<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/NCT02210975</url>
  </required_header>
  <id_info>
    <org_study_id>NL4834906814</org_study_id>
    <nct_id>NCT02210975</nct_id>
  </id_info>
  <brief_title>An Investigation of Electrical Stimulation on Gastroesophageal Reflux Disease (GERD) in Patients After Sleeve Gastrectomy</brief_title>
  <official_title>An Investigation of Electrical Stimulation on Gastroesophageal Reflux Disease (GERD) in Patients After Sleeve Gastrectomy</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Maastricht University Medical Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>EndoStim Inc.</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Maastricht University Medical Center</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Sleeve gastrectomy (SG) has gained popularity as both a staged and a definitive procedure for&#xD;
      morbid obesity due to its technical simplicity, low-morbidity and excellent results both for&#xD;
      weight loss and control of metabolic syndrome. There are however reports of SG worsening&#xD;
      pre-existing GERD or causing new-onset GERD. Because of this, patients with pre-existing GERD&#xD;
      have been denied the benefits of SG. In addition, patients that develop post-op GERD cannot&#xD;
      undergo traditional anti-reflux surgery since the gastric fundus that is required for&#xD;
      fundoplication is removed during the SG. Hence, patients with post-SG GERD not adequately&#xD;
      controlled with medication can only opt for the more invasive gastric bypass procedure as&#xD;
      their only surgical treatment option.&#xD;
&#xD;
      In a recently reported case study, an obese patient with severe GERD successfully treated&#xD;
      with EndoStim underwent SG and maintained adequate GERD control with continued use of LES&#xD;
      stimulation therapy. However electrical stimulation was not yet tested systematically in&#xD;
      patients with prior gastric operation such as sleeve gastrectomy.&#xD;
&#xD;
      This study will test the hypothesis that electrical stimulation is effective in control of&#xD;
      GERD associated with SG.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date>July 2014</start_date>
  <completion_date type="Anticipated">February 2016</completion_date>
  <primary_completion_date type="Anticipated">January 2016</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>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>The incidence and severity of any complications that are associated with the investigational stimulation device throughout the follow-up period.</measure>
    <time_frame>up to 12 month follow-up</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Efficacy - Disease specific quality of life</measure>
    <time_frame>Baseline, 6 and 12 month follow up</time_frame>
    <description>The change in patient's GERD-HRQL, where applicable, from baseline (as measured while off PPI) .</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>pH-monitoring</measure>
    <time_frame>Baseline, 6 and 12 month FU</time_frame>
    <description>The change in baseline pH values of % 24-hour esophageal pH&lt; 4.0 and number of reflux events &gt;1minute and &gt;5 minute duration with the same on-stimulation pH parameters at 6 months and at 12 months.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Questionnairres, symptom diary</measure>
    <time_frame>baseline, 6 and 12 month FU</time_frame>
    <description>Change in symptoms frequency and severity at 6 months vs. baseline and at 12 months vs. baseline as measured by patient symptom diary, structured GI questionnaire, and patients quality of life measured by SF-12.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Anti-secretory medication use</measure>
    <time_frame>Baseline, 6 and 12 month FU</time_frame>
    <description>Change in anti-secretory medication use as evaluated during the two weeks prior to the 6 mo and 12 mo follow up compared to baseline.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>HR-manometry</measure>
    <time_frame>Baseline, 6 and 12 month FU</time_frame>
    <description>Change in LES end expiratory pressure (LESPpre) and the on-stimulation LES end expiratory pressure (LESPpost) at 6 months and 12 months in mmHg.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">10</enrollment>
  <condition>GERD</condition>
  <condition>Sleeve Gastrectomy</condition>
  <arm_group>
    <arm_group_label>Electrical Stimulation Therapy</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>LES-Stimulation Device</intervention_name>
    <arm_group_label>Electrical Stimulation Therapy</arm_group_label>
    <other_name>EndoStim b.v.</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Subject is between 18 - 80 years of age.&#xD;
&#xD;
          2. Subject underwent a sleeve gastrectomy minimum one year prior to enrollment (in order&#xD;
             to have reached a stable weight loss plateau).&#xD;
&#xD;
          3. Subject has a history of heartburn, regurgitation or both for &gt;6 month prompting&#xD;
             physician recommendation of continual daily use of PPI after sleeve gastrectomy.&#xD;
&#xD;
          4. Baseline off-PPI GERD-HRQL score ≥ 20 following 10-14 days off PPI&#xD;
&#xD;
          5. Baseline off-PPI GERD-HRQLscore is at least 5 points higher than the on-PPI score or a&#xD;
             positive relationship between the occurrence of their primary symptom during the pH&#xD;
             impedance monitoring (symptom association probability ≥ 95% or a SI score ≥ 50%) is&#xD;
             present.&#xD;
&#xD;
          6. Subject who are on standard medical therapy for 6 months or longer and experience&#xD;
             discomfort or who are otherwise dissatisfied with GERD symptoms.&#xD;
&#xD;
          7. Subjects with a GERD condition that in the opinion of the PI justifies a minimally&#xD;
             invasive reversible procedure prior to attempting a more drastic procedure such as a&#xD;
             gastric bypass.&#xD;
&#xD;
          8. Subject has exhibited excessive lower esophageal acid exposure during 24-hour pH-metry&#xD;
             of antisecretory therapy performed within 6 months of screening visit; pH &lt; 4 for &gt; 6%&#xD;
             of total time.&#xD;
&#xD;
          9. Subject has a resting LES end expiratory pressure ≥ 5mmHg on manometry performed&#xD;
             within 6 months of enrollment.&#xD;
&#xD;
         10. Subject has no esophagitis or esophagitis ≤ Grade C (LA classification) on upper&#xD;
             endoscopy within 6 months of enrollment.&#xD;
&#xD;
         11. Subject has esophageal body contraction amplitude &gt; 30 mmHg for &gt;30% of swallows and &gt;&#xD;
             30% peristaltic contractions on manometry.&#xD;
&#xD;
         12. Subject has signed the informed consent form and is able to adhere to study visit&#xD;
             schedule.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Subject has any non-GERD esophageal motility disorders.&#xD;
&#xD;
          2. Subject has evidence of obstruction or stricture in the gastric sleeve by a barium&#xD;
             swallow and endoscopy.&#xD;
&#xD;
          3. Subject has any significant multisystem diseases.&#xD;
&#xD;
          4. Subject has an autoimmune or a connective tissue disorder (e.g. scleroderma,&#xD;
             dematomyositis, Calcinosis-Raynaud's-Esophagus Sclerodactyly Syndrome (CREST),&#xD;
             Sjogren's Syndrome, Sharp's Syndrome) requiring therapy in the preceding 2 years.&#xD;
&#xD;
          5. Subject has Barrett's epithelium (&gt; M2; &gt;C1) or any grade of dysplasia.&#xD;
&#xD;
          6. Subject has a hiatal hernia larger than 3 cm.&#xD;
&#xD;
          7. Subject has a body mass index (BMI) greater than 35 kg/m2.&#xD;
&#xD;
          8. Subject has Type 1 Diabetes Mellitus&#xD;
&#xD;
          9. Subject has uncontrolled Type 2 Diabetes Mellitus (T2DM) defined as HbA1c &gt;9.5 in the&#xD;
             previous 6 months, or has T2DM for &gt; 10 years.&#xD;
&#xD;
         10. Subject has a history of suspected or confirmed esophageal or gastric cancer.&#xD;
&#xD;
         11. Subject has esophageal or gastric varices.&#xD;
&#xD;
         12. Subject has significant cardiac arrhythmia or ectopy or significant cardiovascular&#xD;
             disease.&#xD;
&#xD;
         13. Subject has an existing implanted electrical stimulator (e.g., pacemaker, AICD).&#xD;
&#xD;
         14. Subject requires chronic anticoagulant therapy.&#xD;
&#xD;
         15. Subject has dysphagia or esophageal peptic stricture, excluding Schatzki's ring.&#xD;
&#xD;
         16. Subject of child-bearing potential who is pregnant or intends to become pregnant&#xD;
             during the trial period.&#xD;
&#xD;
         17. Subject is currently enrolled in other potentially confounding research.&#xD;
&#xD;
         18. History of any malignancy in the last 2 years.&#xD;
&#xD;
         19. Subject has any condition that, at the discretion of the investigator, would preclude&#xD;
             participation in the trial.&#xD;
&#xD;
         20. Weight change of +/- 10% of the EWL (Excess Weight Loss) in the 3 months prior to&#xD;
             enrollment.&#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_contact>
    <last_name>Nicolaas F Rinsma, MD</last_name>
    <phone>+31433884190</phone>
    <email>n.rinsma@maastrichtuniversity.nl</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Selwyn van Rijn, MD</last_name>
    <phone>+3143375021</phone>
    <email>selwyn.van.rijn@mumc.nl</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Maastricht University Medical Center</name>
      <address>
        <city>Maastricht</city>
        <zip>6229 HX</zip>
        <country>Netherlands</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Nicolaas F Rinsma, MD</last_name>
      <phone>+31433884190</phone>
      <email>n.rinsma@maastrichtuniversity.nl</email>
    </contact>
    <investigator>
      <last_name>Nicole D. Bouvy, MD PhD</last_name>
      <role>Principal Investigator</role>
    </investigator>
    <investigator>
      <last_name>José M Conchillo, MD PhD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Nicolaas F. Rinsma, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Selwyn Van Rijn, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>Netherlands</country>
  </location_countries>
  <verification_date>August 2014</verification_date>
  <study_first_submitted>August 4, 2014</study_first_submitted>
  <study_first_submitted_qc>August 6, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 7, 2014</study_first_posted>
  <last_update_submitted>August 6, 2014</last_update_submitted>
  <last_update_submitted_qc>August 6, 2014</last_update_submitted_qc>
  <last_update_posted type="Estimate">August 7, 2014</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>GERD</keyword>
  <keyword>LES</keyword>
  <keyword>Sleeve Gastrectomy</keyword>
  <keyword>Electrical Stimulation Therapy</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Gastroesophageal Reflux</mesh_term>
  </condition_browse>
  <pending_results>
    <submitted>November 28, 2018</submitted>
    <returned>March 15, 2019</returned>
    <submitted>September 2, 2020</submitted>
    <returned>September 23, 2020</returned>
  </pending_results>
  <!-- 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/NCT02210975
org study id: NL4834906814
nct id: NCT02210975
lead sponsor: 
collaborator: 
has dmc: Yes
Sleeve gastrectomy (SG) has gained popularity as both a staged and a definitive procedure for
      morbid obesity due to its technical simplicity, low-morbidity and excellent results both for
      weight loss and control of metabolic syndrome. There are however reports of SG worsening
      pre-existing GERD or causing new-onset GERD. Because of this, patients with pre-existing GERD
      have been denied the benefits of SG. In addition, patients that develop post-op GERD cannot
      undergo traditional anti-reflux surgery since the gastric fundus that is required for
      fundoplication is removed during the SG. Hence, patients with post-SG GERD not adequately
      controlled with medication can only opt for the more invasive gastric bypass procedure as
      their only surgical treatment option.

      In a recently reported case study, an obese patient with severe GERD successfully treated
      with EndoStim underwent SG and maintained adequate GERD control with continued use of LES
      stimulation therapy. However electrical stimulation was not yet tested systematically in
      patients with prior gastric operation such as sleeve gastrectomy.

      This study will test the hypothesis that electrical stimulation is effective in control of
      GERD associated with SG.
allocation: Non-Randomized
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: The incidence and severity of any complications that are associated with the investigational stimulation device throughout the follow-up period.
time frame: up to 12 month follow-up
measure: Efficacy - Disease specific quality of life
time frame: Baseline, 6 and 12 month follow up
description: The change in patient's GERD-HRQL, where applicable, from baseline (as measured while off PPI) .
measure: pH-monitoring
time frame: Baseline, 6 and 12 month FU
description: The change in baseline pH values of % 24-hour esophageal pH< 4.0 and number of reflux events >1minute and >5 minute duration with the same on-stimulation pH parameters at 6 months and at 12 months.
measure: Questionnairres, symptom diary
time frame: baseline, 6 and 12 month FU
description: Change in symptoms frequency and severity at 6 months vs. baseline and at 12 months vs. baseline as measured by patient symptom diary, structured GI questionnaire, and patients quality of life measured by SF-12.
measure: Anti-secretory medication use
time frame: Baseline, 6 and 12 month FU
description: Change in anti-secretory medication use as evaluated during the two weeks prior to the 6 mo and 12 mo follow up compared to baseline.
measure: HR-manometry
time frame: Baseline, 6 and 12 month FU
description: Change in LES end expiratory pressure (LESPpre) and the on-stimulation LES end expiratory pressure (LESPpost) at 6 months and 12 months in mmHg.
arm group label: Electrical Stimulation Therapy
arm group type: Experimental
intervention type: Device
intervention name: LES-Stimulation Device
arm group label: Electrical Stimulation Therapy
other name: EndoStim b.v.
criteria: 
gender: All
minimum age: 18 Years
maximum age: 80 Years
healthy volunteers: No
last name: Nicolaas F Rinsma, MD
phone: +31433884190
email: n.rinsma@maastrichtuniversity.nl
last name: Selwyn van Rijn, MD
phone: +3143375021
email: selwyn.van.rijn@mumc.nl
facility: 
status: Recruiting
contact: 
investigator: 
investigator: 
investigator: 
investigator: 
country: Netherlands
responsible party type: Sponsor
mesh term: Gastroesophageal Reflux
submitted: November 28, 2018
returned: March 15, 2019
submitted: September 2, 2020
returned: September 23, 2020