<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/NCT03753698</url>
  </required_header>
  <id_info>
    <org_study_id>EOC.NEUUR.1801</org_study_id>
    <nct_id>NCT03753698</nct_id>
  </id_info>
  <brief_title>Wireless, Implantable Tibial Nerve Stimulator System (eCoin™) for the Treatment of Refractory Lower Urinary Tract Symptoms in Patients With MS</brief_title>
  <official_title>A Prospective, Single Arm, Interventional, Self-controlled Pilot Study to Assess the Performance and Safety of the New Generation, Wireless, Implantable Tibial Nerve Stimulator System (eCoin™) for the Treatment of Refractory Lower Urinary Tract Symptoms in Patients With Multiple Sclerosis</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Chiara Zecca</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Ente Ospedaliero Cantonale, Bellinzona</source>
  <oversight_info>
    <has_dmc>No</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>
      Prevalence of lower urinary tract symptoms (LUTS) in patients with MS increases with disease&#xD;
      duration. Current management of urinary clinical symptoms in MS is mainly conservative. Its&#xD;
      long-term outcome is often poor because of the progressive disease course and the treatment&#xD;
      related side effects. Alternative therapeutic options are botulinum toxin injections,&#xD;
      electrical stimulation of dorsal penile/clitoral nerve, and sacral nerve modulation.&#xD;
      Posterior tibial nerve stimulation (PTNS) is a second minimally-invasive method of electrical&#xD;
      stimulation. Multiple benefits may derive from the development and validation of a dedicated&#xD;
      protocol of a new self-activated neuromodulation therapy, which may improve therapy&#xD;
      compliance/effectiveness, quality of life and social life in MS patients with refractory&#xD;
      LUTS. Furthermore, it may contribute to reduce outpatient visits, health costs and work&#xD;
      absenteeism.&#xD;
&#xD;
      To investigate the performance and safety of the medical device eCoin™ for the treatment of&#xD;
      refractory LUTS in patients with MS over a period of 6 months.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a prospective, interventional, single arm, self-controlled pilot study in patients&#xD;
      with multiple sclerosis and OAB symptoms with a 6-month treatment period of posterior tibial&#xD;
      nerve stimulation with the medical device eCoin.&#xD;
&#xD;
      It is a pilot study to explore the effectiveness and safety of using this device to treat MS&#xD;
      patients with OAB in daily clinical practice in. Based on feasibility considerations, we plan&#xD;
      to include approximately 20 patients.&#xD;
&#xD;
      It consists of:&#xD;
&#xD;
        1. wash-out period from PTNS treatment of at least 2 months;&#xD;
&#xD;
        2. baseline assessments;&#xD;
&#xD;
        3. implantation of eCoin;&#xD;
&#xD;
        4. system activation; and&#xD;
&#xD;
        5. treatment and follow-up visits for a 6-month period post implant activation. Seven&#xD;
           Visits are foreseen during the trial.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Withdrawn</overall_status>
  <why_stopped>
    Substantial amendment to be implemented using another device&#xD;
  </why_stopped>
  <start_date type="Anticipated">July 1, 2020</start_date>
  <completion_date type="Anticipated">December 31, 2022</completion_date>
  <primary_completion_date type="Anticipated">December 31, 2022</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>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change from baseline in bladder volume (mL)</measure>
    <time_frame>Baseline and Week 24</time_frame>
    <description>The patients will have their bladder filling volume measured during a urodynamic exam.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change from baseline of detrusor pressure amplitude (cmH2O)</measure>
    <time_frame>Baseline and Week 24</time_frame>
    <description>The patients will have their detrusor pressure measured during an urodynamic exam.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change from baseline of cystometric capacity (mL)</measure>
    <time_frame>Baseline and Week 24</time_frame>
    <description>The patients will have their cystometric capacity measured during an urodynamic exam.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from baseline of bladder compliance (mL/cmH2O)</measure>
    <time_frame>Baseline and Week 24</time_frame>
    <description>The patients will have their bladder compliance assessed during an urodynamic exam.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from baseline of maximum detrusor pressure (cmH20) during storage phase</measure>
    <time_frame>Baseline and Week 24</time_frame>
    <description>The patients will have their maximum detrusor pressure during storage phase measured during an urodynamic exam.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from baseline of maximum detrusor pressure (cmH20) during voiding phase</measure>
    <time_frame>Baseline and Week 24</time_frame>
    <description>The patients will have their maximum detrusor pressure during voiding phase measured during an urodynamic exam.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from baseline of voided urine volume (mL)</measure>
    <time_frame>Baseline and Week 24</time_frame>
    <description>The patients will have their voided urine volume measured during an urodynamic exam.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from baseline of maximum urine flow rate (mL/s)</measure>
    <time_frame>Baseline and Week 24</time_frame>
    <description>The patients will have the maximum urine flow rate measured during an urodynamic exam.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from baseline of post void residual urine (mL)</measure>
    <time_frame>Baseline and Week 24</time_frame>
    <description>The patients will have the post void residual urine measured during an urodynamic exam.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from baseline of pelvic floor electromyographic activity</measure>
    <time_frame>Baseline and Week 24</time_frame>
    <description>The patients will have presence or absence of pelvic floor activity recorded during an urodynamic exam.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from baseline of vesico-uretero-renal reflux</measure>
    <time_frame>Baseline and Week 24</time_frame>
    <description>The patients will have presence or absence of vesico-uretero-renal reflux assessed during an urodynamic exam.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from baseline to 4, 12, and 24 weeks of bladder voiding assessed by means of a 3-day voiding diary</measure>
    <time_frame>Baseline and Week 4, 12, 24</time_frame>
    <description>The patients will self-record their bladder voiding during three consecutive days at each time point including the number of voids/day, volume voided/void, number of leaks per day, degree of urgency prior to void (none, mild, moderate, severe, incontinence), number of self-catheterization needed through the day.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from baseline to 4, 12, and 24 weeks of overactive bladder symptoms scores using the short form of the overactive bladder questionnaire OAB-q</measure>
    <time_frame>Baseline, Week 4, 12, 24</time_frame>
    <description>The patients will rate their overactive bladder symptoms using the OAB-qSF questionnaire. It is self-administered and asks about how much a patients is bothered by selected bladder symptoms. It contains 6 questions about symptom severity and 13 on coping, sleeping, social life each to be rated on a 6-point scale (none of the time, a little of the time, some of the time, a good bit of the time, most of the time, all of the time). Symptom severity ranges from 6 (not bothered) to 36 (extremely bothered), impact on health related quality of life ranges from 13 (not bothered) to 78 (extremely bothered).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from baseline to 4, 12, and 24 weeks of MSQOL54 scores.</measure>
    <time_frame>Week -8, 4, 12, 24</time_frame>
    <description>The patients will assess their health related quality of life using the short form of the MSQOL 54 questionnaire. This is a self-administered multidimensional questionnaire on health-related quality of life with generic and multiple sclerosis specific questions on physical and mental health. The summary scores are derived from 12 subscales (physical function, physical role limitations, emotional role limitations, pain, emotional well-being, energy, health perceptions, social function, cognitive function, health distress, overall quality of life, sexual function). A low score indicates bad quality of life, a higher score improved quality of life (range 0-100).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Treatment satisfaction, as measured on a composite visual analogue scale (VAS) score ranging from 0-100</measure>
    <time_frame>Week 24</time_frame>
    <description>The patients will mark a point on a 100 mm long line with a pencil to indicate their treatment satisfaction. 0 (not satisfied at all), 100 (very satisfied).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of adverse events</measure>
    <time_frame>Week 0, 5, 12, 24</time_frame>
    <description>Number and proportion of patients experiencing device related adverse events during the study period will be recorded.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">0</enrollment>
  <condition>Multiple Sclerosis</condition>
  <arm_group>
    <arm_group_label>eCoin</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Neuromodulation of posterior tibial nerve</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>eCoin</intervention_name>
    <description>Implantation of device electrodes subcutaneous in lower tibia area;&#xD;
Stimulation of posterior tibial nerves:&#xD;
Regimen 1 (months 0-3): Six stimulation treatments per week, one stimulation per day, for duration of 30 minutes each Regimen 2 (months 3-6): Three stimulation treatments per week, one stimulation per day, for duration of 30 minutes each. Stimulation is activated by the patient.</description>
    <arm_group_label>eCoin</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Main Inclusion Criteria:&#xD;
&#xD;
          -  Diagnosis of MS according to MacDonald (2011);&#xD;
&#xD;
          -  Clinical stability over the past 6 months (no relapses or EDSS progression over the&#xD;
             last 6 months);&#xD;
&#xD;
          -  One or more of: urinary frequency greater than 8 times/24 hours, urinary urge&#xD;
             incontinence at least 2 episodes in 24 hours on 3-day voiding diary&#xD;
&#xD;
          -  Urodynamic diagnosis of detrusor over-activity (DOA) and / or detrusor-sphincter&#xD;
             dyssynergia (DSD);&#xD;
&#xD;
          -  Previous failure of conservative treatments (challenge over ≥6 months) i.e. lifestyle&#xD;
             modification-fluid consumption, behavioural modification, and pharmacological therapy&#xD;
             and stable OAB medications for at least 30 days or intolerance to pharmacological&#xD;
             therapy (side effect);&#xD;
&#xD;
          -  Positive response to ongoing PTNS treatment defined as ≥50% reduction in urinary&#xD;
             frequency, and/or ≥50% fewer incontinence episodes, or a return to normal voiding&#xD;
             frequency [&lt;8 voids/day], based on retrospective diary review;&#xD;
&#xD;
          -  Competent sphincter mechanism and normally functioning upper urinary tract;&#xD;
&#xD;
          -  Leg circumference in the range of 20-30 cm at implantation site;&#xD;
&#xD;
          -  Ability to comply with study requirements;&#xD;
&#xD;
          -  Having provided written informed consent&#xD;
&#xD;
        Main Exclusion Criteria:&#xD;
&#xD;
          -  Participation in another study with any investigational drug or device within the past&#xD;
             90 days;&#xD;
&#xD;
          -  Any metal implant in the area of eCoin implantation site;&#xD;
&#xD;
          -  Anatomical defects that preclude use of the device;&#xD;
&#xD;
          -  Treatment with botulinum toxin injections, urinary incontinence surgery or&#xD;
             implantation of artificial graft material, spinal or genitourinary surgery,&#xD;
             abdominoperineal resection of the rectum or radical hysterectomy (female)/&#xD;
             prostatectomy (male) within the last 6 months;&#xD;
&#xD;
          -  Previous treatment with sacral neuromodulation;&#xD;
&#xD;
          -  Diagnosis of pelvic pain disorders, stress incontinence, current urinary tract&#xD;
             infection, urinary stone and/or urinary tract malignancy; cystocele, enterocele or&#xD;
             rectocele of grade 3 or 4;&#xD;
&#xD;
          -  Previous or current pelvic radiotherapy and/or chemotherapy;&#xD;
&#xD;
          -  Severe uncontrolled diabetes;&#xD;
&#xD;
          -  Pregnant or lactating women or women planning a pregnancy&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Chiara Zecca, PD, MD</last_name>
    <role>Study Director</role>
    <affiliation>Ospedale Regionale di Lugano</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Ospedale Regionale di Lugano, Neurocenter of Southern Switzerland</name>
      <address>
        <city>Lugano</city>
        <state>Ticino</state>
        <zip>6903</zip>
        <country>Switzerland</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Switzerland</country>
  </location_countries>
  <verification_date>February 2021</verification_date>
  <study_first_submitted>November 15, 2018</study_first_submitted>
  <study_first_submitted_qc>November 22, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">November 27, 2018</study_first_posted>
  <last_update_submitted>February 2, 2021</last_update_submitted>
  <last_update_submitted_qc>February 2, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">February 4, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>Ente Ospedaliero Cantonale, Bellinzona</investigator_affiliation>
    <investigator_full_name>Chiara Zecca</investigator_full_name>
    <investigator_title>Principal Investigator</investigator_title>
  </responsible_party>
  <keyword>Multiple Sclerosis</keyword>
  <keyword>Lower Urinary Tract Symptoms</keyword>
  <keyword>Posterior tibial nerve stimulation</keyword>
  <keyword>Neuromodulation</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Multiple Sclerosis</mesh_term>
    <mesh_term>Sclerosis</mesh_term>
    <mesh_term>Lower Urinary Tract Symptoms</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/NCT03753698
org study id: EOC.NEUUR.1801
nct id: NCT03753698
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Prevalence of lower urinary tract symptoms (LUTS) in patients with MS increases with disease
      duration. Current management of urinary clinical symptoms in MS is mainly conservative. Its
      long-term outcome is often poor because of the progressive disease course and the treatment
      related side effects. Alternative therapeutic options are botulinum toxin injections,
      electrical stimulation of dorsal penile/clitoral nerve, and sacral nerve modulation.
      Posterior tibial nerve stimulation (PTNS) is a second minimally-invasive method of electrical
      stimulation. Multiple benefits may derive from the development and validation of a dedicated
      protocol of a new self-activated neuromodulation therapy, which may improve therapy
      compliance/effectiveness, quality of life and social life in MS patients with refractory
      LUTS. Furthermore, it may contribute to reduce outpatient visits, health costs and work
      absenteeism.

      To investigate the performance and safety of the medical device eCoin™ for the treatment of
      refractory LUTS in patients with MS over a period of 6 months.
This is a prospective, interventional, single arm, self-controlled pilot study in patients
      with multiple sclerosis and OAB symptoms with a 6-month treatment period of posterior tibial
      nerve stimulation with the medical device eCoin.

      It is a pilot study to explore the effectiveness and safety of using this device to treat MS
      patients with OAB in daily clinical practice in. Based on feasibility considerations, we plan
      to include approximately 20 patients.

      It consists of:

        1. wash-out period from PTNS treatment of at least 2 months;

        2. baseline assessments;

        3. implantation of eCoin;

        4. system activation; and

        5. treatment and follow-up visits for a 6-month period post implant activation. Seven
           Visits are foreseen during the trial.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Change from baseline in bladder volume (mL)
time frame: Baseline and Week 24
description: The patients will have their bladder filling volume measured during a urodynamic exam.
measure: Change from baseline of detrusor pressure amplitude (cmH2O)
time frame: Baseline and Week 24
description: The patients will have their detrusor pressure measured during an urodynamic exam.
measure: Change from baseline of cystometric capacity (mL)
time frame: Baseline and Week 24
description: The patients will have their cystometric capacity measured during an urodynamic exam.
measure: Change from baseline of bladder compliance (mL/cmH2O)
time frame: Baseline and Week 24
description: The patients will have their bladder compliance assessed during an urodynamic exam.
measure: Change from baseline of maximum detrusor pressure (cmH20) during storage phase
time frame: Baseline and Week 24
description: The patients will have their maximum detrusor pressure during storage phase measured during an urodynamic exam.
measure: Change from baseline of maximum detrusor pressure (cmH20) during voiding phase
time frame: Baseline and Week 24
description: The patients will have their maximum detrusor pressure during voiding phase measured during an urodynamic exam.
measure: Change from baseline of voided urine volume (mL)
time frame: Baseline and Week 24
description: The patients will have their voided urine volume measured during an urodynamic exam.
measure: Change from baseline of maximum urine flow rate (mL/s)
time frame: Baseline and Week 24
description: The patients will have the maximum urine flow rate measured during an urodynamic exam.
measure: Change from baseline of post void residual urine (mL)
time frame: Baseline and Week 24
description: The patients will have the post void residual urine measured during an urodynamic exam.
measure: Change from baseline of pelvic floor electromyographic activity
time frame: Baseline and Week 24
description: The patients will have presence or absence of pelvic floor activity recorded during an urodynamic exam.
measure: Change from baseline of vesico-uretero-renal reflux
time frame: Baseline and Week 24
description: The patients will have presence or absence of vesico-uretero-renal reflux assessed during an urodynamic exam.
measure: Change from baseline to 4, 12, and 24 weeks of bladder voiding assessed by means of a 3-day voiding diary
time frame: Baseline and Week 4, 12, 24
description: The patients will self-record their bladder voiding during three consecutive days at each time point including the number of voids/day, volume voided/void, number of leaks per day, degree of urgency prior to void (none, mild, moderate, severe, incontinence), number of self-catheterization needed through the day.
measure: Change from baseline to 4, 12, and 24 weeks of overactive bladder symptoms scores using the short form of the overactive bladder questionnaire OAB-q
time frame: Baseline, Week 4, 12, 24
description: The patients will rate their overactive bladder symptoms using the OAB-qSF questionnaire. It is self-administered and asks about how much a patients is bothered by selected bladder symptoms. It contains 6 questions about symptom severity and 13 on coping, sleeping, social life each to be rated on a 6-point scale (none of the time, a little of the time, some of the time, a good bit of the time, most of the time, all of the time). Symptom severity ranges from 6 (not bothered) to 36 (extremely bothered), impact on health related quality of life ranges from 13 (not bothered) to 78 (extremely bothered).
measure: Change from baseline to 4, 12, and 24 weeks of MSQOL54 scores.
time frame: Week -8, 4, 12, 24
description: The patients will assess their health related quality of life using the short form of the MSQOL 54 questionnaire. This is a self-administered multidimensional questionnaire on health-related quality of life with generic and multiple sclerosis specific questions on physical and mental health. The summary scores are derived from 12 subscales (physical function, physical role limitations, emotional role limitations, pain, emotional well-being, energy, health perceptions, social function, cognitive function, health distress, overall quality of life, sexual function). A low score indicates bad quality of life, a higher score improved quality of life (range 0-100).
measure: Treatment satisfaction, as measured on a composite visual analogue scale (VAS) score ranging from 0-100
time frame: Week 24
description: The patients will mark a point on a 100 mm long line with a pencil to indicate their treatment satisfaction. 0 (not satisfied at all), 100 (very satisfied).
measure: Incidence of adverse events
time frame: Week 0, 5, 12, 24
description: Number and proportion of patients experiencing device related adverse events during the study period will be recorded.
arm group label: eCoin
arm group type: Experimental
description: Neuromodulation of posterior tibial nerve
intervention type: Device
intervention name: eCoin
description: Implantation of device electrodes subcutaneous in lower tibia area;
Stimulation of posterior tibial nerves:
Regimen 1 (months 0-3): Six stimulation treatments per week, one stimulation per day, for duration of 30 minutes each Regimen 2 (months 3-6): Three stimulation treatments per week, one stimulation per day, for duration of 30 minutes each. Stimulation is activated by the patient.
arm group label: eCoin
criteria: 
gender: All
minimum age: 18 Years
maximum age: 80 Years
healthy volunteers: No
last name: Chiara Zecca, PD, MD
role: Study Director
affiliation: Ospedale Regionale di Lugano
facility: 
country: Switzerland
responsible party type: Sponsor-Investigator
investigator affiliation: Ente Ospedaliero Cantonale, Bellinzona
investigator full name: Chiara Zecca
investigator title: Principal Investigator
mesh term: Multiple Sclerosis
mesh term: Sclerosis
mesh term: Lower Urinary Tract Symptoms
sharing ipd: No