<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/NCT03773523</url>
  </required_header>
  <id_info>
    <org_study_id>PSYCH-2018-27116</org_study_id>
    <nct_id>NCT03773523</nct_id>
  </id_info>
  <brief_title>Neuromodulation and Cognitive Training in Opioid Use Disorder</brief_title>
  <official_title>Neuromodulation and Cognitive Training in Opioid Use Disorder</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Minnesota</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Minnesota</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>Yes</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The relapsing nature of opioid use disorder is a major obstacle to successful treatment.&#xD;
      About 90% of those entering treatment will relapse within one year. To improve treatment&#xD;
      outcome, new interventions targeting the underlying brain biomarkers of relapse vulnerability&#xD;
      hold significant promise in reducing this critical public health problem. Transcranial direct&#xD;
      current stimulation (tDCS) is a non-invasive brain stimulation technique that can modulate&#xD;
      brain connectivity.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Cognitive flexibility, the ability to change maladaptive behavior, depends on dorsolateral&#xD;
      prefrontal cortex (DLPFC) input to the nucleus accumbens (NAcc; Gruber, Hussain, and&#xD;
      O'Donnell 2009). DLPFC stimulation may increase input to NAcc to facilitate proper selection&#xD;
      of goal-directed behavior and may also decrease craving in individuals with substance use&#xD;
      disorder (Boggio et al. 2008).&#xD;
&#xD;
      We will use transcranial direct current stimulation (tDCS) to stimulate the DLPFC. TDCS is a&#xD;
      non-invasive brain stimulation technique that can modulate brain connectivity. TDCS involves&#xD;
      applying a weak electrical current (2mA or less) to the scalp via anodal and cathodal&#xD;
      electrode sponges, causing either increases or decreases in cortical excitability,&#xD;
      respectively. Research has shown in both healthy subjects and patients (e.g. Alzheimer's&#xD;
      disease, Parkinson's disease, stroke, and depression) that tDCS has the potential to modulate&#xD;
      synaptic strengthening and neurotransmitter-dependent plasticity underlying changes in&#xD;
      behavior and learning (Lang et al. 2005).&#xD;
&#xD;
      We are anticipating enrollment of 30 participants. Fifteen participants will be randomly&#xD;
      assigned to the interventional tDCS condition, while 15 participants will be randomly&#xD;
      assigned to sham tDCS. Both conditions will undergo five sessions of tDCS across five days.&#xD;
      Participants will undergo pre- and post-tDCS MRI scans, in addition to clinical interviews&#xD;
      and questionnaires. Follow-up interviews will be conducted in person 1 and 2 months after&#xD;
      intervention completion to inquire about relapse status.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">August 1, 2019</start_date>
  <completion_date type="Anticipated">October 2023</completion_date>
  <primary_completion_date type="Anticipated">October 1, 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>
    <intervention_model_description>This study is randomized, double-blind, and sham-controlled. Participants will be randomly assigned to either active or sham tDCS.</intervention_model_description>
    <primary_purpose>Device Feasibility</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
    <masking_description>Participants will not be informed on their assigned protocol. During consent, they will be informed that there is a 50% chance of being assigned either to the group receiving active tDCS or the group receiving sham tDCS.&#xD;
The Principal Investigator and research staff will also be blind to the condition the participant is assigned to.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Change in brain functional connectivity as measured by functional magnetic resonance imaging</measure>
    <time_frame>Change between baseline and 1-week follow-up</time_frame>
    <description>Investigators will measure magnitude of functional connectivity in between nucleus accumbens (NAcc) and prefrontal cortex (PFC) both at baseline and at follow-up and compare the magnitude of change between the active-tDCS and sham-tDCS groups.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Correlation between functional connectivity change and craving scores</measure>
    <time_frame>Data collection will be during 2 and 3 weeks of abstinence</time_frame>
    <description>Investigators will (1) compare change in craving scores (difference in craving scores between 2 and 3 weeks of abstinence) between active-tDCS and sham-tDCS groups and (2) conduct parametric correlations between functional connectivity change and change in craving scores.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Correlation between functional connectivity change and clinical outcome</measure>
    <time_frame>Between 2 weeks of abstinence and 2 months later</time_frame>
    <description>Investigators will record relapse status during the 2 months following treatment discharge.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">30</enrollment>
  <condition>Opioid-use Disorder</condition>
  <condition>Opioid Dependence</condition>
  <condition>Opioid Abuse</condition>
  <arm_group>
    <arm_group_label>Experimental: active tDCS</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Subjects that are randomly assigned to this arm will undergo 5 sessions of tDCS.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Sham Comparator: sham tDCS</arm_group_label>
    <arm_group_type>Sham Comparator</arm_group_type>
    <description>Subjects randomly assigned to sham-tDCS will receive very low current stimulation at the beginning and end of the session, mimicking the feeling of current stimulation in the scalp, but not reaching levels that will stimulate brain function. There will be a total of 5 sham tDCS sessions.</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Transcranial Direct Current Stimulation (tDCS)</intervention_name>
    <description>tDCS will be performed with Neuroelectrics Starstim Enobio 20, a non-invasive investigational device that has been labeled as a non-significant risk device by the FDA. This study is regulated by the FDA as an Abbreviated IDE. It has built-in safety mechanisms which allow for immediate cessation of stimulation if the subject becomes uncomfortable. The current will be administered via two electrode sponges for 25 mins with 1-2 milliamperes. These administration protocols are in line with protocols that have outlined safe administration (Nitsche 2007; 2008). No side-effects have been reported with the exception of slight itching under the electrode and occasional occurrence of headache, fatigue, or nausea (Poreisz 2007). Electrodes placement: dorsolateral prefrontal cortex (DLPFC); cathode on left DLPFC, anode on right DLPFC.</description>
    <arm_group_label>Experimental: active tDCS</arm_group_label>
    <arm_group_label>Sham Comparator: sham tDCS</arm_group_label>
    <other_name>Starstim</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  20 abstinent individuals (18-60 years old; 1-2 weeks of abstinence) who meet DSM-V&#xD;
             criteria for opioid use disorder (OUD) will be recruited from the Lodging Plus&#xD;
             Program, part of University of Minnesota Medical Center&#xD;
&#xD;
          -  This 28-day program provides a supervised environment to treat individuals with OUD in&#xD;
             which patients receive random drug screenings. Lodging Plus has 50 beds and admits an&#xD;
             average of 20 patients per week and about 50% of patients admitted have a diagnosis of&#xD;
             opioid use disorder.&#xD;
&#xD;
          -  Ability to provide written consent and comply with study procedures, meet the&#xD;
             Diagnostic and Statistical Manual of Mental Disorders (DSM-V) diagnostic criteria for&#xD;
             OUD. Subjects may have current comorbid drug use, but their primary substance use&#xD;
             disorder diagnosis needs to be based on opioid use. Subjects must have the intention&#xD;
             to remain in the Lodging Plus program (4 weeks) until the end of the intervention&#xD;
             portion of the study. Vulnerable populations will not be included.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Any medical condition or treatment with neurological sequelae (i.e. stroke, tumor,&#xD;
             loss of consciousness&gt;30 min, HIV)&#xD;
&#xD;
          -  A head injury resulting in a skull fracture or a loss of consciousness exceeding 30&#xD;
             minutes (i.e., moderate or severe TBI)&#xD;
&#xD;
          -  Any contraindications for tDCS or MRI scanning (tDCS contraindication: history of&#xD;
             seizures; MRI contraindications; metal implants, pacemakers or any other implanted&#xD;
             electrical device, injury with metal, braces, dental implants, non-removable body&#xD;
             piercings, pregnancy, breathing or moving disorder)&#xD;
&#xD;
          -  DSM-V criteria for psychiatric disorder, may have a lifetime diagnosis of depression&#xD;
&#xD;
          -  Presence of a condition that would render study measures difficult or impossible to&#xD;
             administer or interpret&#xD;
&#xD;
          -  Age outside the range of 18 to 60&#xD;
&#xD;
          -  Primary current substance use disorder diagnosis on a substance other than opioid&#xD;
             except for caffeine or nicotine&#xD;
&#xD;
          -  Clinical evidence for Wernicke-Korsakoff syndrome&#xD;
&#xD;
          -  Nicotine use will be recorded.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>60 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Jazmin Y Camchong, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Minnesota</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Kelvin O Lim, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Minnesota</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Jazmin Y Camchong, PhD</last_name>
    <phone>(612) 624-0134</phone>
    <email>camch002@umn.edu</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Lamisa N Chowdhury, BS</last_name>
    <phone>(612) 626-6808</phone>
    <email>chow0082@umn.edu</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>University of Minnesota</name>
      <address>
        <city>Minneapolis</city>
        <state>Minnesota</state>
        <zip>55414</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Jazmin Y Camchong, PhD</last_name>
      <phone>612-624-0134</phone>
      <email>camch002@umn.edu</email>
    </contact>
    <investigator>
      <last_name>Jazmin Y Camchong, PhD</last_name>
      <role>Principal Investigator</role>
    </investigator>
    <investigator>
      <last_name>Kelvin O Lim, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <reference>
    <citation>Camchong J, Macdonald AW 3rd, Mueller BA, Nelson B, Specker S, Slaymaker V, Lim KO. Changes in resting functional connectivity during abstinence in stimulant use disorder: a preliminary comparison of relapsers and abstainers. Drug Alcohol Depend. 2014 Jun 1;139:145-51. doi: 10.1016/j.drugalcdep.2014.03.024. Epub 2014 Mar 29.</citation>
    <PMID>24745476</PMID>
  </reference>
  <reference>
    <citation>Camchong J, Stenger A, Fein G. Resting-state synchrony during early alcohol abstinence can predict subsequent relapse. Cereb Cortex. 2013 Sep;23(9):2086-99. doi: 10.1093/cercor/bhs190. Epub 2012 Jul 20.</citation>
    <PMID>22819968</PMID>
  </reference>
  <reference>
    <citation>Camchong J, Stenger VA, Fein G. Resting-state synchrony in short-term versus long-term abstinent alcoholics. Alcohol Clin Exp Res. 2013 May;37(5):794-803. doi: 10.1111/acer.12037. Epub 2013 Feb 19.</citation>
    <PMID>23421812</PMID>
  </reference>
  <verification_date>March 2023</verification_date>
  <study_first_submitted>December 10, 2018</study_first_submitted>
  <study_first_submitted_qc>December 10, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 12, 2018</study_first_posted>
  <last_update_submitted>March 6, 2023</last_update_submitted>
  <last_update_submitted_qc>March 6, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">March 7, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>tDCS</keyword>
  <keyword>Transcranial Direct Current Stimulation</keyword>
  <keyword>MRI</keyword>
  <keyword>Opioid dependence</keyword>
  <keyword>Opioids</keyword>
  <keyword>Buprenorphine</keyword>
  <keyword>Suboxone</keyword>
  <keyword>Lodging Plus</keyword>
  <keyword>Fairview Lodging Plus</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Opioid-Related Disorders</mesh_term>
    <mesh_term>Substance-Related Disorders</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Undecided</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/NCT03773523
org study id: PSYCH-2018-27116
nct id: NCT03773523
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: Yes
The relapsing nature of opioid use disorder is a major obstacle to successful treatment.
      About 90% of those entering treatment will relapse within one year. To improve treatment
      outcome, new interventions targeting the underlying brain biomarkers of relapse vulnerability
      hold significant promise in reducing this critical public health problem. Transcranial direct
      current stimulation (tDCS) is a non-invasive brain stimulation technique that can modulate
      brain connectivity.
Cognitive flexibility, the ability to change maladaptive behavior, depends on dorsolateral
      prefrontal cortex (DLPFC) input to the nucleus accumbens (NAcc; Gruber, Hussain, and
      O'Donnell 2009). DLPFC stimulation may increase input to NAcc to facilitate proper selection
      of goal-directed behavior and may also decrease craving in individuals with substance use
      disorder (Boggio et al. 2008).

      We will use transcranial direct current stimulation (tDCS) to stimulate the DLPFC. TDCS is a
      non-invasive brain stimulation technique that can modulate brain connectivity. TDCS involves
      applying a weak electrical current (2mA or less) to the scalp via anodal and cathodal
      electrode sponges, causing either increases or decreases in cortical excitability,
      respectively. Research has shown in both healthy subjects and patients (e.g. Alzheimer's
      disease, Parkinson's disease, stroke, and depression) that tDCS has the potential to modulate
      synaptic strengthening and neurotransmitter-dependent plasticity underlying changes in
      behavior and learning (Lang et al. 2005).

      We are anticipating enrollment of 30 participants. Fifteen participants will be randomly
      assigned to the interventional tDCS condition, while 15 participants will be randomly
      assigned to sham tDCS. Both conditions will undergo five sessions of tDCS across five days.
      Participants will undergo pre- and post-tDCS MRI scans, in addition to clinical interviews
      and questionnaires. Follow-up interviews will be conducted in person 1 and 2 months after
      intervention completion to inquire about relapse status.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: This study is randomized, double-blind, and sham-controlled. Participants will be randomly assigned to either active or sham tDCS.
primary purpose: Device Feasibility
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
masking description: Participants will not be informed on their assigned protocol. During consent, they will be informed that there is a 50% chance of being assigned either to the group receiving active tDCS or the group receiving sham tDCS.
The Principal Investigator and research staff will also be blind to the condition the participant is assigned to.
measure: Change in brain functional connectivity as measured by functional magnetic resonance imaging
time frame: Change between baseline and 1-week follow-up
description: Investigators will measure magnitude of functional connectivity in between nucleus accumbens (NAcc) and prefrontal cortex (PFC) both at baseline and at follow-up and compare the magnitude of change between the active-tDCS and sham-tDCS groups.
measure: Correlation between functional connectivity change and craving scores
time frame: Data collection will be during 2 and 3 weeks of abstinence
description: Investigators will (1) compare change in craving scores (difference in craving scores between 2 and 3 weeks of abstinence) between active-tDCS and sham-tDCS groups and (2) conduct parametric correlations between functional connectivity change and change in craving scores.
measure: Correlation between functional connectivity change and clinical outcome
time frame: Between 2 weeks of abstinence and 2 months later
description: Investigators will record relapse status during the 2 months following treatment discharge.
arm group label: Experimental: active tDCS
arm group type: Experimental
description: Subjects that are randomly assigned to this arm will undergo 5 sessions of tDCS.
arm group label: Sham Comparator: sham tDCS
arm group type: Sham Comparator
description: Subjects randomly assigned to sham-tDCS will receive very low current stimulation at the beginning and end of the session, mimicking the feeling of current stimulation in the scalp, but not reaching levels that will stimulate brain function. There will be a total of 5 sham tDCS sessions.
intervention type: Device
intervention name: Transcranial Direct Current Stimulation (tDCS)
description: tDCS will be performed with Neuroelectrics Starstim Enobio 20, a non-invasive investigational device that has been labeled as a non-significant risk device by the FDA. This study is regulated by the FDA as an Abbreviated IDE. It has built-in safety mechanisms which allow for immediate cessation of stimulation if the subject becomes uncomfortable. The current will be administered via two electrode sponges for 25 mins with 1-2 milliamperes. These administration protocols are in line with protocols that have outlined safe administration (Nitsche 2007; 2008). No side-effects have been reported with the exception of slight itching under the electrode and occasional occurrence of headache, fatigue, or nausea (Poreisz 2007). Electrodes placement: dorsolateral prefrontal cortex (DLPFC); cathode on left DLPFC, anode on right DLPFC.
arm group label: Experimental: active tDCS
arm group label: Sham Comparator: sham tDCS
other name: Starstim
criteria: 
gender: All
minimum age: 18 Years
maximum age: 60 Years
healthy volunteers: No
last name: Jazmin Y Camchong, PhD
role: Principal Investigator
affiliation: University of Minnesota
last name: Kelvin O Lim, MD
role: Principal Investigator
affiliation: University of Minnesota
last name: Jazmin Y Camchong, PhD
phone: (612) 624-0134
email: camch002@umn.edu
last name: Lamisa N Chowdhury, BS
phone: (612) 626-6808
email: chow0082@umn.edu
facility: 
status: Recruiting
contact: 
investigator: 
investigator: 
country: United States
citation: Camchong J, Macdonald AW 3rd, Mueller BA, Nelson B, Specker S, Slaymaker V, Lim KO. Changes in resting functional connectivity during abstinence in stimulant use disorder: a preliminary comparison of relapsers and abstainers. Drug Alcohol Depend. 2014 Jun 1;139:145-51. doi: 10.1016/j.drugalcdep.2014.03.024. Epub 2014 Mar 29.
PMID: 24745476
citation: Camchong J, Stenger A, Fein G. Resting-state synchrony during early alcohol abstinence can predict subsequent relapse. Cereb Cortex. 2013 Sep;23(9):2086-99. doi: 10.1093/cercor/bhs190. Epub 2012 Jul 20.
PMID: 22819968
citation: Camchong J, Stenger VA, Fein G. Resting-state synchrony in short-term versus long-term abstinent alcoholics. Alcohol Clin Exp Res. 2013 May;37(5):794-803. doi: 10.1111/acer.12037. Epub 2013 Feb 19.
PMID: 23421812
responsible party type: Sponsor
mesh term: Opioid-Related Disorders
mesh term: Substance-Related Disorders
sharing ipd: Undecided