<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/NCT02239809</url>
  </required_header>
  <id_info>
    <org_study_id>239/2012</org_study_id>
    <nct_id>NCT02239809</nct_id>
  </id_info>
  <brief_title>Electrical Stimulation in Patients With Unipolar Major Depression</brief_title>
  <acronym>TREND1</acronym>
  <official_title>Double Blinded Randomized Trial of sTNS as Adjuvant Treatment for Major Unipolar Depressive Disorder.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Hospital do Coracao</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Hospital do Coracao</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Double Blinded Randomized Trial of sTNS as adjuvant treatment for Major Unipolar Depressive&#xD;
      Disorder. The primary objective is to assess the safety and tolerability of an implantable&#xD;
      sTNS of the V1 branch of the trigeminal nerve as an adjunctive treatment for adult patients&#xD;
      with the diagnosis of unipolar MDD (Major Depressive Disorder).&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>May 2014</start_date>
  <completion_date type="Actual">July 2016</completion_date>
  <primary_completion_date type="Actual">May 2016</primary_completion_date>
  <phase>Phase 2</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>Triple (Participant, Care Provider, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Identify a efficacy of sTNS of the V1 branch of the trigeminal nerve</measure>
    <time_frame>12 months</time_frame>
    <description>We will use the Hamilton Rating Scale for Depression (HRSD) 17 scores as the main outcome measure to assess the efficacy of sTNS of the V1 branch of the trigeminal nerve as adjunctive treatment for MDD.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Identify the tolerability of sTNS stimulation</measure>
    <time_frame>12 months</time_frame>
    <description>Tolerability will be evaluated by the records of adverse effects observed during the randomized, open stimulation. We will apply the Ugvalg for Kliniske Undersgelser (UKU) scale at all visits for all patients and to compare scores between groups. Adverse events will be categorized using the MedDRA Medical Dictionary for Regulatory Activities. Complications reported by active and sham stimulation groups will be compared. The complication risk will be calculated based on the overall study duration.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Identify the long-term recurrence rate of sTNS therapy</measure>
    <time_frame>12 months</time_frame>
    <description>We will calculate the recurrence rate of all participants at the end of the open label prospective follow-up. Recurrence is defined as return of HAM-17 scores equal to or superior to the original, after the patient has lodged during partial response (20% decrease of the initial score) or complete response (50% decrease of the initial score).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Identify the duration of the placebo effect</measure>
    <time_frame>12 months</time_frame>
    <description>To evaluate the duration of the placebo effect in participants randomized to sham stimulation during the initial 12 weeks of the trial. The mean, median and the standard deviation of the interval time to recurrence will be calculated on placebo stimulation.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">20</enrollment>
  <condition>Depression</condition>
  <arm_group>
    <arm_group_label>Active Stimulation</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Patients assigned to active stimulation arm will receive electrical stimulation during the study.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo Stimulation</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Patients assigned to the placebo arm did not receive stimulation electrical stimulation for 24 weeks. After this period the participants randomized to sham stimulation will be moved to the active stimulation and will be followed until study completion.</description>
  </arm_group>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Stimulation of the trigeminal nerve (active stimulation)</intervention_name>
    <description>Participants will be randomized to active vs. sham stimulation during a period of 24 weeks with a one-way cross over at 12 weeks.&#xD;
After 12 weeks, the participants receiving active electrical stimulation will continue under active stimulation until completion of the study.&#xD;
Participants randomized to sham stimulation will be shifted to active stimulation and will be followed-up until completion of the study.&#xD;
The study will be unblinded after 6 months of randomized stimulation. The second part of the study will be an open label prospective trial for evaluate long-term follow-up. The duration of the open label trial will be more 24 weeks.</description>
    <arm_group_label>Active Stimulation</arm_group_label>
    <other_name>Electrical Stimulation</other_name>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Placebo stimulation of the trigeminal nerve (placebo)</intervention_name>
    <description>Participants will be randomized to active vs. sham stimulation during a period of 24 weeks with a one-way cross over at 12 weeks. Patients of the placebo group will be implanted with a lead in the V1 branch of the trigeminal nerve, but will not receive stimulation.&#xD;
After 12 weeks, the participants receiving active electrical stimulation will continue under active stimulation until completion of the study.&#xD;
Participants randomized to placebo stimulation will be shifted to active stimulation and will be followed-up until completion of the study.&#xD;
The study will be unblinded after 6 months of randomized stimulation. The second part of the study will be an open label prospective trial for evaluate long-term follow-up. The duration of the open label trial will be more 24 weeks.</description>
    <arm_group_label>Placebo Stimulation</arm_group_label>
    <other_name>Sham Eletrical Stimulation</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Outpatients with non-psychotic, unipolar Major Depressive Disorder assessed via the&#xD;
             MINI structured interview and legally capacitated to sign the informed consent for&#xD;
             participation in the study;&#xD;
&#xD;
          -  A score of ≥ 14 on the HAM-D17 with Item 1 (depressed mood) ≥ 2;&#xD;
&#xD;
          -  A history of treatment failure with at least 3 adequate trials antidepressants over&#xD;
             the previous 6 weeks and less than 6 medications, with no change in antidepressant&#xD;
             medication or dose within the previous 6 weeks, and ongoing use of at least one&#xD;
             antidepressant (which will continue during participation in the study);&#xD;
&#xD;
          -  Patients with suicidal ideation are eligible only if the thoughts of death or of life&#xD;
             not being worth living are not accompanied by a plan or intention for self-harm and&#xD;
             lack of self-harming attempt in the past 6 months;&#xD;
&#xD;
          -  Patients with appropriate support to be compliant with the study protocol.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patient is mentally or legally incapacitated, unable to give informed consent.&#xD;
&#xD;
          -  Patients with psychosis (psychotic depression, schizophrenia, or schizoaffective&#xD;
             diagnoses (lifetime); bipolar disorder (lifetime); dementia (lifetime); delirium or&#xD;
             any substance abuse disorder within the past 6 months; eating disorder within the past&#xD;
             year; obsessive-compulsive disorder (lifetime); post-traumatic stress disorder within&#xD;
             the past year; acute risk for suicide or self-injurious behavior. Patients with&#xD;
             diagnostic uncertainty or ambiguity (e.g. rule-out pseudo-dementia of depression) will&#xD;
             be excluded.&#xD;
&#xD;
          -  Patients currently receiving more than six medications for treatment of MDD;&#xD;
&#xD;
          -  Patients with exposure to ECT or rTMS or any investigational treatment (for any&#xD;
             disorder) within the past 6 months;&#xD;
&#xD;
          -  Prior VNS and/or DBS therapy (lifetime);&#xD;
&#xD;
          -  Past history of skull fracture; cranial surgery entering the calvarium; space&#xD;
             occupying intracranial lesion; stroke, CVA, or TIAs; cerebral aneurysm; Parkinson's or&#xD;
             Huntington's disease; or Multiple Sclerosis;&#xD;
&#xD;
          -  Current pregnancy, breast feeding, plans to become pregnant during the study, or not&#xD;
             using a medically accepted means of contraception;&#xD;
&#xD;
          -  Other medical conditions that would increase the risk of infection or surgical related&#xD;
             morbidity and/or would affect compliance with the study protocol.&#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>Alessandra Gorgulho, MD, MSc</last_name>
    <role>Principal Investigator</role>
    <affiliation>Hospital do Coracao</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Antonio De Salles, M.D., Ph.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Hospital do Coração</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Otavio Berwanger, MD,PhD</last_name>
    <role>Study Director</role>
    <affiliation>Hospital do Coração</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Hospital do Coracao</name>
      <address>
        <city>Sao Paulo</city>
        <zip>040005-000</zip>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Brazil</country>
  </location_countries>
  <verification_date>September 2016</verification_date>
  <study_first_submitted>August 21, 2014</study_first_submitted>
  <study_first_submitted_qc>September 11, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 15, 2014</study_first_posted>
  <last_update_submitted>September 28, 2016</last_update_submitted>
  <last_update_submitted_qc>September 28, 2016</last_update_submitted_qc>
  <last_update_posted type="Estimate">September 29, 2016</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Electrodes, Implanted</keyword>
  <keyword>Electric Stimulation Therapy</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Depression</mesh_term>
    <mesh_term>Depressive Disorder</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/NCT02239809
org study id: 239/2012
nct id: NCT02239809
lead sponsor: 
has dmc: Yes
Double Blinded Randomized Trial of sTNS as adjuvant treatment for Major Unipolar Depressive
      Disorder. The primary objective is to assess the safety and tolerability of an implantable
      sTNS of the V1 branch of the trigeminal nerve as an adjunctive treatment for adult patients
      with the diagnosis of unipolar MDD (Major Depressive Disorder).
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Triple (Participant, Care Provider, Investigator)
measure: Identify a efficacy of sTNS of the V1 branch of the trigeminal nerve
time frame: 12 months
description: We will use the Hamilton Rating Scale for Depression (HRSD) 17 scores as the main outcome measure to assess the efficacy of sTNS of the V1 branch of the trigeminal nerve as adjunctive treatment for MDD.
measure: Identify the tolerability of sTNS stimulation
time frame: 12 months
description: Tolerability will be evaluated by the records of adverse effects observed during the randomized, open stimulation. We will apply the Ugvalg for Kliniske Undersgelser (UKU) scale at all visits for all patients and to compare scores between groups. Adverse events will be categorized using the MedDRA Medical Dictionary for Regulatory Activities. Complications reported by active and sham stimulation groups will be compared. The complication risk will be calculated based on the overall study duration.
measure: Identify the long-term recurrence rate of sTNS therapy
time frame: 12 months
description: We will calculate the recurrence rate of all participants at the end of the open label prospective follow-up. Recurrence is defined as return of HAM-17 scores equal to or superior to the original, after the patient has lodged during partial response (20% decrease of the initial score) or complete response (50% decrease of the initial score).
measure: Identify the duration of the placebo effect
time frame: 12 months
description: To evaluate the duration of the placebo effect in participants randomized to sham stimulation during the initial 12 weeks of the trial. The mean, median and the standard deviation of the interval time to recurrence will be calculated on placebo stimulation.
arm group label: Active Stimulation
arm group type: Active Comparator
description: Patients assigned to active stimulation arm will receive electrical stimulation during the study.
arm group label: Placebo Stimulation
arm group type: Placebo Comparator
description: Patients assigned to the placebo arm did not receive stimulation electrical stimulation for 24 weeks. After this period the participants randomized to sham stimulation will be moved to the active stimulation and will be followed until study completion.
intervention type: Procedure
intervention name: Stimulation of the trigeminal nerve (active stimulation)
description: Participants will be randomized to active vs. sham stimulation during a period of 24 weeks with a one-way cross over at 12 weeks.
After 12 weeks, the participants receiving active electrical stimulation will continue under active stimulation until completion of the study.
Participants randomized to sham stimulation will be shifted to active stimulation and will be followed-up until completion of the study.
The study will be unblinded after 6 months of randomized stimulation. The second part of the study will be an open label prospective trial for evaluate long-term follow-up. The duration of the open label trial will be more 24 weeks.
arm group label: Active Stimulation
other name: Electrical Stimulation
intervention type: Procedure
intervention name: Placebo stimulation of the trigeminal nerve (placebo)
description: Participants will be randomized to active vs. sham stimulation during a period of 24 weeks with a one-way cross over at 12 weeks. Patients of the placebo group will be implanted with a lead in the V1 branch of the trigeminal nerve, but will not receive stimulation.
After 12 weeks, the participants receiving active electrical stimulation will continue under active stimulation until completion of the study.
Participants randomized to placebo stimulation will be shifted to active stimulation and will be followed-up until completion of the study.
The study will be unblinded after 6 months of randomized stimulation. The second part of the study will be an open label prospective trial for evaluate long-term follow-up. The duration of the open label trial will be more 24 weeks.
arm group label: Placebo Stimulation
other name: Sham Eletrical Stimulation
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: No
last name: Alessandra Gorgulho, MD, MSc
role: Principal Investigator
affiliation: Hospital do Coracao
last name: Antonio De Salles, M.D., Ph.D.
role: Principal Investigator
affiliation: Hospital do Coração
last name: Otavio Berwanger, MD,PhD
role: Study Director
affiliation: Hospital do Coração
facility: 
country: Brazil
responsible party type: Sponsor
mesh term: Depression
mesh term: Depressive Disorder