>SCP + ICHT</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>SCP plus an implicit computer-based habit-modifying training (ICHT)</description>
  </arm_group>
  <intervention>
    <intervention_type>Behavioral</intervention_type>
    <intervention_name>standard smoking cessation program (SCP)</intervention_name>
    <description>Each subject will receive standard SCP as group treatment once a week (1 hour) over six weeks. This group therapy is based on behavioural therapy and a psycho-educational approach (for more details see Batra &amp; Buchkremer 2004), and will be carried out by a qualified therapist.</description>
    <arm_group_label>SCP + CRT</arm_group_label>
    <arm_group_label>SCP + ICHT</arm_group_label>
    <arm_group_label>standard smoking cessation program (SCP)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Behavioral</intervention_type>
    <intervention_name>Cognitive remediation treatment (CRT)</intervention_name>
    <description>Cognitive remediation treatment (CRT) employing a chess-based battery of tasks two times per week over six weeks as a group treatment in our outpatient clinic (60 min duration per session).</description>
    <arm_group_label>SCP + CRT</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Behavioral</intervention_type>
    <intervention_name>Implicit computer-based habit-modifying training (ICHT)</intervention_name>
    <description>Implicit computer-based habit-modifying training (ICHT), applied twice a week for six weeks. In this training, the participants perform a two-part training. First, a subliminal presentation (20 ms) of negative valenced primes before smoking-cues in context and secondly, a subliminal presentation of positive valenced primes before potentially reinforcing events.</description>
    <arm_group_label>SCP + ICHT</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  severe tobacco use disorder (TUD) according to DSM-5&#xD;
&#xD;
          -  sufficient ability to communicate with investigators and answer questions in both&#xD;
             written and verbal format&#xD;
&#xD;
          -  ability to provide fully informed consent and to use self-rating scales&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  severe internal, neurological, and/or psychiatric comorbidities; other Axis I mental&#xD;
             disorders other than TUD according to ICD-10 and DSM 5 (except for mild depression,&#xD;
             i.e. F32.0, adjustment disorder and specific phobias) in the last 12 months&#xD;
&#xD;
          -  history of brain injury&#xD;
&#xD;
          -  severe physical diseases&#xD;
&#xD;
          -  common exclusion criteria for MRI (e.g. metal, claustrophobia)&#xD;
&#xD;
          -  positive drug screening (opioids, benzodiazepines, barbiturates, cocaine,&#xD;
             amphetamines)&#xD;
&#xD;
          -  psychotropic medication within the last 14 days&#xD;
&#xD;
          -  pregnancy&#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>Sabine Vollstädt-Klein, Prof. Dr.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Central Institute of Mental Health, Mannheim</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Herta Flor, Prof. Dr.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Central Institute of Mental Health, Mannheim</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Sabine Vollstädt-Klein, Prof. Dr.</last_name>
    <phone>+49-621/1703</phone>
    <phone_ext>3912</phone_ext>
    <email>s.vollstaedt-klein@zi-mannheim.de</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Herta Flor, Prof. Dr.</last_name>
    <phone>+49-621/1703</phone>
    <phone_ext>6302</phone_ext>
    <email>herta.flor@zi-mannheim.de</email>
  </overall_contact_backup>
  <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>
    <status>Recruiting</status>
    <contact>
      <last_name>Sabine Vollstädt-Klein</last_name>
    </contact>
  </location>
  <location_countries>
    <country>Germany</country>
  </location_countries>
  <verification_date>January 2023</verification_date>
  <study_first_submitted>November 28, 2018</study_first_submitted>
  <study_first_submitted_qc>December 4, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 5, 2018</study_first_posted>
  <last_update_submitted>January 24, 2023</last_update_submitted>
  <last_update_submitted_qc>January 24, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">January 26, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Addiction</keyword>
  <keyword>Nicotine</keyword>
  <keyword>Smoking Cessation</keyword>
  <keyword>Relapse</keyword>
  <keyword>Craving</keyword>
  <keyword>habitual behavior</keyword>
  <keyword>cognitive remediation</keyword>
  <keyword>implicit priming</keyword>
  <keyword>pavlovian instrumental transfer</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Tobacco Use Disorder</mesh_term>
    <mesh_term>Behavior, Addictive</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/NCT03764969
org study id: TRR265 C01
nct id: NCT03764969
lead sponsor: 
is fda regulated drug: No
is fda regulated device: No
This study aims to examine the modification of the hypothesized imbalance between
      goal-directed and habitual behavior and its neural correlates in smokers. Two interventions
      will be used as add-on trainings to a smoking cessation program.
In this study, the investigators aim to assess the imbalance between goal-directed and
      habitual behavior, its neural basis and how it can be differentially modified in
      treatment-seeking smokers, using two training interventions. The first intervention is
      cognitive remediation treatment (CRT), also known as cognitive enhancement therapy, focusing
      on improving inhibitory control and executive functions. The second intervention, a
      computer-based habit-modifying training focusing on implicit drug seeking ("implicit
      computer-based habit-modifying training", ICHT) uses a conditioning approach through implicit
      priming and contextual modulation. Indicators of the imbalance will be examined with respect
      to reward devaluation, cue reactivity and a pavlovian instrumental transfer (PIT) paradigm.
      The investigators hypothesize that both interventions change the balance between
      goal-directed and habitual behavior but by different mechanisms. Whereas CRT should directly
      increase cognitive control, in contrast, ICHT should affect the early processing and the
      emotional valence of smoking and smoking cues.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Change in imbalance between goal-directed and habitual behavior
time frame: 2 time points: before and after 6 weeks SCP
description: measured by reward devaluation procedure (Hogarth & Chase 2011)
measure: Change in implicit smoking-related associations
time frame: 3 time points: before and after 6 weeks SCP plus after 3 months
description: smoking-related implicit association task (Wiers et al. 2016).
measure: Change in attentional bias to smoking cues
time frame: 3 time points: before and after 6 weeks SCP plus after 3 months
description: smoking-related dot-probe task (Vollstädt-Klein et al. 2009).
measure: Change in smoking urges
time frame: 3 time points: before and after 6 weeks SCP plus after 3 months
description: questionnaire of smoking urges (QSU, Müller et al. 2001)); self-report questionnaire; two subscales: "intention and desire to smoke / anticipation of pleasure from smoking" (range 11 - 77) and "anticipation of relief from negative affect and nicotine withdrawal / urgent and overwhelming desire to smoke" (range 10 - 70) high values represent high craving
measure: Change in working memory capacity
time frame: 3 time points: before and after 6 weeks SCP plus after 3 months
description: Spatial Working Memory task from the Cambridge Automated Neuropsychological Test Automated Battery (Robbins et al. 1994)
measure: Change in planning ability
time frame: 3 time points: before and after 6 weeks SCP plus after 3 months
description: One Touch Stockings of Cambridge task from the Cambridge Automated Neuropsychological Test Automated Battery (Robbins et al. 1994)
measure: Change in cognitive flexibility
time frame: 3 time points: before and after 6 weeks SCP plus after 3 months
description: Internal-External Set Shifting task from the Cambridge Automated Neuropsychological Test Automated Battery (Robbins et al. 1994)
measure: nicotine consumption
time frame: 3 months follow-up
description: self-report
measure: Change in neural PIT effect
time frame: 2 time points: before and after 6 weeks SCP
description: PIT phase of a choice task (adapted from Hogarth & Chase 2011)
measure: Change in neural cue reactivity
time frame: 2 time points: before and after 6 weeks SCP
description: fMRI cue-reactivity task (Vollstädt-Klein et al. 2011)
arm group label: standard smoking cessation program (SCP)
arm group type: Active Comparator
description: standard smoking cessation program
arm group label: SCP + CRT
arm group type: Experimental
description: SCP plus cognitive remediation treatment (CRT)
arm group label: SCP + ICHT
arm group type: Experimental
description: SCP plus an implicit computer-based habit-modifying training (ICHT)
intervention type: Behavioral
intervention name: standard smoking cessation program (SCP)
description: Each subject will receive standard SCP as group treatment once a week (1 hour) over six weeks. This group therapy is based on behavioural therapy and a psycho-educational approach (for more details see Batra & Buchkremer 2004), and will be carried out by a qualified therapist.
arm group label: SCP + CRT
arm group label: SCP + ICHT
arm group label: standard smoking cessation program (SCP)
intervention type: Behavioral
intervention name: Cognitive remediation treatment (CRT)
description: Cognitive remediation treatment (CRT) employing a chess-based battery of tasks two times per week over six weeks as a group treatment in our outpatient clinic (60 min duration per session).
arm group label: SCP + CRT
intervention type: Behavioral
intervention name: Implicit computer-based habit-modifying training (ICHT)
description: Implicit computer-based habit-modifying training (ICHT), applied twice a week for six weeks. In this training, the participants perform a two-part training. First, a subliminal presentation (20 ms) of negative valenced primes before smoking-cues in context and secondly, a subliminal presentation of positive valenced primes before potentially reinforcing events.
arm group label: SCP + ICHT
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: No
last name: Sabine Vollstädt-Klein, Prof. Dr.
role: Principal Investigator
affiliation: Central Institute of Mental Health, Mannheim
last name: Herta Flor, Prof. Dr.
role: Principal Investigator
affiliation: Central Institute of Mental Health, Mannheim
last name: Sabine Vollstädt-Klein, Prof. Dr.
phone: +49-621/1703
phone ext: 3912
email: s.vollstaedt-klein@zi-mannheim.de
last name: Herta Flor, Prof. Dr.
phone: +49-621/1703
phone ext: 6302
email: herta.flor@zi-mannheim.de
facility: 
status: Recruiting
contact: 
country: Germany
responsible party type: Sponsor
mesh term: Tobacco Use Disorder
mesh term: Behavior, Addictive