<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/NCT01726751</url>
  </required_header>
  <id_info>
    <org_study_id>SCS-IBS-004</org_study_id>
    <nct_id>NCT01726751</nct_id>
  </id_info>
  <brief_title>Spinal Cord Stimulation for Pain Relief in Irritable Bowel Syndrome</brief_title>
  <official_title>Spinal Cord Stimulation in the Irritable Bowel Syndrome - a Randomized Cross-over Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Uppsala University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Medtronics, Inc.</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
    <collaborator>
      <agency>Bengt Ihre Foundation</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>The Swedish Society of Medicine</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Uppsala University</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      To elucidate Spinal Cord Stimulation (SCS) as treatment for IBS. An SCS system with a 4-polar&#xD;
      electrode at the T5-8 level is implanted. In a randomized, cross-over study design, active&#xD;
      stimulation is compared to a period without stimulation, with an ensuing tailing stimulation&#xD;
      period, twice as long. Patients recorded average pain level, pain attacks, number of&#xD;
      diarrheas and global quality of life. At the end of the study patients can choose to retain&#xD;
      their SCS stimulation system or have it removed.&#xD;
&#xD;
      The outcome of the present trial will show whether SCS is a useful treatment of IBS. The&#xD;
      long-term follow-up will show the continuous amelioration of SCS over at least six months.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The primary aim of the study is to investigate if the typical chronic abdominal pain in IBS&#xD;
      can be ameliorated by SCS. Secondary aims are possible effects of SCS on diarrhea or&#xD;
      constipation, quality of life and side effects, and further to evaluate the feasibility and&#xD;
      tolerability of SCS as validated by the willingness of the patients to retain the SCS&#xD;
      stimulation equipment.&#xD;
&#xD;
      Eligible patients are selected by a gastroenterologist for the study inclusion criteria: age&#xD;
      18-60, fulfilment of Rome II criteria, abdominal pain episodically reaching &gt; 4 on a 0-10&#xD;
      VAS, and stable symptoms for the past 2 years. A thorough clinical work-up is done to exclude&#xD;
      organic disease, including routine blood and electrolyte status, hepatic enzyme function and&#xD;
      lactose tolerance test as well as colonoscopy or colon x-ray. Patients with significant&#xD;
      somatic or psychiatric co-morbidity will be excluded.&#xD;
&#xD;
      Study design: A quadripolar SCS-lead (Quad-plus®, Medtronic Inc., Minnesota, USA) was&#xD;
      implanted via a percutaneous puncture at the Th11/12 level of the dorsal epidural space in&#xD;
      local anesthesia with the patient in the prone position. The electrode is advanced to the&#xD;
      mid-thoracic level, aiming for a final position around T6-T8, until intraoperative&#xD;
      stimulation yields paresthesias covering the abdomen . The electrode is then connected to an&#xD;
      impulse generator (Itrel-3®, Medtronic Inc.) implanted subcutaneously in the upper left&#xD;
      quadrant of the abdomen. Stimulation frequency will be set to 50 Hz for all patients but&#xD;
      other parameters (electrode pole combinations, amplitudes and pulse width) are adjusted and&#xD;
      set to produce adequate paresthesias of comfortable intensity.&#xD;
&#xD;
      During the subsequent ongoing trial reprogramming was allowed, if necessary for optimal&#xD;
      stimulation.&#xD;
&#xD;
      SCS will be started 2 weeks after surgery. Thereafter patients are randomized to either of&#xD;
      two study arms: one starting with SCS for a period of six weeks (A), and another with six&#xD;
      weeks without SCS (delayed start) (B). When on active SCS, patients are prompted to stimulate&#xD;
      8-12 h per day. Patients are instructed to increase the stimulation upon pain attack&#xD;
      break-through.&#xD;
&#xD;
      After six weeks, patients without stimulation were crossed-over to stimulation and vice&#xD;
      versa. After another six weeks both study arms included continued stimulation for additional&#xD;
      12 weeks up to 26 weeks. After a final 2-week period without stimulation the trial is&#xD;
      terminated.&#xD;
&#xD;
      During the whole study period patients will record, on a daily basis: 1) number of pain&#xD;
      attacks, 2) number of diarrhea episodes, 3) average pain level for the day (0-10) and 4)&#xD;
      average quality of life (0-10).&#xD;
&#xD;
      Patients are scheduled for regular controls, at 2, 8, 14, 26 and 28 weeks after implantation.&#xD;
      Patient compliance will be ensured, as the impulse generator stores information on the&#xD;
      percentage of elapsed time that stimulation has been in use.&#xD;
&#xD;
      At termination of the study participants were offered to keep the implanted SCS system or&#xD;
      have it removed.&#xD;
&#xD;
      All patients will be contacted for a structured telephone interview follow-up at a time-point&#xD;
      varying between 18 to 78 months after the study termination. A questionnaire was used to&#xD;
      assess present pain level, medication, use of the SCS system, side effects and global&#xD;
      satisfaction. Patients will also be asked whether they would have participated if they had&#xD;
      known the outcome in advance, and if they would recommend a trial of SCS treatment to someone&#xD;
      else with similar gastrointestinal problems.&#xD;
&#xD;
      All patients will be evaluated with the hospital anxiety and depression scale (HADS) and a&#xD;
      modified version of the gastrointestinal symptom rating scale for IBS (GSRS-IBS).&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>August 2005</start_date>
  <completion_date type="Actual">April 2014</completion_date>
  <primary_completion_date type="Actual">April 2014</primary_completion_date>
  <phase>Phase 1/Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Crossover Assignment</intervention_model>
    <intervention_model_description>Spinal cord stimulation</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Single (Participant)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>To investigate if typical abdominal pain of IBS can be ameliorated by SCS?</measure>
    <time_frame>According to protocol for 26 weeks</time_frame>
    <description>During the whole study period each patient will record the number of pain attacks.&#xD;
Patients are scheduled for regular outpatient controls, at 2, 8, 14, 26 and 28 weeks after implantation</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>To record effects of SCS on diarrhea/constipation</measure>
    <time_frame>According to protocol for 26 weeks</time_frame>
    <description>During the whole study period each patient recorded, on a daily basis: 1) number of pain attacks, 2) number of diarrhea episodes, 3) average pain level for the day and 4) assessment of average quality of life. For the latter two items patients were instructed to use a numerical rating scale (NRS) with a range of 0-10.&#xD;
Patients were scheduled for regular outpatient controls, at 2, 8, 14, 26 and 28 weeks after implantation</description>
  </secondary_outcome>
  <other_outcome>
    <measure>To evaluate quality of life and side effects, feasibility and tolerability of SCS, validated as willingness to retain the stimulation equipment.</measure>
    <time_frame>According to protocol for 26 weeks</time_frame>
    <description>During the whole study period each patient recorded, on a daily basis: 1) number of pain attacks, 2) number of diarrhea episodes, 3) average pain level for the day and 4) assessment of average quality of life. For the latter two items patients were instructed to use a numerical rating scale (NRS) with a range of 0-10.&#xD;
Patients were scheduled for regular outpatient controls, at 2, 8, 14, 26 and 28 weeks after implantation.</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">10</enrollment>
  <condition>Irritable Bowel Syndrome</condition>
  <condition>Constipation</condition>
  <condition>Diarrhea</condition>
  <condition>Pain</condition>
  <arm_group>
    <arm_group_label>Early off-stimulation (group B)</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>Late SCS treatment. After 2 weeks without SCS, randomization to either of two study arms: Group B starting with no SCS for a period of six weeks (A) followed by a period of active SCS (on-period for 6 weeks). Thereafter, free stimulation for 12 weeks, followed by a concluding 2 sweeks of no SCS.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Early on-stimulation (group A)</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>Early SCS treatment. After 2 weeks without SCS, randomization to either of two study arms: Group A starting with SCS for a period of six weeks (A) followed by a period of no SCS (off-period for 6 weeks). Thereafter, free stimulation for 12 weeks, followed by a concluding 2 sweeks of no SCS.</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Spinal Cord Stimultion (SCS)</intervention_name>
    <description>Electric stimulation of the spinal cord</description>
    <arm_group_label>Early off-stimulation (group B)</arm_group_label>
    <arm_group_label>Early on-stimulation (group A)</arm_group_label>
    <other_name>Quad-plus®, Medtronic Inc., MN, USA</other_name>
  </intervention>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Spinal cord nerve stimulation</intervention_name>
    <arm_group_label>Early off-stimulation (group B)</arm_group_label>
    <arm_group_label>Early on-stimulation (group A)</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  age 18-60, Rome II criteria, abdominal pain &gt;4 (0-10 VAS), stable symptoms for &gt;2&#xD;
             years&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  other gastrointestinal disease, somatic or psychiatric co-morbidity&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>60 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Per M Hellström, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Uppsala University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Karolinska University Hospital</name>
      <address>
        <city>Solna</city>
        <state>Stockholm</state>
        <zip>17176</zip>
        <country>Sweden</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Sweden</country>
  </location_countries>
  <verification_date>November 2018</verification_date>
  <study_first_submitted>October 30, 2012</study_first_submitted>
  <study_first_submitted_qc>November 9, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 15, 2012</study_first_posted>
  <last_update_submitted>November 5, 2018</last_update_submitted>
  <last_update_submitted_qc>November 5, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">November 7, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Uppsala University</investigator_affiliation>
    <investigator_full_name>Per Hellström</investigator_full_name>
    <investigator_title>Professor, senior consultant</investigator_title>
  </responsible_party>
  <keyword>Spinal cord stimulation</keyword>
  <keyword>Irritable bowel syndrome</keyword>
  <keyword>Abdominal pain</keyword>
  <keyword>Diarrhea</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Irritable Bowel Syndrome</mesh_term>
    <mesh_term>Syndrome</mesh_term>
    <mesh_term>Constipation</mesh_term>
    <mesh_term>Diarrhea</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/NCT01726751
org study id: SCS-IBS-004
nct id: NCT01726751
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
has dmc: No
To elucidate Spinal Cord Stimulation (SCS) as treatment for IBS. An SCS system with a 4-polar
      electrode at the T5-8 level is implanted. In a randomized, cross-over study design, active
      stimulation is compared to a period without stimulation, with an ensuing tailing stimulation
      period, twice as long. Patients recorded average pain level, pain attacks, number of
      diarrheas and global quality of life. At the end of the study patients can choose to retain
      their SCS stimulation system or have it removed.

      The outcome of the present trial will show whether SCS is a useful treatment of IBS. The
      long-term follow-up will show the continuous amelioration of SCS over at least six months.
The primary aim of the study is to investigate if the typical chronic abdominal pain in IBS
      can be ameliorated by SCS. Secondary aims are possible effects of SCS on diarrhea or
      constipation, quality of life and side effects, and further to evaluate the feasibility and
      tolerability of SCS as validated by the willingness of the patients to retain the SCS
      stimulation equipment.

      Eligible patients are selected by a gastroenterologist for the study inclusion criteria: age
      18-60, fulfilment of Rome II criteria, abdominal pain episodically reaching > 4 on a 0-10
      VAS, and stable symptoms for the past 2 years. A thorough clinical work-up is done to exclude
      organic disease, including routine blood and electrolyte status, hepatic enzyme function and
      lactose tolerance test as well as colonoscopy or colon x-ray. Patients with significant
      somatic or psychiatric co-morbidity will be excluded.

      Study design: A quadripolar SCS-lead (Quad-plus®, Medtronic Inc., Minnesota, USA) was
      implanted via a percutaneous puncture at the Th11/12 level of the dorsal epidural space in
      local anesthesia with the patient in the prone position. The electrode is advanced to the
      mid-thoracic level, aiming for a final position around T6-T8, until intraoperative
      stimulation yields paresthesias covering the abdomen . The electrode is then connected to an
      impulse generator (Itrel-3®, Medtronic Inc.) implanted subcutaneously in the upper left
      quadrant of the abdomen. Stimulation frequency will be set to 50 Hz for all patients but
      other parameters (electrode pole combinations, amplitudes and pulse width) are adjusted and
      set to produce adequate paresthesias of comfortable intensity.

      During the subsequent ongoing trial reprogramming was allowed, if necessary for optimal
      stimulation.

      SCS will be started 2 weeks after surgery. Thereafter patients are randomized to either of
      two study arms: one starting with SCS for a period of six weeks (A), and another with six
      weeks without SCS (delayed start) (B). When on active SCS, patients are prompted to stimulate
      8-12 h per day. Patients are instructed to increase the stimulation upon pain attack
      break-through.

      After six weeks, patients without stimulation were crossed-over to stimulation and vice
      versa. After another six weeks both study arms included continued stimulation for additional
      12 weeks up to 26 weeks. After a final 2-week period without stimulation the trial is
      terminated.

      During the whole study period patients will record, on a daily basis: 1) number of pain
      attacks, 2) number of diarrhea episodes, 3) average pain level for the day (0-10) and 4)
      average quality of life (0-10).

      Patients are scheduled for regular controls, at 2, 8, 14, 26 and 28 weeks after implantation.
      Patient compliance will be ensured, as the impulse generator stores information on the
      percentage of elapsed time that stimulation has been in use.

      At termination of the study participants were offered to keep the implanted SCS system or
      have it removed.

      All patients will be contacted for a structured telephone interview follow-up at a time-point
      varying between 18 to 78 months after the study termination. A questionnaire was used to
      assess present pain level, medication, use of the SCS system, side effects and global
      satisfaction. Patients will also be asked whether they would have participated if they had
      known the outcome in advance, and if they would recommend a trial of SCS treatment to someone
      else with similar gastrointestinal problems.

      All patients will be evaluated with the hospital anxiety and depression scale (HADS) and a
      modified version of the gastrointestinal symptom rating scale for IBS (GSRS-IBS).
allocation: Randomized
intervention model: Crossover Assignment
intervention model description: Spinal cord stimulation
primary purpose: Treatment
masking: Single (Participant)
measure: To investigate if typical abdominal pain of IBS can be ameliorated by SCS?
time frame: According to protocol for 26 weeks
description: During the whole study period each patient will record the number of pain attacks.
Patients are scheduled for regular outpatient controls, at 2, 8, 14, 26 and 28 weeks after implantation
measure: To record effects of SCS on diarrhea/constipation
time frame: According to protocol for 26 weeks
description: During the whole study period each patient recorded, on a daily basis: 1) number of pain attacks, 2) number of diarrhea episodes, 3) average pain level for the day and 4) assessment of average quality of life. For the latter two items patients were instructed to use a numerical rating scale (NRS) with a range of 0-10.
Patients were scheduled for regular outpatient controls, at 2, 8, 14, 26 and 28 weeks after implantation
measure: To evaluate quality of life and side effects, feasibility and tolerability of SCS, validated as willingness to retain the stimulation equipment.
time frame: According to protocol for 26 weeks
description: During the whole study period each patient recorded, on a daily basis: 1) number of pain attacks, 2) number of diarrhea episodes, 3) average pain level for the day and 4) assessment of average quality of life. For the latter two items patients were instructed to use a numerical rating scale (NRS) with a range of 0-10.
Patients were scheduled for regular outpatient controls, at 2, 8, 14, 26 and 28 weeks after implantation.
arm group label: Early off-stimulation (group B)
arm group type: Other
description: Late SCS treatment. After 2 weeks without SCS, randomization to either of two study arms: Group B starting with no SCS for a period of six weeks (A) followed by a period of active SCS (on-period for 6 weeks). Thereafter, free stimulation for 12 weeks, followed by a concluding 2 sweeks of no SCS.
arm group label: Early on-stimulation (group A)
arm group type: Other
description: Early SCS treatment. After 2 weeks without SCS, randomization to either of two study arms: Group A starting with SCS for a period of six weeks (A) followed by a period of no SCS (off-period for 6 weeks). Thereafter, free stimulation for 12 weeks, followed by a concluding 2 sweeks of no SCS.
intervention type: Device
intervention name: Spinal Cord Stimultion (SCS)
description: Electric stimulation of the spinal cord
arm group label: Early off-stimulation (group B)
arm group label: Early on-stimulation (group A)
other name: Quad-plus®, Medtronic Inc., MN, USA
intervention type: Device
intervention name: Spinal cord nerve stimulation
arm group label: Early off-stimulation (group B)
arm group label: Early on-stimulation (group A)
criteria: 
gender: All
minimum age: 18 Years
maximum age: 60 Years
healthy volunteers: No
last name: Per M Hellström, MD, PhD
role: Principal Investigator
affiliation: Uppsala University
facility: 
country: Sweden
responsible party type: Principal Investigator
investigator affiliation: Uppsala University
investigator full name: Per Hellström
investigator title: Professor, senior consultant
mesh term: Irritable Bowel Syndrome
mesh term: Syndrome
mesh term: Constipation
mesh term: Diarrhea