<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/NCT01718457</url>
  </required_header>
  <id_info>
    <org_study_id>SHEBA-12-9626-GL-CTIL</org_study_id>
    <nct_id>NCT01718457</nct_id>
  </id_info>
  <brief_title>Endobarrier Treatment in Obese Subjects With T2DM</brief_title>
  <official_title>Endobarrier Treatment in Obese Subjects With T2DM</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Sheba Medical Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Sheba Medical Center</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Diabesity (Diabetes accompanied by obesity) is a prevalent condition many times complicated&#xD;
      by micro- and macrovascular disease. Many treatments for Diabesity paradoxically cause&#xD;
      further weight gain and hypoglycemia. The Endobarrier enables diabetes control along with&#xD;
      weight loss as an alternative to bariatric surgery for patients who are not interested or not&#xD;
      qualified for surgery. The aim of this study is to assess the efficacy and safety of the&#xD;
      Endobarrier Diabesity patients in Israel.&#xD;
&#xD;
      This study will include 45 men and women between the ages of 18-65 with HbA1c level of 8% and&#xD;
      above and a BMI of 30 kg/m2 or above.&#xD;
&#xD;
      Exclusion criteria: use of anti-coagulant, use of steroids or inability to discontinue these&#xD;
      medications.&#xD;
&#xD;
      The cohort will be followed for two years during which the patients will be monitored for&#xD;
      diabetes control (by using a continuous glucose monitor), weight, blood pressure, lipid&#xD;
      profile, fatty liver (by Ultrasound and blood markers for inflammation and fibrosis) and&#xD;
      change in plasma gut peptide levels. The Endobarrier will be explanted after one year,&#xD;
      however the monitoring of the patients will continue for another year.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Current therapies including diet, exercise, behavior modifications, oral diabetes agents, and&#xD;
      insulin, are employed to control Type 2 Diabetes mellitus (T2DM), but rarely return subjects&#xD;
      to euglycemia, require dose escalation over time and can be associated with hypoglycemia and&#xD;
      weight gain. Obesity is a well-established risk for both the development of diabetes as well&#xD;
      as for increased mortality. The majority of individuals with T2DM are overweight or obese.&#xD;
      Obesity and type 2 diabetes mellitus are common and well documented risk factors for&#xD;
      non-alcoholic fatty liver disease (NAFLD). For some patients NAFLD disease is a relatively&#xD;
      benign condition, for others NAFLD will progress to cirrhosis and end-stage liver disease&#xD;
      with associated complications including hepatocellular carcino.The current treatment for&#xD;
      NAFLD and nonalcoholic steatohepatitis (NASH) is weight reduction which can be achieved by&#xD;
      life style modifications, drug therapy or bariatric surgery. The Fibro Test and Fibro Max&#xD;
      have proven their efficacy as noninvasive biomarkers for NAFLD and NASH in large scale&#xD;
      studies. Transient Elastography which measures liver stiffness non-invasively has been&#xD;
      successful in identifying fibrosis in NAFLD.&#xD;
&#xD;
      In addition, designated sonography is a sensitive noninvasive method for steatosis&#xD;
      quantification which can diagnose small amounts of liver fat that would be missed by&#xD;
      conventional sonography and is not affected by fibrosis or steatohepatitis.&#xD;
&#xD;
      Bariatric Surgery for T2DM In light of this, bariatric surgery has recently emerged as one of&#xD;
      the most effective means of providing durable, clinically-significant resolution of diabetes.&#xD;
      The majority of subjects with T2DM who undergo these procedures have remission of this&#xD;
      disorder. In a large bariatric surgery meta-analysis published in Journal of the American&#xD;
      Medical Association in 2004, within studies reporting resolution of diabetes, 76.8% of&#xD;
      subjects experienced complete resolution; within studies reporting both resolution and&#xD;
      improvement or only improvement of diabetes, 85.4% of subjects experienced resolution or&#xD;
      improvement of diabetes. All bariatric operations result in remarkable improvement in T2DM&#xD;
      although with varying degrees of efficacy. Resolution of diabetes often occurs within days&#xD;
      following bariatric surgery, even before marked weight loss is achieved. Resolution of&#xD;
      diabetes is more prevalent following the more &quot;malabsorptive&quot; procedures (BPD or duodenal&#xD;
      switch) and the mixed malabsorptive/restrictive Roux-en-y (RYGB) in contrast to the purely&#xD;
      restrictive vertical banded gastroplasty (VBG) and laparoscopic adjustable gastric banding&#xD;
      (LAGB) procedures. In addition, there appears to be a gradation of diabetes resolution as a&#xD;
      function of the operative procedure: 98.9% for BPD, 83.7% for RYGB, 71.6% for VBG, and 47.9%&#xD;
      for LAGB. Subjects with the shortest duration and mildest form of T2DM had a higher rate of&#xD;
      T2DM resolution after surgery, suggesting that early surgical intervention is warranted to&#xD;
      increase the likelihood of rendering subjects euglycemic. Recently, it has been published&#xD;
      that subjects with long-standing uncontrolled diabetes and non-morbid obesity have a high&#xD;
      remission rate (88%) of their diabetes following RYGB surgery. However, despite the&#xD;
      considerable effectiveness shown by bariatric surgery in resolving diabetes, surgery has not&#xD;
      yet become a standard of care for subjects who are obese with diabetes. In part because of an&#xD;
      incomplete understanding of the mechanisms of action, this concept of gastrointestinal&#xD;
      surgery as an endocrine modifier is not yet fully embraced by the clinical community and has&#xD;
      yet to be incorporated into care strategies.12 But perhaps more importantly, some clinicians&#xD;
      evoke the irreversibility of gastric bypass and the occasional reports of poor outcomes to&#xD;
      label this approach &quot;extreme&quot; - to be reserved as a treatment of last resort.&#xD;
&#xD;
      Bariatric Surgery for NAFLD Weight loss following bariatric surgery results in a marked&#xD;
      improvement in hepatic steatosis. An analysis of numerous paired biopsy studies reveals&#xD;
      convincing evidence that significant improvement in steatosis and inflammation occurs in&#xD;
      NAFLD patients after weight loss surgery. Regression and histologic improvement of NASH has&#xD;
      been documented after bariatric surgery.&#xD;
&#xD;
      The &quot;EndoBarrier&quot; Gastrointestinal Liner System is an endoscopically-delivered device that&#xD;
      offers an alternative to gastric bypass surgery. The device shields the duodenum and upper&#xD;
      jejunum from contact with chyme, thereby mimicking the foregut bypass effect of a RYGB&#xD;
      procedure without altering the subject's anatomy. Pancreatic and biliary secretions pass&#xD;
      along the outside of the device and then mix with chyme in the upper jejunum. Based on animal&#xD;
      experiments and clinical observations, the EndoBarrier device may provide a useful&#xD;
      non-surgical intervention for treating T2DM, with an added benefit of weight loss. To date,&#xD;
      over 13 studies enrolling over 500 subjects were performed with the EndoBarrier device. In&#xD;
      one study, at 12 months 23/32 uncontrolled T2DM subjects (71.9%), were able to achieve an&#xD;
      HbA1c value less than or equal to 7.0%.&#xD;
&#xD;
      The product offers a minimally invasive reversible alternative to a fully surgical approach.&#xD;
      Since it is delivered and retrieved endoscopically, the device has the option of being&#xD;
      removed if necessary and without changing a subject's anatomy.&#xD;
&#xD;
      Encouraging early clinical trial results, support continued investigating of the device for a&#xD;
      T2DM indication. To date, there are over 400,000 diabetic subjects in Israel and in 90% of&#xD;
      the cases the diabetes can be related to overweight. Over 50% of these patients are not well&#xD;
      controlled.&#xD;
&#xD;
      Device Description - ENDOBARRIER The EndoBarrier Gastrointestinal Liner system received&#xD;
      European Community mark (CE) on 11 December 2009 and is indicated for the treatment of&#xD;
      obesity and Type 2 diabetes. The implant is indicated for a maximum implant duration period&#xD;
      of twelve months. The intent of the EndoBarrier is to facilitate glycemic control and weight&#xD;
      loss by mimicking portions of the Roux-en-Y bypass procedure. The device consists of 3&#xD;
      components: the implant, the delivery system, and the removal system.&#xD;
&#xD;
      The procedure entails bypassing the duodenum and the proximal jejunum with a 60 cm&#xD;
      non-permeable polymeric sleeve which is attached to the duodenal wall. This sleeve prevents&#xD;
      the contact of food with the duodenal wall, thereby re-capitulating one of the major&#xD;
      properties of the Roux-en-Y (RYGB) operation.&#xD;
&#xD;
      With this technique, control of diabetes is accompanied by weight loss, with no need for&#xD;
      medications that may cause weight gain / hypoglycemia and may serve to replace or postpone&#xD;
      surgery. In a recent paper by de Moura et al, Twenty-two subjects with uncontrolled type 2&#xD;
      diabetes and a body mass index between 40- 60 kg/m ² were implanted with the EndoBarrier and&#xD;
      followed prospectively for 1 year.&#xD;
&#xD;
      The authors found statistically significant reductions in fasting blood glucose (- 30.3 ±&#xD;
      10.2 mg/dL), fasting insulin (- 7.3 ± 2.6 units/mL), and HbA1c ( -2.1±0.3%) in patients&#xD;
      undergoing the procedure. The study conclusions were that EndoBarrier improves glycemic&#xD;
      status in obese subjects with diabetes and therefore represents a non-surgical, reversible&#xD;
      alternative to bariatric surgery. Internal data from GI Dynamics reveals that obese subject&#xD;
      (average BMI of 44 kg/m²) and uncontrolled diabetes (average A1c of 8.4 %) who were implanted&#xD;
      with EndoBarrier for one year showed: a reduction of 2.1% of the A1c level, with a value of&#xD;
      less than 7% in 80% of the subjects, an average reduction of 20 Kg (representing 16% of the&#xD;
      excess weight), a 29% reduction in the triglyceride level and a 14% reduction in LDL-c.&#xD;
&#xD;
      After 12 months the EndoBarrier was removed and the subjects remained in follow up for&#xD;
      additional 18 months. During this period, the achievement was maintained This is an&#xD;
      open-label two phase trail investigating the effect of an EndoBarrier sleeve on diabetes&#xD;
      control and body weight in diabetic obese subjects.&#xD;
&#xD;
      Objectives: The purpose of this study is to evaluate the efficacy of EndoBarrier in treatment&#xD;
      of diabetes and obesity&#xD;
&#xD;
      Secondary Objectives:&#xD;
&#xD;
        1. To examine the effect of the EndoBarrier as a model for the proximal effects of the RYGB&#xD;
           surgery in terms of diabetes control.&#xD;
&#xD;
        2. To explore the weight independent mechanisms by which the Endobarrier improves diabetes.&#xD;
&#xD;
        3. To test the effect of Endobarrier implantation on liver steatosis, steatohepatitis and&#xD;
           fibrosis.&#xD;
&#xD;
      Methods and assessments:&#xD;
&#xD;
      Visit 1- screening: All potential patients will be screened for eligibility at visit 1.&#xD;
&#xD;
      The following activities will occur on Visit 1: The patient signs the informed consent form&#xD;
      (for the main trail and the sensor procedure). Inclusion / Exclusion criteria will be&#xD;
      reviewed.&#xD;
&#xD;
      Demographic: Date of birth, gender. Medical history evaluation and concomitant medication&#xD;
      record. Diabetes history treatment record: onset date of diabetes, type, total dose and start&#xD;
      date of current treatment. A physical examination and Electrocardiogram (ECG) will be&#xD;
      conducted. Fasting Laboratory measurements will be performed visit 2 - gastro screening&#xD;
&#xD;
      Patient will arrive at the site fasted. The following activities will occur on Visit 2:&#xD;
&#xD;
      Gastroscopy will be performed. 40 mg of Omeprazole twice daily 3 days prior to visit 4 will&#xD;
      be initiated.&#xD;
&#xD;
      Visit 3 - sensor insertion &amp; Liver tests Patient will arrive at the site fasted. Patients&#xD;
      will arrive at the site 2 days before the planned device implantation. The patient should be&#xD;
      fasting in visit 3.&#xD;
&#xD;
      The following activities will occur on Visit 3: Fasting Laboratory measurements will be&#xD;
      performed. Ultrasound for elastography and hepatic fat content will be performed.&#xD;
&#xD;
      Sensor insertion will be performed. The patient will be asked to answer the &quot;Visual analog&#xD;
      scale&quot; (VAS) questionnaire. Dietary consultation will be performed Visit 4 - Endobarrier&#xD;
      implantation: The patient will arrive in a fasting state.&#xD;
&#xD;
      Under full anesthesia, gastroscopy will be performed and a guide wire will be inserted to the&#xD;
      jejunum. The Endobarrirer device will be inserted over the guide wire and introduced into the&#xD;
      duodenal bulb. Under fluoroscopy the device will be operated and the sleeve will be released&#xD;
      from its capsule. Contrast material will be injected thorough the sleeve to insure full&#xD;
      opening. After full expansion of the sleeve, the anchoring mechanism will be operated and the&#xD;
      sleeve will be anchored by small hooks to the duodenal bulb. Correct hooking will be&#xD;
      visualized endoscopically.&#xD;
&#xD;
      visits 5-17: Vital signs, weight, waist circumferences will be measured. Fasting Laboratory&#xD;
      measurements will be performed. Diabetes and diet consultation will be performed.&#xD;
&#xD;
      visit 18: Endobarrier retrieval: Vital signs, weight, waist circumferences will be measured.&#xD;
      Fasting Laboratory measurements will be performed. Patient will be asked to answer the VAS&#xD;
      questionnaire. Diabetes and diet consultation will be performed.&#xD;
&#xD;
      The retrieval procedure will be performed after sedation: A retrieval hood will be connected&#xD;
      to the endoscope tip, a scope will be introduced to the duodenum, a retrieval grasper will be&#xD;
      inserted through the scope, by pulling the drawstring the anchoring hook will collapse and&#xD;
      when all hooks are within the plastic retrieval hood the endoscope will be withdrawn safely&#xD;
      out.&#xD;
&#xD;
      visit 19-22: follow up : Vital signs, weight, waist circumferences will be measured. Fasting&#xD;
      Laboratory measurements will be performed Diabetes and diet consultation will be performed.&#xD;
&#xD;
      Withdrawal criteria:&#xD;
&#xD;
      The patient may be withdrawn from the study at the discretion of the investigator due to a&#xD;
      safety concern, such as: Intractable abdominal pain ,Intractable vomiting, Upper GI bleeding,&#xD;
      the need for initiation of Non-steroidal anti-inflammatory drugs (NSAIDs), Aspirin or any&#xD;
      other drugs with bleeding as a potential side effect (i.e. Coumadin).&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Active, not recruiting</last_known_status>
  <start_date>December 2012</start_date>
  <completion_date type="Anticipated">January 2018</completion_date>
  <primary_completion_date type="Anticipated">December 2016</primary_completion_date>
  <phase>Phase 4</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>percent change in HbA1c level</measure>
    <time_frame>1 year, 2 years</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>percent change in BMI</measure>
    <time_frame>1 year, 2 years</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>percent change in LDL cholesterol levels</measure>
    <time_frame>1 year, 2 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>change in waist circumference</measure>
    <time_frame>1 year, 2 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>change in fasting plasma glucose level</measure>
    <time_frame>1 year, 2 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>percent change in HDL cholesterol levels</measure>
    <time_frame>1 year, 2 year</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>percent in Triglycerides levels</measure>
    <time_frame>1 year, 2 years</time_frame>
  </secondary_outcome>
  <other_outcome>
    <measure>change in degree of fatty liver</measure>
    <time_frame>1 year, 2 years</time_frame>
    <description>liver enzymes, liver ultrasound, fibromax tests</description>
  </other_outcome>
  <other_outcome>
    <measure>change in plasma gut peptide levels</measure>
    <time_frame>1 year, 2 years</time_frame>
    <description>GLP-1, PYY, Oxynthomodulin, Ghrelin</description>
  </other_outcome>
  <other_outcome>
    <measure>change in plasma insulin level</measure>
    <time_frame>1 year, 2 years</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>change in C-peptide levels</measure>
    <time_frame>1 year, 2 years</time_frame>
  </other_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">45</enrollment>
  <condition>Type 2 Diabetes</condition>
  <condition>Obesity</condition>
  <arm_group>
    <arm_group_label>Endobarrier device insertion</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Endobarrier</intervention_name>
    <arm_group_label>Endobarrier device insertion</arm_group_label>
    <other_name>Duodenal-Jejunal Bypass Liner</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Subjects willing to comply with study requirements and have signed an informed consent&#xD;
             form.&#xD;
&#xD;
          2. Age 18-65&#xD;
&#xD;
          3. BMI ≥ 30 kg/m²&#xD;
&#xD;
          4. HbA1c% as assessed by central laboratory ≥ 8.0%.&#xD;
&#xD;
          5. Documented negative pregnancy test in women of childbearing potential.&#xD;
&#xD;
          6. Women of childbearing potential agree to remain on contraceptives for the duration of&#xD;
             their trial participation.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Subjects taking systemic corticosteroids or drugs known to affect GI motility within&#xD;
             30 days prior to randomization&#xD;
&#xD;
          2. Subjects receiving any prescription or over the counter weight loss medication within&#xD;
             30 days prior to randomization (including GLP-1 analogs).&#xD;
&#xD;
          3. Previous GI surgery that could preclude the ability to place the EndoBarrier device,&#xD;
             liner or affect the function of the implant&#xD;
&#xD;
          4. Subjects with a history of abnormal GI anatomical findings documented on imaging&#xD;
             study, which in the opinion of the Investigator, may impair implantation of the&#xD;
             EndoBarrier device&#xD;
&#xD;
          5. Subjects with active GERD not taking a Proton Pump Inhibitor (PPI)&#xD;
&#xD;
          6. Subjects with symptomatic kidney stones within 6 months prior to randomization.&#xD;
&#xD;
          7. Known abnormal pathologies or conditions of the gastrointestinal tract, including&#xD;
             ulcers or Crohn's disease, atresias or stenoses, upper gastro-intestinal bleeding&#xD;
             conditions&#xD;
&#xD;
          8. Subjects with symptomatic gallstones within 6 months prior to randomization&#xD;
&#xD;
          9. Coagulopathy defined as hgb &lt;10g/dl and platelet &lt; 100,000/ml or diagnosis of&#xD;
             hemophilia, factor X deficiencies or fibrinogen abnormalities&#xD;
&#xD;
         10. Any documented history of acute or chronic pancreatitis&#xD;
&#xD;
         11. Subjects requiring prescription antithrombotic therapy (i.e. anticoagulant or&#xD;
             antiplatelet agent)&#xD;
&#xD;
         12. Subjects unable to discontinue Aspirin or any other NSAIDs (non-steroidal&#xD;
             anti-inflammatory drugs) or any other drugs with bleeding as a potential side effect&#xD;
             (i.e coumadin) during the study duration&#xD;
&#xD;
         13. Known diagnosis of systemic lupus erythematosus, scleroderma or other autoimmune&#xD;
             connective tissue disorder&#xD;
&#xD;
         14. Subject is or has been enrolled in another investigational study within 3 months of&#xD;
             participation into the EndoBarrier study&#xD;
&#xD;
         15. Subjects with poor dentition who cannot completely chew their food.&#xD;
&#xD;
         16. Subjects with thyroid disease unless controlled with a therapeutic dose of medication&#xD;
             and have normal thyroid function tests for a minimum of 6 months prior to&#xD;
             randomization&#xD;
&#xD;
         17. Subjects not residing within a 3 hour driving distance of the study center.&#xD;
&#xD;
         18. Subjects with an abnormal laboratory or ECG abnormality which the investigators deems&#xD;
             clinically significant and makes the patient a poor candidate for the study&#xD;
&#xD;
         19. Subjects with known allergies or hypersensitivity to ceftrixone, cephalosporins or&#xD;
             penicillin&#xD;
&#xD;
             -&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Gabriella Segal-Lieberman, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Sheba Medical Center</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Sheba medical center, Tel-Hashomer</name>
      <address>
        <city>Ramat-Gan</city>
        <zip>52621</zip>
        <country>Israel</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Israel</country>
  </location_countries>
  <results_reference>
    <citation>de Moura EG, Martins BC, Lopes GS, Orso IR, de Oliveira SL, Galvao Neto MP, Santo MA, Sakai P, Ramos AC, Garrido Junior AB, Mancini MC, Halpern A, Cecconello I. Metabolic improvements in obese type 2 diabetes subjects implanted for 1 year with an endoscopically deployed duodenal-jejunal bypass liner. Diabetes Technol Ther. 2012 Feb;14(2):183-9. doi: 10.1089/dia.2011.0152. Epub 2011 Sep 20.</citation>
    <PMID>21932999</PMID>
  </results_reference>
  <verification_date>June 2014</verification_date>
  <study_first_submitted>October 29, 2012</study_first_submitted>
  <study_first_submitted_qc>October 29, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 31, 2012</study_first_posted>
  <last_update_submitted>June 30, 2014</last_update_submitted>
  <last_update_submitted_qc>June 30, 2014</last_update_submitted_qc>
  <last_update_posted type="Estimate">July 1, 2014</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Endobarrier</keyword>
  <keyword>Diabetes</keyword>
  <keyword>Obesity</keyword>
  <keyword>Weight</keyword>
  <keyword>BMI</keyword>
  <keyword>Lipid profile</keyword>
  <keyword>fatty liver</keyword>
  <keyword>gut peptides</keyword>
  <keyword>HbA1c</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Obesity</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/NCT01718457
org study id: SHEBA-12-9626-GL-CTIL
nct id: NCT01718457
lead sponsor: 
has dmc: No
Diabesity (Diabetes accompanied by obesity) is a prevalent condition many times complicated
      by micro- and macrovascular disease. Many treatments for Diabesity paradoxically cause
      further weight gain and hypoglycemia. The Endobarrier enables diabetes control along with
      weight loss as an alternative to bariatric surgery for patients who are not interested or not
      qualified for surgery. The aim of this study is to assess the efficacy and safety of the
      Endobarrier Diabesity patients in Israel.

      This study will include 45 men and women between the ages of 18-65 with HbA1c level of 8% and
      above and a BMI of 30 kg/m2 or above.

      Exclusion criteria: use of anti-coagulant, use of steroids or inability to discontinue these
      medications.

      The cohort will be followed for two years during which the patients will be monitored for
      diabetes control (by using a continuous glucose monitor), weight, blood pressure, lipid
      profile, fatty liver (by Ultrasound and blood markers for inflammation and fibrosis) and
      change in plasma gut peptide levels. The Endobarrier will be explanted after one year,
      however the monitoring of the patients will continue for another year.
Current therapies including diet, exercise, behavior modifications, oral diabetes agents, and
      insulin, are employed to control Type 2 Diabetes mellitus (T2DM), but rarely return subjects
      to euglycemia, require dose escalation over time and can be associated with hypoglycemia and
      weight gain. Obesity is a well-established risk for both the development of diabetes as well
      as for increased mortality. The majority of individuals with T2DM are overweight or obese.
      Obesity and type 2 diabetes mellitus are common and well documented risk factors for
      non-alcoholic fatty liver disease (NAFLD). For some patients NAFLD disease is a relatively
      benign condition, for others NAFLD will progress to cirrhosis and end-stage liver disease
      with associated complications including hepatocellular carcino.The current treatment for
      NAFLD and nonalcoholic steatohepatitis (NASH) is weight reduction which can be achieved by
      life style modifications, drug therapy or bariatric surgery. The Fibro Test and Fibro Max
      have proven their efficacy as noninvasive biomarkers for NAFLD and NASH in large scale
      studies. Transient Elastography which measures liver stiffness non-invasively has been
      successful in identifying fibrosis in NAFLD.

      In addition, designated sonography is a sensitive noninvasive method for steatosis
      quantification which can diagnose small amounts of liver fat that would be missed by
      conventional sonography and is not affected by fibrosis or steatohepatitis.

      Bariatric Surgery for T2DM In light of this, bariatric surgery has recently emerged as one of
      the most effective means of providing durable, clinically-significant resolution of diabetes.
      The majority of subjects with T2DM who undergo these procedures have remission of this
      disorder. In a large bariatric surgery meta-analysis published in Journal of the American
      Medical Association in 2004, within studies reporting resolution of diabetes, 76.8% of
      subjects experienced complete resolution; within studies reporting both resolution and
      improvement or only improvement of diabetes, 85.4% of subjects experienced resolution or
      improvement of diabetes. All bariatric operations result in remarkable improvement in T2DM
      although with varying degrees of efficacy. Resolution of diabetes often occurs within days
      following bariatric surgery, even before marked weight loss is achieved. Resolution of
      diabetes is more prevalent following the more "malabsorptive" procedures (BPD or duodenal
      switch) and the mixed malabsorptive/restrictive Roux-en-y (RYGB) in contrast to the purely
      restrictive vertical banded gastroplasty (VBG) and laparoscopic adjustable gastric banding
      (LAGB) procedures. In addition, there appears to be a gradation of diabetes resolution as a
      function of the operative procedure: 98.9% for BPD, 83.7% for RYGB, 71.6% for VBG, and 47.9%
      for LAGB. Subjects with the shortest duration and mildest form of T2DM had a higher rate of
      T2DM resolution after surgery, suggesting that early surgical intervention is warranted to
      increase the likelihood of rendering subjects euglycemic. Recently, it has been published
      that subjects with long-standing uncontrolled diabetes and non-morbid obesity have a high
      remission rate (88%) of their diabetes following RYGB surgery. However, despite the
      considerable effectiveness shown by bariatric surgery in resolving diabetes, surgery has not
      yet become a standard of care for subjects who are obese with diabetes. In part because of an
      incomplete understanding of the mechanisms of action, this concept of gastrointestinal
      surgery as an endocrine modifier is not yet fully embraced by the clinical community and has
      yet to be incorporated into care strategies.12 But perhaps more importantly, some clinicians
      evoke the irreversibility of gastric bypass and the occasional reports of poor outcomes to
      label this approach "extreme" - to be reserved as a treatment of last resort.

      Bariatric Surgery for NAFLD Weight loss following bariatric surgery results in a marked
      improvement in hepatic steatosis. An analysis of numerous paired biopsy studies reveals
      convincing evidence that significant improvement in steatosis and inflammation occurs in
      NAFLD patients after weight loss surgery. Regression and histologic improvement of NASH has
      been documented after bariatric surgery.

      The "EndoBarrier" Gastrointestinal Liner System is an endoscopically-delivered device that
      offers an alternative to gastric bypass surgery. The device shields the duodenum and upper
      jejunum from contact with chyme, thereby mimicking the foregut bypass effect of a RYGB
      procedure without altering the subject's anatomy. Pancreatic and biliary secretions pass
      along the outside of the device and then mix with chyme in the upper jejunum. Based on animal
      experiments and clinical observations, the EndoBarrier device may provide a useful
      non-surgical intervention for treating T2DM, with an added benefit of weight loss. To date,
      over 13 studies enrolling over 500 subjects were performed with the EndoBarrier device. In
      one study, at 12 months 23/32 uncontrolled T2DM subjects (71.9%), were able to achieve an
      HbA1c value less than or equal to 7.0%.

      The product offers a minimally invasive reversible alternative to a fully surgical approach.
      Since it is delivered and retrieved endoscopically, the device has the option of being
      removed if necessary and without changing a subject's anatomy.

      Encouraging early clinical trial results, support continued investigating of the device for a
      T2DM indication. To date, there are over 400,000 diabetic subjects in Israel and in 90% of
      the cases the diabetes can be related to overweight. Over 50% of these patients are not well
      controlled.

      Device Description - ENDOBARRIER The EndoBarrier Gastrointestinal Liner system received
      European Community mark (CE) on 11 December 2009 and is indicated for the treatment of
      obesity and Type 2 diabetes. The implant is indicated for a maximum implant duration period
      of twelve months. The intent of the EndoBarrier is to facilitate glycemic control and weight
      loss by mimicking portions of the Roux-en-Y bypass procedure. The device consists of 3
      components: the implant, the delivery system, and the removal system.

      The procedure entails bypassing the duodenum and the proximal jejunum with a 60 cm
      non-permeable polymeric sleeve which is attached to the duodenal wall. This sleeve prevents
      the contact of food with the duodenal wall, thereby re-capitulating one of the major
      properties of the Roux-en-Y (RYGB) operation.

      With this technique, control of diabetes is accompanied by weight loss, with no need for
      medications that may cause weight gain / hypoglycemia and may serve to replace or postpone
      surgery. In a recent paper by de Moura et al, Twenty-two subjects with uncontrolled type 2
      diabetes and a body mass index between 40- 60 kg/m ² were implanted with the EndoBarrier and
      followed prospectively for 1 year.

      The authors found statistically significant reductions in fasting blood glucose (- 30.3 ±
      10.2 mg/dL), fasting insulin (- 7.3 ± 2.6 units/mL), and HbA1c ( -2.1±0.3%) in patients
      undergoing the procedure. The study conclusions were that EndoBarrier improves glycemic
      status in obese subjects with diabetes and therefore represents a non-surgical, reversible
      alternative to bariatric surgery. Internal data from GI Dynamics reveals that obese subject
      (average BMI of 44 kg/m²) and uncontrolled diabetes (average A1c of 8.4 %) who were implanted
      with EndoBarrier for one year showed: a reduction of 2.1% of the A1c level, with a value of
      less than 7% in 80% of the subjects, an average reduction of 20 Kg (representing 16% of the
      excess weight), a 29% reduction in the triglyceride level and a 14% reduction in LDL-c.

      After 12 months the EndoBarrier was removed and the subjects remained in follow up for
      additional 18 months. During this period, the achievement was maintained This is an
      open-label two phase trail investigating the effect of an EndoBarrier sleeve on diabetes
      control and body weight in diabetic obese subjects.

      Objectives: The purpose of this study is to evaluate the efficacy of EndoBarrier in treatment
      of diabetes and obesity

      Secondary Objectives:

        1. To examine the effect of the EndoBarrier as a model for the proximal effects of the RYGB
           surgery in terms of diabetes control.

        2. To explore the weight independent mechanisms by which the Endobarrier improves diabetes.

        3. To test the effect of Endobarrier implantation on liver steatosis, steatohepatitis and
           fibrosis.

      Methods and assessments:

      Visit 1- screening: All potential patients will be screened for eligibility at visit 1.

      The following activities will occur on Visit 1: The patient signs the informed consent form
      (for the main trail and the sensor procedure). Inclusion / Exclusion criteria will be
      reviewed.

      Demographic: Date of birth, gender. Medical history evaluation and concomitant medication
      record. Diabetes history treatment record: onset date of diabetes, type, total dose and start
      date of current treatment. A physical examination and Electrocardiogram (ECG) will be
      conducted. Fasting Laboratory measurements will be performed visit 2 - gastro screening

      Patient will arrive at the site fasted. The following activities will occur on Visit 2:

      Gastroscopy will be performed. 40 mg of Omeprazole twice daily 3 days prior to visit 4 will
      be initiated.

      Visit 3 - sensor insertion & Liver tests Patient will arrive at the site fasted. Patients
      will arrive at the site 2 days before the planned device implantation. The patient should be
      fasting in visit 3.

      The following activities will occur on Visit 3: Fasting Laboratory measurements will be
      performed. Ultrasound for elastography and hepatic fat content will be performed.

      Sensor insertion will be performed. The patient will be asked to answer the "Visual analog
      scale" (VAS) questionnaire. Dietary consultation will be performed Visit 4 - Endobarrier
      implantation: The patient will arrive in a fasting state.

      Under full anesthesia, gastroscopy will be performed and a guide wire will be inserted to the
      jejunum. The Endobarrirer device will be inserted over the guide wire and introduced into the
      duodenal bulb. Under fluoroscopy the device will be operated and the sleeve will be released
      from its capsule. Contrast material will be injected thorough the sleeve to insure full
      opening. After full expansion of the sleeve, the anchoring mechanism will be operated and the
      sleeve will be anchored by small hooks to the duodenal bulb. Correct hooking will be
      visualized endoscopically.

      visits 5-17: Vital signs, weight, waist circumferences will be measured. Fasting Laboratory
      measurements will be performed. Diabetes and diet consultation will be performed.

      visit 18: Endobarrier retrieval: Vital signs, weight, waist circumferences will be measured.
      Fasting Laboratory measurements will be performed. Patient will be asked to answer the VAS
      questionnaire. Diabetes and diet consultation will be performed.

      The retrieval procedure will be performed after sedation: A retrieval hood will be connected
      to the endoscope tip, a scope will be introduced to the duodenum, a retrieval grasper will be
      inserted through the scope, by pulling the drawstring the anchoring hook will collapse and
      when all hooks are within the plastic retrieval hood the endoscope will be withdrawn safely
      out.

      visit 19-22: follow up : Vital signs, weight, waist circumferences will be measured. Fasting
      Laboratory measurements will be performed Diabetes and diet consultation will be performed.

      Withdrawal criteria:

      The patient may be withdrawn from the study at the discretion of the investigator due to a
      safety concern, such as: Intractable abdominal pain ,Intractable vomiting, Upper GI bleeding,
      the need for initiation of Non-steroidal anti-inflammatory drugs (NSAIDs), Aspirin or any
      other drugs with bleeding as a potential side effect (i.e. Coumadin).
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: percent change in HbA1c level
time frame: 1 year, 2 years
measure: percent change in BMI
time frame: 1 year, 2 years
measure: percent change in LDL cholesterol levels
time frame: 1 year, 2 years
measure: change in waist circumference
time frame: 1 year, 2 years
measure: change in fasting plasma glucose level
time frame: 1 year, 2 years
measure: percent change in HDL cholesterol levels
time frame: 1 year, 2 year
measure: percent in Triglycerides levels
time frame: 1 year, 2 years
measure: change in degree of fatty liver
time frame: 1 year, 2 years
description: liver enzymes, liver ultrasound, fibromax tests
measure: change in plasma gut peptide levels
time frame: 1 year, 2 years
description: GLP-1, PYY, Oxynthomodulin, Ghrelin
measure: change in plasma insulin level
time frame: 1 year, 2 years
measure: change in C-peptide levels
time frame: 1 year, 2 years
arm group label: Endobarrier device insertion
arm group type: Experimental
intervention type: Device
intervention name: Endobarrier
arm group label: Endobarrier device insertion
other name: Duodenal-Jejunal Bypass Liner
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: No
last name: Gabriella Segal-Lieberman, MD
role: Principal Investigator
affiliation: Sheba Medical Center
facility: 
country: Israel
citation: de Moura EG, Martins BC, Lopes GS, Orso IR, de Oliveira SL, Galvao Neto MP, Santo MA, Sakai P, Ramos AC, Garrido Junior AB, Mancini MC, Halpern A, Cecconello I. Metabolic improvements in obese type 2 diabetes subjects implanted for 1 year with an endoscopically deployed duodenal-jejunal bypass liner. Diabetes Technol Ther. 2012 Feb;14(2):183-9. doi: 10.1089/dia.2011.0152. Epub 2011 Sep 20.
PMID: 21932999
responsible party type: Sponsor
mesh term: Obesity