<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/NCT03254017</url>
  </required_header>
  <id_info>
    <org_study_id>Habenula DBS</org_study_id>
    <nct_id>NCT03254017</nct_id>
  </id_info>
  <brief_title>Remotely Programmed Deep Brain Stimulation of the Bilateral Habenula for Treatment- Resistant Major Depression: An Open Label Pilot Trial</brief_title>
  <official_title>Remotely Programmed Deep Brain Stimulation of the Bilateral Habenula for Treatment- Resistant Major Depression: An Open Label Pilot Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Ruijin Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Ruijin Hospital</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The habenula(Hb) is an epithalamic structure located at the center of the dorsal diencephalic&#xD;
      conduction system, a pathway involved in linking forebrain to midbrain regions. An increasing&#xD;
      number of studies indicates that that overactivity in the lateral habeluna(LHb) is present&#xD;
      during depressed states, where it could drive the changes in midbrain activity linked to&#xD;
      depression. Deep brain stimulation(DBS) of the major afferent bundle (i.e., stria medullaris&#xD;
      thalami) of the LHb can treat treatment-resistant major depression(TRD). There is no clinical&#xD;
      case of directly stimulating habeluna for treatment TRD. This research will investigate&#xD;
      effectiveness bilateral DBS to habenula for patients with TRD.&#xD;
&#xD;
      Programming is a crucial aspect of DBS which directly influences its therapeutic efficacy.&#xD;
      Researchers need to ascertain optimum stimulation parameters to help patients achieve optimal&#xD;
      control of clinical symptoms. Remote programming of DBS can markedly improve patient&#xD;
      convenience, minimize risk of infection and total treatment time and lead to an overall&#xD;
      benefit for doctors and patients alike. This research will also investigate safety and&#xD;
      benefit of remote programming of DBS.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    logistics reasons&#xD;
  </why_stopped>
  <start_date type="Actual">July 24, 2017</start_date>
  <completion_date type="Actual">August 30, 2019</completion_date>
  <primary_completion_date type="Actual">November 30, 2018</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <intervention_model_description>all subjects will receive bilateral surgical implantation of DBS system.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change in the Montgomery-Asberg Depression Rating Scale</measure>
    <time_frame>Baseline (preoperative),Biweekly after onset of the DBS system,3 months,6 months, 9 months, 12 months</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in the Hamilton Depression Scale</measure>
    <time_frame>Baseline（preoperative）,3 months, 6 months,9 months, 12months</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in the Hamilton Anxiety Scale</measure>
    <time_frame>Baseline（preoperative）,3 months, 6 months,9 months, 12months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in the Quality of Life Assessment (SF-36)</measure>
    <time_frame>Baseline（preoperative）,3 months, 6 months,9 months, 12 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Neuropsychological measures(Scores of cogstate battery)</measure>
    <time_frame>Baseline（preoperative）,6 months,12 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in the Hamilton Anxiety Scale</measure>
    <time_frame>Baseline（preoperative）,3 months, 6 months,9 months, 12 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in the WHO-BREF</measure>
    <time_frame>Baseline（preoperative）,3 months,6 months,9 months, 12 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Young Manic Rating Scale</measure>
    <time_frame>Baseline (preoperative),Biweekly after onset of the DBS system,3 months,6 months, 9 months, 12 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Chang in Pittsburgh Sleep Quality Index</measure>
    <time_frame>Baseline（preoperative）,3 months,6 months,9 months, 12 months</time_frame>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">2</enrollment>
  <condition>Treatment Resistant Major Depressive Disorder</condition>
  <arm_group>
    <arm_group_label>Experimental Deep Brain Stimulation</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Device：Suzhou Sceneray® DBS system</description>
  </arm_group>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Bilateral surgical implantation of DBS system to Habeluna</intervention_name>
    <description>The SceneRay DBS device utilized in the present study is a double-channel device designed and manufactured by Suzhou Scene-Ray Medical Co., Ltd. The DBS system includes a dual-channel neurostimulator kit, lead kit, extension kit, clinician-operated wireless programmer, test stimulator, and patient controller. The lead (diameter =1.27 mm) contains four stimulating contacts made of platinumiridium alloy. The length of each contact is 1.5 mm, and interval spaces are 0.5 mm. This device shares the same basic principles utilized by Medtronic products, with unique wireless programming and electrode fixing designs. The amplitude (0-10 V), pulse width (60-960 ms), and frequency (1-1,600 Hz) can be programmed, and different frequencies may be utilized in the left and right hemispheres using this type of dual-channel IPG.</description>
    <arm_group_label>Experimental Deep Brain Stimulation</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Follow-up Period</intervention_name>
    <description>The researchers will remotely program the DBS biweekly after opening the stimulator and face to face test the patients' cognitive function every half year. Montgomery-Asberg Depression Rating Scale will be tested biweekly until the Programmed parameter has stable therapeutic efficacy and then tested after 3 months, 6 months, 9 months and 12 months.The other neuropsychological scales will be test on 3 months, 6 months, 9 months and 12 months.</description>
    <arm_group_label>Experimental Deep Brain Stimulation</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age 18-65 years old&#xD;
&#xD;
          -  Proficiency in Mandarin language;&#xD;
&#xD;
          -  DSM-IV diagnosis of Majior depression disorder;&#xD;
&#xD;
          -  Current episode duration ≥ 2 years;&#xD;
&#xD;
          -  Failure to respond to a minimum of four different antidepressant treatments;&#xD;
&#xD;
          -  Failure or intolerance of an adequate course of electroconvulsive therapy (ECT) during&#xD;
             any episode;&#xD;
&#xD;
          -  Capacity to provide informed consent (understanding of the study purpose and methods);&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Schizophrenia or history of psychosis unrelated to MDD;&#xD;
&#xD;
          -  Antisocial personality disorder, dementia, current tic disorder;&#xD;
&#xD;
          -  Past stereotactic neurosurgical intervention;&#xD;
&#xD;
          -  Alcohol or substance abuse/dependence within 6 months;&#xD;
&#xD;
          -  Neurological disease (Abnormal PET-CT, MRI, EEG);&#xD;
&#xD;
          -  Contraindications of MRI-examination, e.g. implanted cardiac pacemaker/ heart&#xD;
             defibrillator;&#xD;
&#xD;
          -  Contraindications of stereotactic intervention, e.g. increased bleeding disposition,&#xD;
             cerebrovascular diseases;&#xD;
&#xD;
          -  Serious and unstable organic diseases (e.g. unstable coronal heart disease);&#xD;
&#xD;
          -  HIV positive;&#xD;
&#xD;
          -  Pregnancy and/or lactation;&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Shanghai Ruijin Hospital Functional Neurosurgery</name>
      <address>
        <city>Shanghai</city>
        <state>Shanghai</state>
        <zip>200025</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Shanghai Ruijin Hospital Functional Neurosurgery</name>
      <address>
        <city>Shanghai</city>
        <state>Shanghai</state>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <reference>
    <citation>Sartorius A, Kiening KL, Kirsch P, von Gall CC, Haberkorn U, Unterberg AW, Henn FA, Meyer-Lindenberg A. Remission of major depression under deep brain stimulation of the lateral habenula in a therapy-refractory patient. Biol Psychiatry. 2010 Jan 15;67(2):e9-e11. doi: 10.1016/j.biopsych.2009.08.027. No abstract available.</citation>
    <PMID>19846068</PMID>
  </reference>
  <reference>
    <citation>Kiening K, Sartorius A. A new translational target for deep brain stimulation to treat depression. EMBO Mol Med. 2013 Aug;5(8):1151-3. doi: 10.1002/emmm.201302947. Epub 2013 Jul 4. No abstract available.</citation>
    <PMID>23828711</PMID>
  </reference>
  <reference>
    <citation>Fakhoury M. The habenula in psychiatric disorders: More than three decades of translational investigation. Neurosci Biobehav Rev. 2017 Dec;83:721-735. doi: 10.1016/j.neubiorev.2017.02.010. Epub 2017 Feb 13.</citation>
    <PMID>28223096</PMID>
  </reference>
  <reference>
    <citation>Proulx CD, Hikosaka O, Malinow R. Reward processing by the lateral habenula in normal and depressive behaviors. Nat Neurosci. 2014 Sep;17(9):1146-52. doi: 10.1038/nn.3779.</citation>
    <PMID>25157511</PMID>
  </reference>
  <reference>
    <citation>Bergfeld IO, Mantione M, Hoogendoorn ML, Ruhe HG, Notten P, van Laarhoven J, Visser I, Figee M, de Kwaasteniet BP, Horst F, Schene AH, van den Munckhof P, Beute G, Schuurman R, Denys D. Deep Brain Stimulation of the Ventral Anterior Limb of the Internal Capsule for Treatment-Resistant Depression: A Randomized Clinical Trial. JAMA Psychiatry. 2016 May 1;73(5):456-64. doi: 10.1001/jamapsychiatry.2016.0152.</citation>
    <PMID>27049915</PMID>
  </reference>
  <reference>
    <citation>Li D, Zhang C, Gault J, Wang W, Liu J, Shao M, Zhao Y, Zeljic K, Gao G, Sun B. Remotely Programmed Deep Brain Stimulation of the Bilateral Subthalamic Nucleus for the Treatment of Primary Parkinson Disease: A Randomized Controlled Trial Investigating the Safety and Efficacy of a Novel Deep Brain Stimulation System. Stereotact Funct Neurosurg. 2017;95(3):174-182. doi: 10.1159/000475765. Epub 2017 Jun 2.</citation>
    <PMID>28571034</PMID>
  </reference>
  <reference>
    <citation>Zhang C, Li D, Zeljic K, Tan H, Ning Y, Sun B. A Remote and Wireless Deep Brain Stimulation Programming System. Neuromodulation. 2016 Jun;19(4):437-9. doi: 10.1111/ner.12448. No abstract available.</citation>
    <PMID>27321195</PMID>
  </reference>
  <verification_date>November 2019</verification_date>
  <study_first_submitted>August 16, 2017</study_first_submitted>
  <study_first_submitted_qc>August 16, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 18, 2017</study_first_posted>
  <last_update_submitted>November 26, 2019</last_update_submitted>
  <last_update_submitted_qc>November 26, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">November 29, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Ruijin Hospital</investigator_affiliation>
    <investigator_full_name>Bomin Sun</investigator_full_name>
    <investigator_title>Director of the Department of Functional Neurosurgery</investigator_title>
  </responsible_party>
  <keyword>Bilateral Habeluna</keyword>
  <keyword>Remote Deep Brain Stimulation</keyword>
  <keyword>Treatment Resistant Major Depressive Disorder</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>
    <mesh_term>Depressive Disorder, Major</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/NCT03254017
org study id: Habenula DBS
nct id: NCT03254017
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
The habenula(Hb) is an epithalamic structure located at the center of the dorsal diencephalic
      conduction system, a pathway involved in linking forebrain to midbrain regions. An increasing
      number of studies indicates that that overactivity in the lateral habeluna(LHb) is present
      during depressed states, where it could drive the changes in midbrain activity linked to
      depression. Deep brain stimulation(DBS) of the major afferent bundle (i.e., stria medullaris
      thalami) of the LHb can treat treatment-resistant major depression(TRD). There is no clinical
      case of directly stimulating habeluna for treatment TRD. This research will investigate
      effectiveness bilateral DBS to habenula for patients with TRD.

      Programming is a crucial aspect of DBS which directly influences its therapeutic efficacy.
      Researchers need to ascertain optimum stimulation parameters to help patients achieve optimal
      control of clinical symptoms. Remote programming of DBS can markedly improve patient
      convenience, minimize risk of infection and total treatment time and lead to an overall
      benefit for doctors and patients alike. This research will also investigate safety and
      benefit of remote programming of DBS.
allocation: N/A
intervention model: Single Group Assignment
intervention model description: all subjects will receive bilateral surgical implantation of DBS system.
primary purpose: Treatment
masking: None (Open Label)
measure: Change in the Montgomery-Asberg Depression Rating Scale
time frame: Baseline (preoperative),Biweekly after onset of the DBS system,3 months,6 months, 9 months, 12 months
measure: Change in the Hamilton Depression Scale
time frame: Baseline（preoperative）,3 months, 6 months,9 months, 12months
measure: Change in the Hamilton Anxiety Scale
time frame: Baseline（preoperative）,3 months, 6 months,9 months, 12months
measure: Change in the Quality of Life Assessment (SF-36)
time frame: Baseline（preoperative）,3 months, 6 months,9 months, 12 months
measure: Neuropsychological measures(Scores of cogstate battery)
time frame: Baseline（preoperative）,6 months,12 months
measure: Change in the Hamilton Anxiety Scale
time frame: Baseline（preoperative）,3 months, 6 months,9 months, 12 months
measure: Change in the WHO-BREF
time frame: Baseline（preoperative）,3 months,6 months,9 months, 12 months
measure: Change in Young Manic Rating Scale
time frame: Baseline (preoperative),Biweekly after onset of the DBS system,3 months,6 months, 9 months, 12 months
measure: Chang in Pittsburgh Sleep Quality Index
time frame: Baseline（preoperative）,3 months,6 months,9 months, 12 months
arm group label: Experimental Deep Brain Stimulation
arm group type: Experimental
description: Device：Suzhou Sceneray® DBS system
intervention type: Procedure
intervention name: Bilateral surgical implantation of DBS system to Habeluna
description: The SceneRay DBS device utilized in the present study is a double-channel device designed and manufactured by Suzhou Scene-Ray Medical Co., Ltd. The DBS system includes a dual-channel neurostimulator kit, lead kit, extension kit, clinician-operated wireless programmer, test stimulator, and patient controller. The lead (diameter =1.27 mm) contains four stimulating contacts made of platinumiridium alloy. The length of each contact is 1.5 mm, and interval spaces are 0.5 mm. This device shares the same basic principles utilized by Medtronic products, with unique wireless programming and electrode fixing designs. The amplitude (0-10 V), pulse width (60-960 ms), and frequency (1-1,600 Hz) can be programmed, and different frequencies may be utilized in the left and right hemispheres using this type of dual-channel IPG.
arm group label: Experimental Deep Brain Stimulation
intervention type: Other
intervention name: Follow-up Period
description: The researchers will remotely program the DBS biweekly after opening the stimulator and face to face test the patients' cognitive function every half year. Montgomery-Asberg Depression Rating Scale will be tested biweekly until the Programmed parameter has stable therapeutic efficacy and then tested after 3 months, 6 months, 9 months and 12 months.The other neuropsychological scales will be test on 3 months, 6 months, 9 months and 12 months.
arm group label: Experimental Deep Brain Stimulation
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: No
facility: 
facility: 
country: China
citation: Sartorius A, Kiening KL, Kirsch P, von Gall CC, Haberkorn U, Unterberg AW, Henn FA, Meyer-Lindenberg A. Remission of major depression under deep brain stimulation of the lateral habenula in a therapy-refractory patient. Biol Psychiatry. 2010 Jan 15;67(2):e9-e11. doi: 10.1016/j.biopsych.2009.08.027. No abstract available.
PMID: 19846068
citation: Kiening K, Sartorius A. A new translational target for deep brain stimulation to treat depression. EMBO Mol Med. 2013 Aug;5(8):1151-3. doi: 10.1002/emmm.201302947. Epub 2013 Jul 4. No abstract available.
PMID: 23828711
citation: Fakhoury M. The habenula in psychiatric disorders: More than three decades of translational investigation. Neurosci Biobehav Rev. 2017 Dec;83:721-735. doi: 10.1016/j.neubiorev.2017.02.010. Epub 2017 Feb 13.
PMID: 28223096
citation: Proulx CD, Hikosaka O, Malinow R. Reward processing by the lateral habenula in normal and depressive behaviors. Nat Neurosci. 2014 Sep;17(9):1146-52. doi: 10.1038/nn.3779.
PMID: 25157511
citation: Bergfeld IO, Mantione M, Hoogendoorn ML, Ruhe HG, Notten P, van Laarhoven J, Visser I, Figee M, de Kwaasteniet BP, Horst F, Schene AH, van den Munckhof P, Beute G, Schuurman R, Denys D. Deep Brain Stimulation of the Ventral Anterior Limb of the Internal Capsule for Treatment-Resistant Depression: A Randomized Clinical Trial. JAMA Psychiatry. 2016 May 1;73(5):456-64. doi: 10.1001/jamapsychiatry.2016.0152.
PMID: 27049915
citation: Li D, Zhang C, Gault J, Wang W, Liu J, Shao M, Zhao Y, Zeljic K, Gao G, Sun B. Remotely Programmed Deep Brain Stimulation of the Bilateral Subthalamic Nucleus for the Treatment of Primary Parkinson Disease: A Randomized Controlled Trial Investigating the Safety and Efficacy of a Novel Deep Brain Stimulation System. Stereotact Funct Neurosurg. 2017;95(3):174-182. doi: 10.1159/000475765. Epub 2017 Jun 2.
PMID: 28571034
citation: Zhang C, Li D, Zeljic K, Tan H, Ning Y, Sun B. A Remote and Wireless Deep Brain Stimulation Programming System. Neuromodulation. 2016 Jun;19(4):437-9. doi: 10.1111/ner.12448. No abstract available.
PMID: 27321195
responsible party type: Principal Investigator
investigator affiliation: Ruijin Hospital
investigator full name: Bomin Sun
investigator title: Director of the Department of Functional Neurosurgery
mesh term: Depression
mesh term: Depressive Disorder
mesh term: Depressive Disorder, Major