<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/NCT04436952</url>
  </required_header>
  <id_info>
    <org_study_id>ENV-OCD-2020-01</org_study_id>
    <nct_id>NCT04436952</nct_id>
  </id_info>
  <brief_title>Is There a New Gold Standard for the Treatment of Obsessive-Compulsive Disorder?</brief_title>
  <official_title>An Open Label Study to Compare and Evaluate the Efficacy of the Deep Transcranial Magnetic Stimulation With and Without Exposure and Response Prevention (ERP) to Repetitive Transcranial Magnetic Stimulation With and Without ERP to ERP.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Alberta</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Alberta</source>
  <oversight_info>
    <has_dmc>No</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>
      Obsessive Compulsive Disorder is a highly debilitating condition with a lifetime prevalence&#xD;
      of 2%-3%, and a notable percentage of patients (40-60%) have a partial or no response to&#xD;
      medications. The present gold standard for the treatment of OCD is medications (Selective&#xD;
      serotonin reuptake inhibitors (SSRIs) / Clomipramine) + Exposure and Response Prevention&#xD;
      (ERP). There is a significant need for alternative novel methods of treatment. One of the&#xD;
      novel methods of treating OCD is using magnetic stimulation which has already been&#xD;
      successfully used in the treatment of depression. Treating OCD is difficult with regular&#xD;
      superficial repetitive Transcranial Magnetic Stimulation (rTMS) hence the need for coils that&#xD;
      targets deeper structures. Thus, we are comparing the efficacy of the two different coils&#xD;
      from two different manufacturers plus using ERP in combination with the different coils.&#xD;
&#xD;
        1. Deep Transcranial Magnetic Stimulation (DTMS) using BrainsWay H7 coil targets deeper&#xD;
           structures such as medial prefrontal cortex. The H7 coil has already shown clear&#xD;
           evidence in treating patients with OCD and has been approved by the FDA for clinical&#xD;
           use.&#xD;
&#xD;
        2. Repetitive Transcranial Magnetic Stimulation (rTMS) using MagVenture Cool D-B coil could&#xD;
           also target the medial prefrontal cortex. Hence it might also be equally effective as&#xD;
           the BrainsWay H7 coil in treating patients with OCD.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      i. Purpose&#xD;
&#xD;
      a) The purpose of this study is to compare and evaluate the efficacy of repetitive&#xD;
      Transcranial Magnetic Stimulation (rTMS) by MagVenture and Deep Transcranial Magnetic&#xD;
      Stimulation (DTMS) by BrainsWay with and without the combination of active Exposure and&#xD;
      Response Prevention (ERP) for the treatment of patients with OCD.&#xD;
&#xD;
      ii. Hypothesis a) We hypothesize that the combination of TMS + active ERP will have a&#xD;
      superior efficacy in the treatment of OCD. We also hypothesize that MagVenture cool D-B80&#xD;
      coil will be as effective as BrainsWay H7 coil in treating patients with OCD.&#xD;
&#xD;
      iii. Justification&#xD;
&#xD;
        1. The Prospective Multicenter Randomized Double-Blind Placebo-Controlled Trial by Carmi et&#xD;
           al. (2019) had shown significant improvement in OCD symptoms by using the H7 coil and&#xD;
           provocation of OCD symptoms before and during treatment.&#xD;
&#xD;
        2. The study by Dunlop et al. (2016) has shown reduction in OCD symptom severity by using&#xD;
           the Cool D-B80 Coil without provocation.&#xD;
&#xD;
        3. There have been no head to head studies comparing the BrainsWay H7 coil and MagVenture&#xD;
           Cool D-B80 coil using provocation methods for both coils.&#xD;
&#xD;
        4. Also there have been no head to head studies comparing the gold standard treatment of&#xD;
           medications + active ERP with medications + active ERP + TMS and medications + TMS.&#xD;
&#xD;
      iv. Objectives&#xD;
&#xD;
      a) The aim of the study is to evaluate and compare the efficacy of DTMS treatment and the&#xD;
      rTMS treatment with and without the combination of active ERP in patients suffering from OCD,&#xD;
      in conjunction with medications approved for OCD treatment.&#xD;
&#xD;
      v. Research Method/Procedure&#xD;
&#xD;
        1. Recruit 100 patients suffering from OCD who have been treated and currently on at least&#xD;
           one SSRIs, SNRIs, clomipramine and at least one trial of CBT (Exposure and Response&#xD;
           Prevention) had an inadequate response.&#xD;
&#xD;
        2. Make a personalized provocation for each patient and using them during treatment&#xD;
&#xD;
        3. The trial will consist of 3 phases:&#xD;
&#xD;
             1. Pre-study screening and baseline assessment;&#xD;
&#xD;
             2. Treatment trial period (8 weeks); and&#xD;
&#xD;
             3. Follow-up (12 weeks).&#xD;
&#xD;
        4. Clinical severity rating scales will be taken every other week and include: (Brief&#xD;
           Obsessive-Compulsive Scale (BOCS), Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) ,&#xD;
           Beck's Depression Inventory (BDI), Clinical Global Impression Severity (CGI-S) and&#xD;
           Clinical Global Impression Improvement (CGI-I). Safety evaluations will include adverse&#xD;
           event monitoring, vital signs, and cognitive changes (Mini-Mental State Exam (MMSE)).&#xD;
           All measures will be taken before treatment administration.&#xD;
&#xD;
        5. Pre-Study Screening and Baseline Assessment&#xD;
&#xD;
             1. Potential Patients will be given complete information describing the study&#xD;
                treatment and their role in the trial, and they will be encouraged to ask any&#xD;
                questions regarding the trial. The risks and requirements of this clinical research&#xD;
                trial will be explained to each potential patient. Those volunteering to take part&#xD;
                will read and sign the Informed Consent Form for participation in the clinical&#xD;
                research trial before any trial-related procedures are performed.&#xD;
&#xD;
             2. Upon obtaining the signed informed consent, inclusion and exclusion criteria will&#xD;
                be reviewed to verify the patient's eligibility.&#xD;
&#xD;
             3. Baseline data are defined as the data generated during the baseline visit before&#xD;
                the first treatment Session.&#xD;
&#xD;
        6. After the patients has been admitted into the study, they will be asked to undergo a&#xD;
           fMRI and then randomly organized based on age and symptom severity into the 5 different&#xD;
           groups.&#xD;
&#xD;
        7. Comparing 5 groups of patients with OCD 1) Group 1 - 20 patients undergoing DTMS&#xD;
           treatment using the H7 coil 2) Group 2 - 20 patients undergoing rTMS treatment using the&#xD;
           cool D-B80 coil 3) Group 3 - 20 patients undergoing DTMS treatment using the H7 coil +&#xD;
           ERP 4) Group 4 - 20 patients undergoing rTMS treatment using the cool D-B80 coil + ERP&#xD;
           5) Group 5 - 20 patients undergoing ERP only&#xD;
&#xD;
        8. Treatment Trial period&#xD;
&#xD;
           1) During the treatment phase the patients will either receive&#xD;
&#xD;
           Group 1 - medial prefrontal cortex (mPFC) DTMS 5 days a week for 8 consecutive weeks =&#xD;
           40 Sessions 20 Hz at 100% MT, 2 s on 20 s off intertrain interval, 50 trains, 2000&#xD;
           stimuli per session.&#xD;
&#xD;
           TMS will be done at active state by provocation&#xD;
&#xD;
           Group 2 - dorsomedial prefrontal cortex (DMPFC) rTMS 5 days a week for 8 consecutive&#xD;
           weeks = 40 sessions 10 Hz at 120% MT, 5 s on 10 s off intertrain interval, 60 trains,&#xD;
           First 3000 pulses to the left DMPFC then 3000 pulses to the right DMPFC. TMS will be&#xD;
           done at active state by provocation&#xD;
&#xD;
           Group 3 - medial prefrontal cortex (mPFC) DTMS + ERP 5 days a week for 8 consecutive&#xD;
           weeks = 40 sessions 20 Hz at 100% MT, 2 s on 20 s off intertrain interval, 50 trains,&#xD;
           2000 stimuli per session. TMS will be done at active state by provocation The ERP will&#xD;
           be administered for 2 hours on week 1 and week 8 and for 1 hour on Weeks 2 to 7 for a&#xD;
           total of 10 hours.&#xD;
&#xD;
           Group 4 - dorsomedial prefrontal cortex (DMPFC) rTMS +ERP 5 days a week for 8&#xD;
           consecutive weeks = 40 sessions 10 Hz at 120% MT, 5 s on 10 s off intertrain interval,&#xD;
           60 trains, First 3000 pulses to the left DMPFC then 3000 pulses to the right DMPFC. TMS&#xD;
           will be done at active state by provocation The ERP will be administered for 2 hours on&#xD;
           week 1 and week 8 and for 1 hour on Weeks 2 to 7 for a total of 10 hours.&#xD;
&#xD;
           Group 5 - ERP The ERP will be conducted for 2 hours on week 1 and week 8 and for 1 hour&#xD;
           on Weeks 2 to 7 for a total of 10 hours.&#xD;
&#xD;
        9. Prior to initiation and during each treatment of TMS, OCD symptoms will be provoked for&#xD;
           each patient in an individual manner to activate the relevant brain circuitry. Targeted&#xD;
           questions will be designed for each patient using external, internal or a combination of&#xD;
           provocations and the degree of provocation on a Visual Analog Scale will be recorded.&#xD;
           These may require adjustment as the patient improves.&#xD;
&#xD;
       10. Study evaluations will be performed every week at the beginning of the next treatment&#xD;
           week (from week 2), prior to the first or second (preferably second) treatment session&#xD;
           of that week. Procedures to be performed at the 8-week visit will also be performed in&#xD;
           case of Early Discontinuation of the study.&#xD;
&#xD;
       11. Follow up period 1) All patients will be followed up at week 12. vi. Plan for Data&#xD;
           Analysis&#xD;
&#xD;
        1. Primary Efficacy Variable&#xD;
&#xD;
           - The primary outcome measure is the BOCS and YBOCS severity rating scale. The primary&#xD;
           efficacy endpoint is the change in BOCS and YBOCS severity score from baseline to the&#xD;
           8-week visit.&#xD;
&#xD;
        2. Secondary Efficacy Variables&#xD;
&#xD;
           - Change from baseline to the 8-week visit in the Clinical Global Impression - Severity&#xD;
           (CGI-S) and Improvement (CGI-I) scores.&#xD;
&#xD;
           - Change from baseline to the 12-week visit in the BOCS and YBOCS severity score.&#xD;
&#xD;
           - Change from baseline to the 12-week visit in the Clinical Global Impression - Severity&#xD;
           (CGI-S) and Improvement (CGI-I) scores.&#xD;
&#xD;
        3. Exploratory Efficacy Variables - Change from baseline to the 8 week and 12 weeks visit&#xD;
           in the Beck's Depression Inventory score.&#xD;
&#xD;
             -  fMRI changes before and after treatment and using fMRI to predict future response&#xD;
                to TMS treatment (to identify responders and non-responders)&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Withdrawn</overall_status>
  <why_stopped>
    Change in Protocol&#xD;
  </why_stopped>
  <start_date type="Anticipated">July 2020</start_date>
  <completion_date type="Anticipated">July 2022</completion_date>
  <primary_completion_date type="Anticipated">February 2021</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <intervention_model_description>Group 1 - 20 patients undergoing DTMS treatment using the H7 coil&#xD;
Group 2 - 20 patients undergoing rTMS treatment using the cool D-B80 coil&#xD;
Group 3 - 20 patients undergoing DTMS treatment using the H7 coil + ERP&#xD;
Group 4 - 20 patients undergoing rTMS treatment using the cool D-B80 coil + ERP&#xD;
Group 5 - 20 patients undergoing ERP only</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Reduction in the severity of OCD symptoms</measure>
    <time_frame>8 weeks</time_frame>
    <description>- The primary outcome measure is the BOCS and YBOCS severity rating scale. The primary efficacy endpoint is the change in BOCS and YBOCS severity score from baseline to the 8-week visit.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Clinical Global Impression - Severity (CGI-S) and Improvement (CGI-I) scores.</measure>
    <time_frame>8-12 weeks</time_frame>
    <description>Change from baseline to the 8-week visit in the Clinical Global Impression - Severity (CGI-S) and Improvement (CGI-I) scores.&#xD;
Change from baseline to the 12-week visit in the BOCS and YBOCS severity score. Change from baseline to the 12-week visit in the Clinical Global Impression - Severity (CGI-S) and Improvement (CGI-I) scores.</description>
  </secondary_outcome>
  <number_of_arms>5</number_of_arms>
  <enrollment type="Actual">0</enrollment>
  <condition>Obsessive-Compulsive Disorder</condition>
  <arm_group>
    <arm_group_label>H7 coil only</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>patients undergoing DTMS treatment using the H7 coil</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cool D-B80 coil only</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>20 patients undergoing rTMS treatment using the cool D-B80 coil</description>
  </arm_group>
  <arm_group>
    <arm_group_label>DTMS treatment using the H7 coil + ERP</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>20 patients undergoing DTMS treatment using the H7 coil + ERP</description>
  </arm_group>
  <arm_group>
    <arm_group_label>rTMS treatment using the cool D-B80 coil + ERP</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>20 patients undergoing rTMS treatment using the cool D-B80 coil + ERP</description>
  </arm_group>
  <arm_group>
    <arm_group_label>ERP only</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>20 patients undergoing ERP only</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>H7 coil</intervention_name>
    <description>The H7 coil arm will receive a medial prefrontal cortex (mPFC) DTMS 5 days a week for 8 consecutive weeks = 40 Sessions 20 Hz at 100% MT, 2 s on 20 s off intertrain interval, 50 trains, 2000 stimuli per session.</description>
    <arm_group_label>DTMS treatment using the H7 coil + ERP</arm_group_label>
    <arm_group_label>H7 coil only</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Cool D-B80</intervention_name>
    <description>The Cool D-B80 arm will receive dorsomedial prefrontal cortex (DMPFC) rTMS 5 days a week for 8 consecutive weeks = 40 sessions 10 Hz at 120% MT, 5 s on 10 s off intertrain interval, 60 trains, First 3000 pulses to the left DMPFC then 3000 pulses to the right DMPFC. TMS will be done at active state by provocation</description>
    <arm_group_label>Cool D-B80 coil only</arm_group_label>
    <arm_group_label>rTMS treatment using the cool D-B80 coil + ERP</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Behavioral</intervention_type>
    <intervention_name>Exposure Response Prevention (ERP)</intervention_name>
    <description>The ERP will be conducted for 2 hours on week 1 and week 8 and for 1 hour on Weeks 2 to 7 for a total of 10 hours</description>
    <arm_group_label>DTMS treatment using the H7 coil + ERP</arm_group_label>
    <arm_group_label>ERP only</arm_group_label>
    <arm_group_label>rTMS treatment using the cool D-B80 coil + ERP</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        i. Outpatients ii. Men and women 18-70 years of age. iii. Patients diagnosed as suffering&#xD;
        from OCD according to the BOCS and YBOCs. iv. Patients had an inadequate/intolerable&#xD;
        response to SSRI, CBT (Exposure and Response Prevention) or both.&#xD;
&#xD;
        v. Patient is capable and willing to provide informed consent, and their guardians is&#xD;
        capable of providing informed consent.&#xD;
&#xD;
        vi. Patient is able to adhere to the treatment schedule.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        i. Present suicidal risk is significant as assessed during the investigator's mental status&#xD;
        exam and psychiatric interview.&#xD;
&#xD;
        ii. Patient has a history of epilepsy or seizure (EXCEPT those therapeutically induced by&#xD;
        ECT) or history of such in first-degree relatives.&#xD;
&#xD;
        iii. Patient has an increased risk of seizure for any reason, including prior diagnosis of&#xD;
        increased intracranial pressure, or history of significant head trauma with loss of&#xD;
        consciousness for greater than or equal to 5 minutes.&#xD;
&#xD;
        iv. Patient has a history of head injury necessitating cranial surgery or prolonged coma.&#xD;
&#xD;
        v. Patient has ferromagnetic material in the head including the eyes and ears (outside the&#xD;
        mouth) and body.&#xD;
&#xD;
        vi. Patient has a history of significant hearing loss. vii. Patients with significant&#xD;
        neurological disorder or insult including, but not limited to:&#xD;
&#xD;
          1. Any condition likely to be associated with increased intracranial pressure&#xD;
&#xD;
          2. Space occupying brain lesion&#xD;
&#xD;
          3. History of cerebrovascular accident&#xD;
&#xD;
          4. Transient ischemic attack within two years&#xD;
&#xD;
          5. Cerebral aneurysm&#xD;
&#xD;
          6. Dementia&#xD;
&#xD;
          7. Parkinson's disease&#xD;
&#xD;
          8. Huntington's chorea&#xD;
&#xD;
          9. Multiple sclerosis&#xD;
&#xD;
         10. Mini Mental State Exam score of less than or equal to 24 (for adult participants)&#xD;
             viii. Patient has a history of substance abuse including alcohol use disorder within&#xD;
             the past 6 months (except nicotine and caffeine).&#xD;
&#xD;
        ix. Inadequate communication with the patient. x. Patient is currently participating in&#xD;
        another clinical study or enrolled in another clinical study within 30 days prior to this&#xD;
        study.&#xD;
&#xD;
        xi. Patients who suffer from an unstable physical, systemic and metabolic disorder such as&#xD;
        unstable blood pressure or acute, unstable cardiac disease.&#xD;
&#xD;
        xii. Women who are pregnant or with suspected pregnancy&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>70 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Karthikeyan Ganapathy, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Alberta Health Services/ Envision Mind Care</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Envision Mind Care</name>
      <address>
        <city>Edmonton</city>
        <state>Alberta</state>
        <zip>T6W 2Z8</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Canada</country>
  </location_countries>
  <verification_date>June 2020</verification_date>
  <study_first_submitted>May 23, 2020</study_first_submitted>
  <study_first_submitted_qc>June 16, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 18, 2020</study_first_posted>
  <last_update_submitted>July 14, 2022</last_update_submitted>
  <last_update_submitted_qc>July 14, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">July 18, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Obsessive Compulsive Disorder</keyword>
  <keyword>Transcranial Magnetic Stimulation</keyword>
  <keyword>Exposure and Response Prevention</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Compulsive Personality Disorder</mesh_term>
    <mesh_term>Obsessive-Compulsive Disorder</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</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/NCT04436952
org study id: ENV-OCD-2020-01
nct id: NCT04436952
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: Yes
is us export: Yes
Obsessive Compulsive Disorder is a highly debilitating condition with a lifetime prevalence
      of 2%-3%, and a notable percentage of patients (40-60%) have a partial or no response to
      medications. The present gold standard for the treatment of OCD is medications (Selective
      serotonin reuptake inhibitors (SSRIs) / Clomipramine) + Exposure and Response Prevention
      (ERP). There is a significant need for alternative novel methods of treatment. One of the
      novel methods of treating OCD is using magnetic stimulation which has already been
      successfully used in the treatment of depression. Treating OCD is difficult with regular
      superficial repetitive Transcranial Magnetic Stimulation (rTMS) hence the need for coils that
      targets deeper structures. Thus, we are comparing the efficacy of the two different coils
      from two different manufacturers plus using ERP in combination with the different coils.

        1. Deep Transcranial Magnetic Stimulation (DTMS) using BrainsWay H7 coil targets deeper
           structures such as medial prefrontal cortex. The H7 coil has already shown clear
           evidence in treating patients with OCD and has been approved by the FDA for clinical
           use.

        2. Repetitive Transcranial Magnetic Stimulation (rTMS) using MagVenture Cool D-B coil could
           also target the medial prefrontal cortex. Hence it might also be equally effective as
           the BrainsWay H7 coil in treating patients with OCD.
i. Purpose

      a) The purpose of this study is to compare and evaluate the efficacy of repetitive
      Transcranial Magnetic Stimulation (rTMS) by MagVenture and Deep Transcranial Magnetic
      Stimulation (DTMS) by BrainsWay with and without the combination of active Exposure and
      Response Prevention (ERP) for the treatment of patients with OCD.

      ii. Hypothesis a) We hypothesize that the combination of TMS + active ERP will have a
      superior efficacy in the treatment of OCD. We also hypothesize that MagVenture cool D-B80
      coil will be as effective as BrainsWay H7 coil in treating patients with OCD.

      iii. Justification

        1. The Prospective Multicenter Randomized Double-Blind Placebo-Controlled Trial by Carmi et
           al. (2019) had shown significant improvement in OCD symptoms by using the H7 coil and
           provocation of OCD symptoms before and during treatment.

        2. The study by Dunlop et al. (2016) has shown reduction in OCD symptom severity by using
           the Cool D-B80 Coil without provocation.

        3. There have been no head to head studies comparing the BrainsWay H7 coil and MagVenture
           Cool D-B80 coil using provocation methods for both coils.

        4. Also there have been no head to head studies comparing the gold standard treatment of
           medications + active ERP with medications + active ERP + TMS and medications + TMS.

      iv. Objectives

      a) The aim of the study is to evaluate and compare the efficacy of DTMS treatment and the
      rTMS treatment with and without the combination of active ERP in patients suffering from OCD,
      in conjunction with medications approved for OCD treatment.

      v. Research Method/Procedure

        1. Recruit 100 patients suffering from OCD who have been treated and currently on at least
           one SSRIs, SNRIs, clomipramine and at least one trial of CBT (Exposure and Response
           Prevention) had an inadequate response.

        2. Make a personalized provocation for each patient and using them during treatment

        3. The trial will consist of 3 phases:

             1. Pre-study screening and baseline assessment;

             2. Treatment trial period (8 weeks); and

             3. Follow-up (12 weeks).

        4. Clinical severity rating scales will be taken every other week and include: (Brief
           Obsessive-Compulsive Scale (BOCS), Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) ,
           Beck's Depression Inventory (BDI), Clinical Global Impression Severity (CGI-S) and
           Clinical Global Impression Improvement (CGI-I). Safety evaluations will include adverse
           event monitoring, vital signs, and cognitive changes (Mini-Mental State Exam (MMSE)).
           All measures will be taken before treatment administration.

        5. Pre-Study Screening and Baseline Assessment

             1. Potential Patients will be given complete information describing the study
                treatment and their role in the trial, and they will be encouraged to ask any
                questions regarding the trial. The risks and requirements of this clinical research
                trial will be explained to each potential patient. Those volunteering to take part
                will read and sign the Informed Consent Form for participation in the clinical
                research trial before any trial-related procedures are performed.

             2. Upon obtaining the signed informed consent, inclusion and exclusion criteria will
                be reviewed to verify the patient's eligibility.

             3. Baseline data are defined as the data generated during the baseline visit before
                the first treatment Session.

        6. After the patients has been admitted into the study, they will be asked to undergo a
           fMRI and then randomly organized based on age and symptom severity into the 5 different
           groups.

        7. Comparing 5 groups of patients with OCD 1) Group 1 - 20 patients undergoing DTMS
           treatment using the H7 coil 2) Group 2 - 20 patients undergoing rTMS treatment using the
           cool D-B80 coil 3) Group 3 - 20 patients undergoing DTMS treatment using the H7 coil +
           ERP 4) Group 4 - 20 patients undergoing rTMS treatment using the cool D-B80 coil + ERP
           5) Group 5 - 20 patients undergoing ERP only

        8. Treatment Trial period

           1) During the treatment phase the patients will either receive

           Group 1 - medial prefrontal cortex (mPFC) DTMS 5 days a week for 8 consecutive weeks =
           40 Sessions 20 Hz at 100% MT, 2 s on 20 s off intertrain interval, 50 trains, 2000
           stimuli per session.

           TMS will be done at active state by provocation

           Group 2 - dorsomedial prefrontal cortex (DMPFC) rTMS 5 days a week for 8 consecutive
           weeks = 40 sessions 10 Hz at 120% MT, 5 s on 10 s off intertrain interval, 60 trains,
           First 3000 pulses to the left DMPFC then 3000 pulses to the right DMPFC. TMS will be
           done at active state by provocation

           Group 3 - medial prefrontal cortex (mPFC) DTMS + ERP 5 days a week for 8 consecutive
           weeks = 40 sessions 20 Hz at 100% MT, 2 s on 20 s off intertrain interval, 50 trains,
           2000 stimuli per session. TMS will be done at active state by provocation The ERP will
           be administered for 2 hours on week 1 and week 8 and for 1 hour on Weeks 2 to 7 for a
           total of 10 hours.

           Group 4 - dorsomedial prefrontal cortex (DMPFC) rTMS +ERP 5 days a week for 8
           consecutive weeks = 40 sessions 10 Hz at 120% MT, 5 s on 10 s off intertrain interval,
           60 trains, First 3000 pulses to the left DMPFC then 3000 pulses to the right DMPFC. TMS
           will be done at active state by provocation The ERP will be administered for 2 hours on
           week 1 and week 8 and for 1 hour on Weeks 2 to 7 for a total of 10 hours.

           Group 5 - ERP The ERP will be conducted for 2 hours on week 1 and week 8 and for 1 hour
           on Weeks 2 to 7 for a total of 10 hours.

        9. Prior to initiation and during each treatment of TMS, OCD symptoms will be provoked for
           each patient in an individual manner to activate the relevant brain circuitry. Targeted
           questions will be designed for each patient using external, internal or a combination of
           provocations and the degree of provocation on a Visual Analog Scale will be recorded.
           These may require adjustment as the patient improves.

       10. Study evaluations will be performed every week at the beginning of the next treatment
           week (from week 2), prior to the first or second (preferably second) treatment session
           of that week. Procedures to be performed at the 8-week visit will also be performed in
           case of Early Discontinuation of the study.

       11. Follow up period 1) All patients will be followed up at week 12. vi. Plan for Data
           Analysis

        1. Primary Efficacy Variable

           - The primary outcome measure is the BOCS and YBOCS severity rating scale. The primary
           efficacy endpoint is the change in BOCS and YBOCS severity score from baseline to the
           8-week visit.

        2. Secondary Efficacy Variables

           - Change from baseline to the 8-week visit in the Clinical Global Impression - Severity
           (CGI-S) and Improvement (CGI-I) scores.

           - Change from baseline to the 12-week visit in the BOCS and YBOCS severity score.

           - Change from baseline to the 12-week visit in the Clinical Global Impression - Severity
           (CGI-S) and Improvement (CGI-I) scores.

        3. Exploratory Efficacy Variables - Change from baseline to the 8 week and 12 weeks visit
           in the Beck's Depression Inventory score.

             -  fMRI changes before and after treatment and using fMRI to predict future response
                to TMS treatment (to identify responders and non-responders)
allocation: Non-Randomized
intervention model: Parallel Assignment
intervention model description: Group 1 - 20 patients undergoing DTMS treatment using the H7 coil
Group 2 - 20 patients undergoing rTMS treatment using the cool D-B80 coil
Group 3 - 20 patients undergoing DTMS treatment using the H7 coil + ERP
Group 4 - 20 patients undergoing rTMS treatment using the cool D-B80 coil + ERP
Group 5 - 20 patients undergoing ERP only
primary purpose: Treatment
masking: None (Open Label)
measure: Reduction in the severity of OCD symptoms
time frame: 8 weeks
description: - The primary outcome measure is the BOCS and YBOCS severity rating scale. The primary efficacy endpoint is the change in BOCS and YBOCS severity score from baseline to the 8-week visit.
measure: Clinical Global Impression - Severity (CGI-S) and Improvement (CGI-I) scores.
time frame: 8-12 weeks
description: Change from baseline to the 8-week visit in the Clinical Global Impression - Severity (CGI-S) and Improvement (CGI-I) scores.
Change from baseline to the 12-week visit in the BOCS and YBOCS severity score. Change from baseline to the 12-week visit in the Clinical Global Impression - Severity (CGI-S) and Improvement (CGI-I) scores.
arm group label: H7 coil only
arm group type: Experimental
description: patients undergoing DTMS treatment using the H7 coil
arm group label: Cool D-B80 coil only
arm group type: Active Comparator
description: 20 patients undergoing rTMS treatment using the cool D-B80 coil
arm group label: DTMS treatment using the H7 coil + ERP
arm group type: Active Comparator
description: 20 patients undergoing DTMS treatment using the H7 coil + ERP
arm group label: rTMS treatment using the cool D-B80 coil + ERP
arm group type: Active Comparator
description: 20 patients undergoing rTMS treatment using the cool D-B80 coil + ERP
arm group label: ERP only
arm group type: Active Comparator
description: 20 patients undergoing ERP only
intervention type: Device
intervention name: H7 coil
description: The H7 coil arm will receive a medial prefrontal cortex (mPFC) DTMS 5 days a week for 8 consecutive weeks = 40 Sessions 20 Hz at 100% MT, 2 s on 20 s off intertrain interval, 50 trains, 2000 stimuli per session.
arm group label: DTMS treatment using the H7 coil + ERP
arm group label: H7 coil only
intervention type: Device
intervention name: Cool D-B80
description: The Cool D-B80 arm will receive dorsomedial prefrontal cortex (DMPFC) rTMS 5 days a week for 8 consecutive weeks = 40 sessions 10 Hz at 120% MT, 5 s on 10 s off intertrain interval, 60 trains, First 3000 pulses to the left DMPFC then 3000 pulses to the right DMPFC. TMS will be done at active state by provocation
arm group label: Cool D-B80 coil only
arm group label: rTMS treatment using the cool D-B80 coil + ERP
intervention type: Behavioral
intervention name: Exposure Response Prevention (ERP)
description: The ERP will be conducted for 2 hours on week 1 and week 8 and for 1 hour on Weeks 2 to 7 for a total of 10 hours
arm group label: DTMS treatment using the H7 coil + ERP
arm group label: ERP only
arm group label: rTMS treatment using the cool D-B80 coil + ERP
criteria: 
gender: All
minimum age: 18 Years
maximum age: 70 Years
healthy volunteers: No
last name: Karthikeyan Ganapathy, MD
role: Principal Investigator
affiliation: Alberta Health Services/ Envision Mind Care
facility: 
country: Canada
responsible party type: Sponsor
mesh term: Compulsive Personality Disorder
mesh term: Obsessive-Compulsive Disorder
sharing ipd: No