<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/NCT03835442</url>
  </required_header>
  <id_info>
    <org_study_id>S51996</org_study_id>
    <nct_id>NCT03835442</nct_id>
  </id_info>
  <brief_title>A Placebo Controlled Trial With Baclofen for the Treatment of GERD Patients With Incomplete PPI Response</brief_title>
  <official_title>A Placebo Controlled Trial With Baclofen for the Treatment of GERD Patients With Incomplete PPI Response</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Universitaire Ziekenhuizen KU Leuven</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Universitaire Ziekenhuizen KU Leuven</source>
  <oversight_info>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      Reflux (acid and non-acid) mainly occurs during transient LES relaxations (TLESRs). The&#xD;
      gamma-aminobutyric acid (GABA) receptor type B agonist baclofen was shown to inhibit TLESRs,&#xD;
      thereby significantly decreasing acid reflux after a meal in healthy controls and in patients&#xD;
      with GERD.&#xD;
&#xD;
      The primary objective of this study is to assess the efficacy (assessed by reflux symptom&#xD;
      questionnaire and pH-impedance recordings) of baclofen 10mg three times daily vs. placebo in&#xD;
      GERD patients with an incomplete response to PPI therapy.&#xD;
&#xD;
      The secondary objective is to assess the predictive value of reflux assessment (by&#xD;
      pH-impedance recordings) on the primary outcome.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a randomized, parallel, double-blind, placebo-controlled, out-patient, single-center&#xD;
      study. Eligible subjects will be randomly assigned to receive either oral baclofen 10 mg or&#xD;
      placebo t.i.d for a period 4 weeks. After 4 weeks all patients will be given the standard&#xD;
      dose of baclofen 10 mg t.i.d. (open label), for another 4 weeks. The b.i.d. PPI therapy will&#xD;
      be continued for the entire study duration.&#xD;
&#xD;
      Approximately 90 evaluable subjects with typical GERD symptoms (heartburn and/or&#xD;
      regurgitation) will participate in this study and will be randomized on a 1:1 basis: 45&#xD;
      subjects each will be in the placebo and baclofen 10 mg three times daily group. Subjects&#xD;
      will be considered to have completed the study if they complete the week 4 visit.&#xD;
&#xD;
      Medication will consist of identically-looking capsules of baclofen or placebo. Patients will&#xD;
      take 1 capsule containing 5 mg baclofen with meals t.i.d for 7 days and then 1 capsule&#xD;
      containing 10 mg baclofen with meals t.i.d for the remaining 21 days.&#xD;
&#xD;
      Prior to visit 1, all subjects included in the study will undergo a 24 hr pH-impedance study&#xD;
      which was requested by the treating physician. This investigation is part of the standard&#xD;
      clinical work up and will not be part of the study protocol.&#xD;
&#xD;
      Informed consent is to be signed and dated by the subject before any study related procedures&#xD;
      are performed. The date of each visit to the clinic and the date and time of the last dose of&#xD;
      test article will be recorded.&#xD;
&#xD;
      Throughout the study patients will be asked to complete daily a short questionnaire (ReQuest)&#xD;
      for reflux symptoms.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">January 2010</start_date>
  <completion_date type="Actual">January 2019</completion_date>
  <primary_completion_date type="Actual">December 2016</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <intervention_model_description>randomized, parallel, double-blind, placebo-controlled, out-patient, single-center study</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Triple (Participant, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>efficacy of baclofen on reflux symptom questionnaire</measure>
    <time_frame>Change from baseline in ReQuest scores at 4 weeks</time_frame>
    <description>To assess the effect of baclofen on reflux symptom questionnaire by ReQuest</description>
  </primary_outcome>
  <primary_outcome>
    <measure>efficacy of baclofen on pH-impedance recordings</measure>
    <time_frame>Change from baseline in reflux parameters (total number of reflux episodes) on 24h pH-impedance monitoring at 4 weeks</time_frame>
    <description>To assess of baclofen on 24 hour pH-impedance recordings</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Predictive value of the reflux monitoring</measure>
    <time_frame>Is SAP at baseline predictor of response at 4 weeks</time_frame>
    <description>To assess the predictive value of the 24 hour pH-impedance monitoring (symptom association probability = SAP) on the primary outcome</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">60</enrollment>
  <condition>Gastro Esophageal Reflux</condition>
  <arm_group>
    <arm_group_label>baclofen arm</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>baclofen 10mg tid for 4 weeks</description>
  </arm_group>
  <arm_group>
    <arm_group_label>placebos arm</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>placebo tid for 4 weeks</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Baclofen</intervention_name>
    <description>baclofen 10mg tid for 4 weeks</description>
    <arm_group_label>baclofen arm</arm_group_label>
    <other_name>Lioresal</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Placebos</intervention_name>
    <description>placebo tid for 4 weeks</description>
    <arm_group_label>placebos arm</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  18 - 75 years old&#xD;
&#xD;
          -  History of typical (heartburn/regurgitation) or atypical GERD symptoms during PPI&#xD;
             treatment, at least 3 times per week for 12 weeks. Daily intake of PPI treatment 12&#xD;
             weeks prior to inclusion.&#xD;
&#xD;
          -  Sexually active women of child bearing potential participating in the study must use a&#xD;
             medically acceptable form of contraception. Medically acceptable forms of&#xD;
             contraception include oral contraceptives, injectable or implantable methods,&#xD;
             intrauterine devices, or properly used barrier contraception.&#xD;
&#xD;
          -  Subjects must be capable of understanding and be willing to provide signed and dated&#xD;
             written voluntary informed consent before any protocol-specific screening procedures&#xD;
             are performed.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Endoscopic signs of severe erosive esophagitis (≥ grade C, Los Angeles classification)&#xD;
             on endoscopy performed during PPI treatment in the 6 months prior to screening.&#xD;
&#xD;
          -  Systemic diseases, known to affect esophageal motility.&#xD;
&#xD;
          -  Surgery in thorax or in the upper part of the abdomen.&#xD;
&#xD;
          -  Treatment with baclofen prior to the start of the study.&#xD;
&#xD;
          -  Regular use of medications such as: anticholinergics, tricycle antidepressants.&#xD;
&#xD;
          -  Significant neurological, respiratory, hepatic, renal, haematological, cardiovascular,&#xD;
             metabolic or gastroinestinal cerebrovascular disease as judged by the investigator&#xD;
&#xD;
          -  Absence of PPI intake for at least 2 consecutive days in the 2 weeks prior to the&#xD;
             screening.&#xD;
&#xD;
          -  Pregnancy or breast feeding.&#xD;
&#xD;
          -  History of poor compliance. History of/or current psychiatric illness that would&#xD;
             interfere with ability to comply with protocol requirements or give informed consent.&#xD;
             (well-compensated depression is allowed).&#xD;
&#xD;
          -  History of alcohol or drug abuse that would interfere with ability to comply with&#xD;
             protocol requirements.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Jan Tack, PhD, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>UZ Leuven</affiliation>
  </overall_official>
  <verification_date>February 2019</verification_date>
  <study_first_submitted>February 4, 2019</study_first_submitted>
  <study_first_submitted_qc>February 7, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">February 8, 2019</study_first_posted>
  <last_update_submitted>February 7, 2019</last_update_submitted>
  <last_update_submitted_qc>February 7, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">February 8, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Universitaire Ziekenhuizen KU Leuven</investigator_affiliation>
    <investigator_full_name>Prof Dr Jan Tack</investigator_full_name>
    <investigator_title>professor</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Gastroesophageal Reflux</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Baclofen</mesh_term>
  </intervention_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/NCT03835442
org study id: S51996
nct id: NCT03835442
lead sponsor: 
is fda regulated drug: No
is fda regulated device: No
is us export: No
Reflux (acid and non-acid) mainly occurs during transient LES relaxations (TLESRs). The
      gamma-aminobutyric acid (GABA) receptor type B agonist baclofen was shown to inhibit TLESRs,
      thereby significantly decreasing acid reflux after a meal in healthy controls and in patients
      with GERD.

      The primary objective of this study is to assess the efficacy (assessed by reflux symptom
      questionnaire and pH-impedance recordings) of baclofen 10mg three times daily vs. placebo in
      GERD patients with an incomplete response to PPI therapy.

      The secondary objective is to assess the predictive value of reflux assessment (by
      pH-impedance recordings) on the primary outcome.
This is a randomized, parallel, double-blind, placebo-controlled, out-patient, single-center
      study. Eligible subjects will be randomly assigned to receive either oral baclofen 10 mg or
      placebo t.i.d for a period 4 weeks. After 4 weeks all patients will be given the standard
      dose of baclofen 10 mg t.i.d. (open label), for another 4 weeks. The b.i.d. PPI therapy will
      be continued for the entire study duration.

      Approximately 90 evaluable subjects with typical GERD symptoms (heartburn and/or
      regurgitation) will participate in this study and will be randomized on a 1:1 basis: 45
      subjects each will be in the placebo and baclofen 10 mg three times daily group. Subjects
      will be considered to have completed the study if they complete the week 4 visit.

      Medication will consist of identically-looking capsules of baclofen or placebo. Patients will
      take 1 capsule containing 5 mg baclofen with meals t.i.d for 7 days and then 1 capsule
      containing 10 mg baclofen with meals t.i.d for the remaining 21 days.

      Prior to visit 1, all subjects included in the study will undergo a 24 hr pH-impedance study
      which was requested by the treating physician. This investigation is part of the standard
      clinical work up and will not be part of the study protocol.

      Informed consent is to be signed and dated by the subject before any study related procedures
      are performed. The date of each visit to the clinic and the date and time of the last dose of
      test article will be recorded.

      Throughout the study patients will be asked to complete daily a short questionnaire (ReQuest)
      for reflux symptoms.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: randomized, parallel, double-blind, placebo-controlled, out-patient, single-center study
primary purpose: Treatment
masking: Triple (Participant, Investigator, Outcomes Assessor)
measure: efficacy of baclofen on reflux symptom questionnaire
time frame: Change from baseline in ReQuest scores at 4 weeks
description: To assess the effect of baclofen on reflux symptom questionnaire by ReQuest
measure: efficacy of baclofen on pH-impedance recordings
time frame: Change from baseline in reflux parameters (total number of reflux episodes) on 24h pH-impedance monitoring at 4 weeks
description: To assess of baclofen on 24 hour pH-impedance recordings
measure: Predictive value of the reflux monitoring
time frame: Is SAP at baseline predictor of response at 4 weeks
description: To assess the predictive value of the 24 hour pH-impedance monitoring (symptom association probability = SAP) on the primary outcome
arm group label: baclofen arm
arm group type: Active Comparator
description: baclofen 10mg tid for 4 weeks
arm group label: placebos arm
arm group type: Placebo Comparator
description: placebo tid for 4 weeks
intervention type: Drug
intervention name: Baclofen
description: baclofen 10mg tid for 4 weeks
arm group label: baclofen arm
other name: Lioresal
intervention type: Other
intervention name: Placebos
description: placebo tid for 4 weeks
arm group label: placebos arm
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: No
last name: Jan Tack, PhD, MD
role: Principal Investigator
affiliation: UZ Leuven
responsible party type: Principal Investigator
investigator affiliation: Universitaire Ziekenhuizen KU Leuven
investigator full name: Prof Dr Jan Tack
investigator title: professor
mesh term: Gastroesophageal Reflux
mesh term: Baclofen
sharing ipd: No