xml: <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/NCT06026904</url>
    </required_header>
    <id_info>
      <org_study_id>Y&amp;C</org_study_id>
      <nct_id>NCT06026904</nct_id>
    </id_info>
    <brief_title>The Effects of taVNS on Motivation in MDD With Anhedonia</brief_title>
    <official_title>The Effects of Transcutaneous Auricular Vagus Nerve Stimulation on Motivation in Major Depressive Disorder With Anhedonia</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Anhui Medical University</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>Anhui Medical University</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>
      <is_us_export>Yes</is_us_export>
    </oversight_info>
    <brief_summary>
      <textblock>
        Study of non-invasive transcutaneous auricular vagus nerve stimulation (taVNS) intervention&#xD;
        to improve the reward motivation and response inhibition of major depression disorder and its&#xD;
        brain network mechanism.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        Anhedonia is the core symptom of MDD, which means they have deficits in processing&#xD;
        rewards.MDD get lesser positive feelings than healthy controls from rewards as they could not&#xD;
        use the reward outcome to update the value of a stimulus, which in consequence impedes their&#xD;
        reward motivation or response inhibition and worsen their symptom. We are dedicated to&#xD;
        revealing how reward motivation or response inhibition ability could be intervened by taVNS&#xD;
        intervention, which has been proven is highly relevant to reward motivation and response&#xD;
        inhibition ability. Implementing a safer intervention of taVNS stimulation might help us to&#xD;
        prove a better treatment for patients.&#xD;
  &#xD;
        All patients underwent a medical evaluation that included physical examination and routine&#xD;
        laboratory studies before and after taVNS stimulation treatment. Before and after the taVNS&#xD;
        treatment, depression symptom of each participant was assessed by the Hamilton Depression&#xD;
        Scale and the Beck Depression Self-Rating Scale. The anhedonia severity was evaluated by The&#xD;
        Temporal Experience of Pleasure Scale, the Self-Report Apathy Evaluation Scale, the Positive&#xD;
        Valence system scale and the Motivation and Pleasure Scale. The neuroimaging data are&#xD;
        collected using event-related potentials during the effort reward task and stop signal task&#xD;
        before and after the intervention. Patients were randomly allocated into an active group and&#xD;
        a sham group. We plan to enroll a minimum total sample size of 30 participants in active and&#xD;
        sham group respectively according to the Power and Sample Size program. The decision to&#xD;
        enroll a patient was always made prior to randomization. Each patient will be treated for 4&#xD;
        weeks with 25Hz taVNS. Each participant was interviewed in detail about the adverse event of&#xD;
        the taVNS intervention during the past 4 weeks . Every participant should take part in the&#xD;
        study voluntarily and sign an informed consent form before the study.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Recruiting</overall_status>
    <start_date type="Actual">March 30, 2023</start_date>
    <completion_date type="Anticipated">September 30, 2024</completion_date>
    <primary_completion_date type="Anticipated">December 31, 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>Sequential Assignment</intervention_model>
      <primary_purpose>Treatment</primary_purpose>
      <masking>Triple (Participant, Investigator, Outcomes Assessor)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>Change from baseline in Hamilton Depression Scale</measure>
      <time_frame>baseline;4 weeks post-treatment</time_frame>
      <description>The participants' depression symptom assessed by the Hamilton Depression Scale change from baseline after the treatment.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Change from baseline in Apathy Evaluation Scale</measure>
      <time_frame>baseline;4 weeks post-treatment</time_frame>
      <description>The participants' reward motivation assessed by the Apathy Evaluation Scale change from baseline after the treatment.</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>The change from baseline in behavioral results of effort reward task</measure>
      <time_frame>baseline;4 weeks post-treatment</time_frame>
      <description>Behavioral results changed and discount parameters generated from the model change from baseline after the treatment.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>The change from baseline in event-related brain potentials during the effort reward task</measure>
      <time_frame>baseline;4 weeks post-treatment</time_frame>
      <description>The amplitudes of brain potentials of reward-related positivity and P3 assessed by event-related brain potentials methods change from baseline after the treatment.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>The change from baseline in behavioral results of stop signal task</measure>
      <time_frame>baseline;4 weeks post-treatment</time_frame>
      <description>Behavioral results changed from baseline after the treatment.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>The change from baseline in event-related brain potentials during the stop signal task</measure>
      <time_frame>baseline;4 weeks post-treatment</time_frame>
      <description>Cue-evoked cue-P3 and N2 mean wave amplitude changes and latencies, as well as spectral intensities. Wave amplitude and latency of target-P3 and N2 evoked by target stimuli, and spectral activity.</description>
    </secondary_outcome>
    <number_of_arms>2</number_of_arms>
    <enrollment type="Anticipated">60</enrollment>
    <condition>Intervention</condition>
    <arm_group>
      <arm_group_label>Active Comparator: Real Stimulation</arm_group_label>
      <arm_group_type>Active Comparator</arm_group_type>
      <description>The active Stimulation of taVNS lasted 30 mins. The stimulation protocol is preset to a biphasic impulse frequency of 25 Hz with a stimulation duration of 30 s, followed by a 30 s off phase. Behavior and ERPs datasets should be acquired before the first taVNS session and after the last taVNS session.The electrical current is transmitted by a titanium electrode placed at the cymba conchae.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Sham Comparator: Sham Stimulation</arm_group_label>
      <arm_group_type>Sham Comparator</arm_group_type>
      <description>The active Stimulation of taVNS lasted 30 mins. The stimulation protocol is preset to a biphasic impulse frequency of 25 Hz with a stimulation duration of 30 s, followed by a 30 s off phase. Behavior and ERPs datasets should be acquired before the first taVNS session and after the last taVNS session.The electrical current is transmitted by a titanium electrode placed at the earlobe of the midpoint of the outer ear margin.</description>
    </arm_group>
    <intervention>
      <intervention_type>Device</intervention_type>
      <intervention_name>transcutaneous auricular vagus nerve stimulation</intervention_name>
      <description>taVNS was developed as a non-invasive variant of VNS where the vagus nerve is stimulated through the skin of the auricle, which has become a promising avenue for research and, potentially, treatment of various disorders. Commonly, taVNS is applied via the ear targeting the auricular branch of the vagus nerve, where the stimulation elicits far-field potentials. In line with preclinical studies, acute taVNS enhances invigoration of effort and response inhibition capability.</description>
      <arm_group_label>Active Comparator: Real Stimulation</arm_group_label>
      <arm_group_label>Sham Comparator: Sham Stimulation</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
          Meet the criteria of depression assessed by at least two psychiatrists according to the&#xD;
          fifth version of Diagnostic and Statistical Manual of Mental Disorders.&#xD;
  &#xD;
          The score of Hamilton Depression Rating Scale-17 is larger than 18 and the score of the&#xD;
          Apathy Evaluation scale is lager than 37.&#xD;
  &#xD;
          Patients were taking antidepressants--Selective Serotonin Reuptake Inhibitor(SSRIs) alone.&#xD;
  &#xD;
          Age was between 18 to 60 year old. The education duration was at least 6 years.&#xD;
  &#xD;
          The vision or corrected vision was normal.&#xD;
  &#xD;
          Right handedness.&#xD;
  &#xD;
          No treatment of rTMS, transcranial direct current stimulation, or electroconvulsive therapy&#xD;
          before.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
          History of significant head trauma or neurological disorders.&#xD;
  &#xD;
          Alcohol or drug abuse.&#xD;
  &#xD;
          Focal brain lesions.&#xD;
  &#xD;
          History of seizure.&#xD;
  &#xD;
          First degree relative with epilepsy, significant neurological illness or head trauma,&#xD;
          endocrine disease.&#xD;
  &#xD;
          Significant unstable medical condition.&#xD;
  &#xD;
          Recent aggression or other forms of behavioral dyscontrol.&#xD;
  &#xD;
          Left-handedness.&#xD;
  &#xD;
          Pregnancy.&#xD;
  &#xD;
          Current alcohol or drug abuse&#xD;
  &#xD;
          Inability to provide informed consent.&#xD;
  &#xD;
          Patients with contraindications or factors affecting imaging quality, such as pacemakers,&#xD;
          cochlear implants, or hearts Cerebrovascular metal stent, and metal denture.&#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>Kai Wang, MD</last_name>
      <role>Study Chair</role>
      <affiliation>Anhui Medical University</affiliation>
    </overall_official>
    <overall_official>
      <last_name>Fengqiong Yu, MD</last_name>
      <role>Study Director</role>
      <affiliation>Anhui Medical University</affiliation>
    </overall_official>
    <overall_official>
      <last_name>Rong Ye, Phd</last_name>
      <role>Study Director</role>
      <affiliation>Anhui Medical University</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Fengqiong Yu, MD</last_name>
      <phone>0551-65167281</phone>
      <email>yufengqiong@ahmu.edu.cn</email>
    </overall_contact>
    <overall_contact_backup>
      <last_name>Rong Ye, Phd</last_name>
      <phone>0551-65167281</phone>
      <email>yerong@ahmu.edu.cn</email>
    </overall_contact_backup>
    <location>
      <facility>
        <name>Anhui Medical University</name>
        <address>
          <city>Hefei</city>
          <state>Anhui</state>
          <zip>230032</zip>
          <country>China</country>
        </address>
      </facility>
      <status>Recruiting</status>
      <contact>
        <last_name>Fengqiong Yu, MD</last_name>
        <phone>15955155423</phone>
        <email>yufengqin1@163.com</email>
      </contact>
    </location>
    <location_countries>
      <country>China</country>
    </location_countries>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>August 31, 2023</study_first_submitted>
    <study_first_submitted_qc>August 31, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">September 7, 2023</study_first_posted>
    <last_update_submitted>August 31, 2023</last_update_submitted>
    <last_update_submitted_qc>August 31, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">September 7, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Principal Investigator</responsible_party_type>
      <investigator_affiliation>Anhui Medical University</investigator_affiliation>
      <investigator_full_name>Fengqiong Yu</investigator_full_name>
      <investigator_title>Associate Professor</investigator_title>
    </responsible_party>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Anhedonia</mesh_term>
    </condition_browse>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: 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/NCT06026904
  org study id: Y&C
  nct id: NCT06026904
  lead sponsor: 
  has dmc: Yes
  is fda regulated drug: No
  is fda regulated device: Yes
  is us export: Yes
  Study of non-invasive transcutaneous auricular vagus nerve stimulation (taVNS) intervention
        to improve the reward motivation and response inhibition of major depression disorder and its
        brain network mechanism.
  Anhedonia is the core symptom of MDD, which means they have deficits in processing
        rewards.MDD get lesser positive feelings than healthy controls from rewards as they could not
        use the reward outcome to update the value of a stimulus, which in consequence impedes their
        reward motivation or response inhibition and worsen their symptom. We are dedicated to
        revealing how reward motivation or response inhibition ability could be intervened by taVNS
        intervention, which has been proven is highly relevant to reward motivation and response
        inhibition ability. Implementing a safer intervention of taVNS stimulation might help us to
        prove a better treatment for patients.
  
        All patients underwent a medical evaluation that included physical examination and routine
        laboratory studies before and after taVNS stimulation treatment. Before and after the taVNS
        treatment, depression symptom of each participant was assessed by the Hamilton Depression
        Scale and the Beck Depression Self-Rating Scale. The anhedonia severity was evaluated by The
        Temporal Experience of Pleasure Scale, the Self-Report Apathy Evaluation Scale, the Positive
        Valence system scale and the Motivation and Pleasure Scale. The neuroimaging data are
        collected using event-related potentials during the effort reward task and stop signal task
        before and after the intervention. Patients were randomly allocated into an active group and
        a sham group. We plan to enroll a minimum total sample size of 30 participants in active and
        sham group respectively according to the Power and Sample Size program. The decision to
        enroll a patient was always made prior to randomization. Each patient will be treated for 4
        weeks with 25Hz taVNS. Each participant was interviewed in detail about the adverse event of
        the taVNS intervention during the past 4 weeks . Every participant should take part in the
        study voluntarily and sign an informed consent form before the study.
  allocation: Randomized
  intervention model: Sequential Assignment
  primary purpose: Treatment
  masking: Triple (Participant, Investigator, Outcomes Assessor)
  measure: Change from baseline in Hamilton Depression Scale
  time frame: baseline;4 weeks post-treatment
  description: The participants' depression symptom assessed by the Hamilton Depression Scale change from baseline after the treatment.
  measure: Change from baseline in Apathy Evaluation Scale
  time frame: baseline;4 weeks post-treatment
  description: The participants' reward motivation assessed by the Apathy Evaluation Scale change from baseline after the treatment.
  measure: The change from baseline in behavioral results of effort reward task
  time frame: baseline;4 weeks post-treatment
  description: Behavioral results changed and discount parameters generated from the model change from baseline after the treatment.
  measure: The change from baseline in event-related brain potentials during the effort reward task
  time frame: baseline;4 weeks post-treatment
  description: The amplitudes of brain potentials of reward-related positivity and P3 assessed by event-related brain potentials methods change from baseline after the treatment.
  measure: The change from baseline in behavioral results of stop signal task
  time frame: baseline;4 weeks post-treatment
  description: Behavioral results changed from baseline after the treatment.
  measure: The change from baseline in event-related brain potentials during the stop signal task
  time frame: baseline;4 weeks post-treatment
  description: Cue-evoked cue-P3 and N2 mean wave amplitude changes and latencies, as well as spectral intensities. Wave amplitude and latency of target-P3 and N2 evoked by target stimuli, and spectral activity.
  arm group label: Active Comparator: Real Stimulation
  arm group type: Active Comparator
  description: The active Stimulation of taVNS lasted 30 mins. The stimulation protocol is preset to a biphasic impulse frequency of 25 Hz with a stimulation duration of 30 s, followed by a 30 s off phase. Behavior and ERPs datasets should be acquired before the first taVNS session and after the last taVNS session.The electrical current is transmitted by a titanium electrode placed at the cymba conchae.
  arm group label: Sham Comparator: Sham Stimulation
  arm group type: Sham Comparator
  description: The active Stimulation of taVNS lasted 30 mins. The stimulation protocol is preset to a biphasic impulse frequency of 25 Hz with a stimulation duration of 30 s, followed by a 30 s off phase. Behavior and ERPs datasets should be acquired before the first taVNS session and after the last taVNS session.The electrical current is transmitted by a titanium electrode placed at the earlobe of the midpoint of the outer ear margin.
  intervention type: Device
  intervention name: transcutaneous auricular vagus nerve stimulation
  description: taVNS was developed as a non-invasive variant of VNS where the vagus nerve is stimulated through the skin of the auricle, which has become a promising avenue for research and, potentially, treatment of various disorders. Commonly, taVNS is applied via the ear targeting the auricular branch of the vagus nerve, where the stimulation elicits far-field potentials. In line with preclinical studies, acute taVNS enhances invigoration of effort and response inhibition capability.
  arm group label: Active Comparator: Real Stimulation
  arm group label: Sham Comparator: Sham Stimulation
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: 60 Years
  healthy volunteers: No
  last name: Kai Wang, MD
  role: Study Chair
  affiliation: Anhui Medical University
  last name: Fengqiong Yu, MD
  role: Study Director
  affiliation: Anhui Medical University
  last name: Rong Ye, Phd
  role: Study Director
  affiliation: Anhui Medical University
  last name: Fengqiong Yu, MD
  phone: 0551-65167281
  email: yufengqiong@ahmu.edu.cn
  last name: Rong Ye, Phd
  phone: 0551-65167281
  email: yerong@ahmu.edu.cn
  facility: 
  status: Recruiting
  contact: 
  country: China
  responsible party type: Principal Investigator
  investigator affiliation: Anhui Medical University
  investigator full name: Fengqiong Yu
  investigator title: Associate Professor
  mesh term: Anhedonia