<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/NCT04428619</url>
  </required_header>
  <id_info>
    <org_study_id>IRB# 19-001796</org_study_id>
    <nct_id>NCT04428619</nct_id>
  </id_info>
  <brief_title>Percutaneous Electrical Nerve Field Stimulation for Adults With Irritable Bowel Syndrome</brief_title>
  <official_title>Neuromodulation With Percutaneous Electrical Nerve Field Stimulation for Adults With Irritable Bowel Syndrome: A Randomized, Double-Blind, Sham-Controlled Pilot Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of California, Los Angeles</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Innovative Health Solutions</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>University of California, Los Angeles</source>
  <oversight_info>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>Yes</is_fda_regulated_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a prospective, double-blind, randomized, sham-controlled pilot study evaluating the&#xD;
      efficacy of percutaneous electrical nerve field stimulation for the treatment of adult&#xD;
      patients with irritable bowel syndrome (IBS).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      IBS has a worldwide prevalence around 11% and is characterized by chronic or recurrent&#xD;
      abdominal pain associated with altered bowel habits. Abnormalities within the brain-gut axis,&#xD;
      visceral hypersensitivity, and dysfunction of the autonomic nervous system are important&#xD;
      components contributing to the pathophysiology of IBS. Despite recent advances in medical&#xD;
      therapies for IBS, a significant subgroup of patients fails to experience satisfactory relief&#xD;
      of abdominal pain. Given evidence of anti-inflammatory and anti-nociceptive components of&#xD;
      vagal nerve pathways, peripheral field stimulation of the vagus nerve may help reduce&#xD;
      abdominal pain in patients with IBS.&#xD;
&#xD;
      Percutaneous electrical nerve field stimulation (PENFS) administered via the IB-Stim device&#xD;
      (Innovative Health Solutions, Versailles, IN, USA) has been shown to be efficacious in&#xD;
      adolescent patients with abdominal-pain-related functional GI disorders, including IBS. This&#xD;
      device uses discontinuous frequencies of stimulation to target central pain pathways through&#xD;
      branches of cranial nerves V, VII, IX, and X that innervate the external ear and project to&#xD;
      certain brainstem nuclei, including the nucleus tractus solitarius (NTS). The NTS then acts&#xD;
      as a relay station to other brain areas involved in pain modulation and autonomic control,&#xD;
      including the rostral ventral medulla, locus coeruleus, hypothalamus, and amygdala. In&#xD;
      adolescent studies, PENFS was associated with a greater reduction in worst abdominal pain and&#xD;
      composite abdominal pain scores from baseline as well as compared with a sham device after&#xD;
      three weeks of treatment. These effects were sustained over an extended follow-up period with&#xD;
      minimal to no side effects. In addition, a greater proportion of adolescents in the PENFS arm&#xD;
      achieved at least a 30% reduction in worst abdominal pain scores from baseline after 3 weeks&#xD;
      of treatment.&#xD;
&#xD;
      The IB-Stim is the first device to be approved by the Food and Drug Administration (FDA) for&#xD;
      the treatment of functional abdominal pain in adolescents aged 11-18 with IBS. However, the&#xD;
      efficacy of PENFS in adults with IBS is not currently known. This study is a double-blind,&#xD;
      randomized, sham-controlled pilot study evaluating the efficacy of PENFS using IB-Stim for&#xD;
      the treatment of IBS symptoms in adult patients with IBS.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">August 1, 2020</start_date>
  <completion_date type="Anticipated">November 30, 2024</completion_date>
  <primary_completion_date type="Anticipated">May 1, 2024</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>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Single (Investigator)</masking>
    <masking_description>Patients who meet study eligibility criteria will be randomly assigned (1:1) in blocks of two and four, using a code generated by a randomization program to 4 weeks of stimulation with an active or inactive (sham) PENFS device. Per manufacturer design, both active stimulation and sham are below a detectable sensation threshold. Allocation will be concealed, and all physicians, statisticians, participants, and research coordinators will be unaware of device codes. One research coordinator who has no patient contact will be unblinded and handle allocation and storage of devices. At the end of 4 weeks, patients will be asked to which device arm they believe they were randomized.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Mean change in IBS symptom severity from baseline</measure>
    <time_frame>Week 4</time_frame>
    <description>To compare the efficacy of PENFS therapy versus sham therapy on the change in IBS symptom severity in adult IBS patients after 4 weeks of treatment, assessed through a mean change in the IBS-SSS.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Mean change in IBS symptom severity from baseline</measure>
    <time_frame>Week 8</time_frame>
    <description>To compare the efficacy of PENFS therapy versus sham therapy on the change in IBS symptom severity in adult IBS patients at extended follow-up (8 weeks), assessed through a mean change in the IBS-SSS.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>IBS symptom severity responder rate</measure>
    <time_frame>Week 4</time_frame>
    <description>To compare the efficacy of PENFS therapy versus sham therapy on the change in IBS symptom severity in adult IBS patients after 4 weeks of treatment compared to baseline. Participants will be considered responders if there is at least a 50-point reduction on the IBS-SSS.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Daily worst abdominal pain responder rate</measure>
    <time_frame>Week 4</time_frame>
    <description>To compare the proportion of adult patients with IBS who experience a change of ≥ 30% from baseline in average daily worst abdominal pain scores after 4 weeks of treatment (measured using a validated, 11-point numeric rating scale). Participants who have a reduction in daily worst abdominal pain scores of ≥ 30% from baseline will be considered clinical responders.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mean change in average daily worst abdominal pain from baseline</measure>
    <time_frame>Week 4</time_frame>
    <description>To compare the efficacy of PENFS therapy versus sham therapy on mean worst daily abdominal pain scores after 4 weeks compared to baseline in adult patients with IBS</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in average weekly abdominal pain symptoms from baseline</measure>
    <time_frame>Week 4, week 8</time_frame>
    <description>To compare the efficacy of PENFS therapy versus sham therapy on the change in average weekly abdominal pain symptoms after 4 weeks of treatment and at extended follow-up (8 weeks) compared to baseline, assessed through the PROMIS Gastrointestinal Belly Pain Scale (percentiles 2-100%; higher percentiles indicate worse abdominal pain).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in average daily stool consistency from baseline</measure>
    <time_frame>Week 4</time_frame>
    <description>To compare the efficacy of PENFS therapy versus sham therapy on the change in average daily stool consistency after 4 weeks of treatment compared to baseline, assessed using the Bristol Stool Form Scale (BSFS) (stool types 1-7; types 1 and 2 indicate constipation, types 3 and 4 are normal consistency stools, type 5 indicates stool lacking fiber, types 6 and 7 indicate diarrhea).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in average weekly bowel habits from baseline</measure>
    <time_frame>Week 4, week 8</time_frame>
    <description>To compare the efficacy of PENFS therapy versus sham therapy on the change in average weekly bowel habits after 4 weeks of treatment and at extended follow-up (8 weeks) compared to baseline, assessed through the PROMIS Gastrointestinal Constipation Scale (percentiles 0.3-100%; higher percentiles indicate greater constipation) and Gastrointestinal Diarrhea Scale (percentiles 1-100%; higher percentiles indicate greater diarrhea).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in average weekly bloating symptoms from baseline</measure>
    <time_frame>Week 4, week 8</time_frame>
    <description>To compare the efficacy of PENFS therapy versus sham therapy on the change in average weekly bloating symptoms after 4 weeks of treatment and at extended follow-up (8 weeks) compared to baseline, assessed through the PROMIS Gastrointestinal Gas and Bloating Scale (percentiles 0.1-100%; higher percentiles indicate greater gas and bloating).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in quality of life from baseline</measure>
    <time_frame>Week 4, week 8</time_frame>
    <description>To compare the efficacy of PENFS therapy versus sham therapy on the change in IBS-quality of life (IBS-QOL) in adult patients with IBS after 4 weeks of treatment and at extended follow-up (8 weeks) compared to baseline. IBS QOL will be assessed on a scale from 0-100, with higher scores indicating better IBS specific quality of life.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in heart rate variability from baseline</measure>
    <time_frame>Week 4</time_frame>
    <description>To compare the change in resting cardio-autonomic tone, i.e. heart rate variability (HRV), at baseline and after 4 weeks of treatment in responders vs. non-responders in adult patients with IBS.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of treatment-related adverse events as assessed by a weekly adverse events questionnaire</measure>
    <time_frame>Week 4</time_frame>
    <description>To compare the incidence of treatment-related adverse events from PENFS therapy versus sham therapy in adult patients with IBS. Adverse events will be assessed by a weekly adverse events questionnaire that determines the severity of the adverse event, the relationship to the study intervention, the action taken regarding the study intervention, the outcome of the adverse event, whether or not the adverse event was expected, and if the event was considered a serious adverse event (SAE).</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">54</enrollment>
  <condition>Irritable Bowel Syndrome</condition>
  <condition>Abdominal Pain</condition>
  <condition>Autonomic Nervous System Imbalance</condition>
  <arm_group>
    <arm_group_label>Peripheral Electrical Nerve Field Stimulation (PENFS) Device</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>The PENFS device has a battery activated generator and wire harness. Four leads are attached to the generator, each with a sterile 2 mm, titanium needle. The patient's ear is trans-illuminated to identify neurovascular bundles that are avoided during needle placement. The generator is attached with adhesive to the skin behind the patient's ear. Needles are inserted into the dorsal and ventral aspects of the ear, within 1-1.5 mm of the vascular branches to create a field effect. The device settings are standardized and deliver 3.2 volts with alternating frequencies (1 ms pulses of 1 Hz and 10 Hz) every 2 s. This stimulation targets central pain pathways through branches of cranial nerves V, VII, IX, and X, which innervate the external ear. The device is worn for 5 days/week for a total of 4 weeks. Patients remove devices at home on day 6 of each treatment cycle. Patients will be asked to wear a SmartWatch during the study to monitor heart rate.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Sham Device</arm_group_label>
    <arm_group_type>Sham Comparator</arm_group_type>
    <description>The sham devices will be identical to the active devices but will not administer electrical charges. Per manufacturer design and patient anecdotal experience from previous studies, both active stimulation and sham are below detectable sensation threshold. Per report from previous studies, some patients may experience a sensation around the ear after percutaneous needle placement; however, this sensation can occur with equal likelihood in the active or sham device. The device is worn for 5 days a week for a total of 4 weeks. Patients remove devices at home on day 6 of each treatment cycle. Patients will also be asked to wear a SmartWatch as above.</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Peripheral Electrical Nerve Field Stimulation (PENFS) Device</intervention_name>
    <description>Patients will complete daily worst abdominal pain and bowel habit questionnaires for 1 week prior to initial PENFS device placement to provide a baseline. At visit 1, patients will complete the Bowel Symptom Questionnaire, IBS Symptom Severity Scale (IBS-SSS), PROMIS Belly Pain Scale, Gas and Bloating, Constipation, and Diarrhea Scales, Hospital Anxiety and Depression Scale, and Visceral Sensitivity Index, heart rate variability will be measured, and they will have the initial PENFS device placed. Patients will complete daily worst abdominal pain (scale 0-10) questionnaires throughout the duration of the study. They will return every 7 days for a total of 4 visits for device replacement and additional questionnaires, including the IBS-SSS. Four devices will be placed in total (start of weeks 1, 2, 3, and 4). Stimulation time is 5 days/week during each of the 4 consecutive weeks. Additional questionnaires will be completed at the end of week 4 and at extended follow-up (8 weeks).</description>
    <arm_group_label>Peripheral Electrical Nerve Field Stimulation (PENFS) Device</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Sham Device</intervention_name>
    <description>Patients will complete daily worst abdominal pain and bowel habit questionnaires for 1 week prior to initial sham device placement to provide a baseline. At visit 1, patients will complete the Bowel Symptom Questionnaire, IBS Symptom Severity Scale (IBS-SSS), PROMIS Belly Pain Scale, Gas and Bloating, Constipation, and Diarrhea Scales, Hospital Anxiety and Depression Scale, and Visceral Sensitivity Index, heart rate variability will be measured, and they will have the initial sham device placed. Patients will complete daily worst abdominal pain (scale 0-10) questionnaires throughout the duration of the study. They will return every 7 days for a total of 4 visits for device replacement and additional questionnaires, including the IBS-SSS. Four devices will be placed in total (start of weeks 1, 2, 3, and 4). Stimulation time is 5 days/week during each of the 4 consecutive weeks. Additional questionnaires will be completed at the end of week 4 and at extended follow-up (8 weeks).</description>
    <arm_group_label>Sham Device</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Adults, aged 18-60 years, who are able to provide written, informed consent.&#xD;
&#xD;
          -  Patients must meet Rome IV criteria for IBS, confirmed by a gastroenterologist who&#xD;
             specializes in functional GI disorders. Any of the IBS bowel habit subtypes (diarrhea,&#xD;
             constipation, mixed bowel habits, unclassified) will be allowed.&#xD;
&#xD;
          -  Average daily worst abdominal pain score between 4 and 8 (on a 0-10-point rating&#xD;
             scale).&#xD;
&#xD;
          -  Minimum of 2 days of abdominal pain/week prior to starting trial.&#xD;
&#xD;
          -  At least moderate IBS symptom severity with an IBS-SSS of at least 175 (total score&#xD;
             range 0-500).&#xD;
&#xD;
          -  If receiving pharmacologic therapy for abdominal pain associated with IBS, doses must&#xD;
             be stable for at least 60 days prior to enrollment in the trial.&#xD;
&#xD;
          -  If receiving pharmacologic therapy for IBS that does not have an effect on abdominal&#xD;
             pain, doses must be stable for at least 30 days prior to enrollment in the trial.&#xD;
&#xD;
        Mandatory Exclusion Criteria:&#xD;
&#xD;
          -  Patients under the age of 18 years or over the age of 60 years&#xD;
&#xD;
          -  Patients who cannot provide informed consent or do not speak English&#xD;
&#xD;
          -  Co-morbid, organic medical conditions associated with abdominal pain, including:&#xD;
             Inflammatory bowel disease, chronic liver disease, peptic ulcer disease, celiac&#xD;
             disease, diverticulitis, appendicitis, colorectal cancer, endometriosis, pregnancy,&#xD;
             other intestinal or extra-intestinal malignancies. Patients with overlapping&#xD;
             functional GI disorders (i.e. functional dyspepsia) will not be excluded as long as&#xD;
             IBS is their predominant disorder&#xD;
&#xD;
          -  History of surgery involving CN V, VII, IX, or X.&#xD;
&#xD;
          -  History of abdominal surgeries other than appendectomy or cholecystectomy at least 6&#xD;
             months before entry into trial.&#xD;
&#xD;
          -  Patients on chronic opioids, benzodiazepines, or with illicit substance use&#xD;
&#xD;
          -  Patients with underlying neurologic conditions, including history of: seizures, CVA,&#xD;
             uncontrolled migraines, traumatic brain injury, multiple sclerosis&#xD;
&#xD;
          -  Patients with underlying psychiatric conditions&#xD;
&#xD;
          -  Patients with dermatologic conditions affecting the ear, face, or neck region (i.e.&#xD;
             psoriasis), or with cuts or abrasions to the external ear that would interfere with&#xD;
             needle placement&#xD;
&#xD;
          -  Patients with hemophilia or other bleeding disorders&#xD;
&#xD;
          -  Patients with any implanted electrical device&#xD;
&#xD;
          -  Patients who are pregnant or breastfeeding&#xD;
&#xD;
        Preferred, but not mandatory, exclusion criteria:&#xD;
&#xD;
          -  Movement disorder&#xD;
&#xD;
          -  Unwillingness to wear the SmartWatch on upper extremity (left or right wrist)&#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>Lin Chang, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of California, Los Angeles</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Jessica Sohn</last_name>
    <phone>310-206-1656</phone>
    <email>JessicaSohn@mednet.ucla.edu</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Lin Chang, MD</last_name>
    <phone>310-206-1656</phone>
    <email>LinChang@mednet.ucla.edu</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>UCLA</name>
      <address>
        <city>Los Angeles</city>
        <state>California</state>
        <zip>90095</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Jessica Sohn</last_name>
      <phone>310-206-1656</phone>
      <email>JessicaSohn@mednet.ucla.edu</email>
    </contact>
    <investigator>
      <last_name>Lin Chang, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <reference>
    <citation>Kovacic K, Hainsworth K, Sood M, Chelimsky G, Unteutsch R, Nugent M, Simpson P, Miranda A. Neurostimulation for abdominal pain-related functional gastrointestinal disorders in adolescents: a randomised, double-blind, sham-controlled trial. Lancet Gastroenterol Hepatol. 2017 Oct;2(10):727-737. doi: 10.1016/S2468-1253(17)30253-4. Epub 2017 Aug 18.</citation>
    <PMID>28826627</PMID>
  </reference>
  <reference>
    <citation>Krasaelap A, Sood MR, Li BUK, Unteutsch R, Yan K, Nugent M, Simpson P, Kovacic K. Efficacy of Auricular Neurostimulation in Adolescents With Irritable Bowel Syndrome in a Randomized, Double-Blind Trial. Clin Gastroenterol Hepatol. 2020 Aug;18(9):1987-1994.e2. doi: 10.1016/j.cgh.2019.10.012. Epub 2019 Oct 14.</citation>
    <PMID>31622740</PMID>
  </reference>
  <verification_date>January 2023</verification_date>
  <study_first_submitted>May 28, 2020</study_first_submitted>
  <study_first_submitted_qc>June 9, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 11, 2020</study_first_posted>
  <last_update_submitted>January 9, 2023</last_update_submitted>
  <last_update_submitted_qc>January 9, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">January 11, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of California, Los Angeles</investigator_affiliation>
    <investigator_full_name>Lin Chang, MD</investigator_full_name>
    <investigator_title>Vice-Chief, Vatche and Tamar Manoukian Division of Digestive Diseases, Program Director, UCLA GI Fellowship Program, Co-Director, G. Oppenheimer Center for Neurobiology of Stress and Resilience</investigator_title>
  </responsible_party>
  <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>Abdominal Pain</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT04428619
org study id: IRB# 19-001796
nct id: NCT04428619
lead sponsor: 
collaborator: 
is fda regulated drug: No
is fda regulated device: Yes
is us export: No
This is a prospective, double-blind, randomized, sham-controlled pilot study evaluating the
      efficacy of percutaneous electrical nerve field stimulation for the treatment of adult
      patients with irritable bowel syndrome (IBS).
IBS has a worldwide prevalence around 11% and is characterized by chronic or recurrent
      abdominal pain associated with altered bowel habits. Abnormalities within the brain-gut axis,
      visceral hypersensitivity, and dysfunction of the autonomic nervous system are important
      components contributing to the pathophysiology of IBS. Despite recent advances in medical
      therapies for IBS, a significant subgroup of patients fails to experience satisfactory relief
      of abdominal pain. Given evidence of anti-inflammatory and anti-nociceptive components of
      vagal nerve pathways, peripheral field stimulation of the vagus nerve may help reduce
      abdominal pain in patients with IBS.

      Percutaneous electrical nerve field stimulation (PENFS) administered via the IB-Stim device
      (Innovative Health Solutions, Versailles, IN, USA) has been shown to be efficacious in
      adolescent patients with abdominal-pain-related functional GI disorders, including IBS. This
      device uses discontinuous frequencies of stimulation to target central pain pathways through
      branches of cranial nerves V, VII, IX, and X that innervate the external ear and project to
      certain brainstem nuclei, including the nucleus tractus solitarius (NTS). The NTS then acts
      as a relay station to other brain areas involved in pain modulation and autonomic control,
      including the rostral ventral medulla, locus coeruleus, hypothalamus, and amygdala. In
      adolescent studies, PENFS was associated with a greater reduction in worst abdominal pain and
      composite abdominal pain scores from baseline as well as compared with a sham device after
      three weeks of treatment. These effects were sustained over an extended follow-up period with
      minimal to no side effects. In addition, a greater proportion of adolescents in the PENFS arm
      achieved at least a 30% reduction in worst abdominal pain scores from baseline after 3 weeks
      of treatment.

      The IB-Stim is the first device to be approved by the Food and Drug Administration (FDA) for
      the treatment of functional abdominal pain in adolescents aged 11-18 with IBS. However, the
      efficacy of PENFS in adults with IBS is not currently known. This study is a double-blind,
      randomized, sham-controlled pilot study evaluating the efficacy of PENFS using IB-Stim for
      the treatment of IBS symptoms in adult patients with IBS.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Single (Investigator)
masking description: Patients who meet study eligibility criteria will be randomly assigned (1:1) in blocks of two and four, using a code generated by a randomization program to 4 weeks of stimulation with an active or inactive (sham) PENFS device. Per manufacturer design, both active stimulation and sham are below a detectable sensation threshold. Allocation will be concealed, and all physicians, statisticians, participants, and research coordinators will be unaware of device codes. One research coordinator who has no patient contact will be unblinded and handle allocation and storage of devices. At the end of 4 weeks, patients will be asked to which device arm they believe they were randomized.
measure: Mean change in IBS symptom severity from baseline
time frame: Week 4
description: To compare the efficacy of PENFS therapy versus sham therapy on the change in IBS symptom severity in adult IBS patients after 4 weeks of treatment, assessed through a mean change in the IBS-SSS.
measure: Mean change in IBS symptom severity from baseline
time frame: Week 8
description: To compare the efficacy of PENFS therapy versus sham therapy on the change in IBS symptom severity in adult IBS patients at extended follow-up (8 weeks), assessed through a mean change in the IBS-SSS.
measure: IBS symptom severity responder rate
time frame: Week 4
description: To compare the efficacy of PENFS therapy versus sham therapy on the change in IBS symptom severity in adult IBS patients after 4 weeks of treatment compared to baseline. Participants will be considered responders if there is at least a 50-point reduction on the IBS-SSS.
measure: Daily worst abdominal pain responder rate
time frame: Week 4
description: To compare the proportion of adult patients with IBS who experience a change of ≥ 30% from baseline in average daily worst abdominal pain scores after 4 weeks of treatment (measured using a validated, 11-point numeric rating scale). Participants who have a reduction in daily worst abdominal pain scores of ≥ 30% from baseline will be considered clinical responders.
measure: Mean change in average daily worst abdominal pain from baseline
time frame: Week 4
description: To compare the efficacy of PENFS therapy versus sham therapy on mean worst daily abdominal pain scores after 4 weeks compared to baseline in adult patients with IBS
measure: Change in average weekly abdominal pain symptoms from baseline
time frame: Week 4, week 8
description: To compare the efficacy of PENFS therapy versus sham therapy on the change in average weekly abdominal pain symptoms after 4 weeks of treatment and at extended follow-up (8 weeks) compared to baseline, assessed through the PROMIS Gastrointestinal Belly Pain Scale (percentiles 2-100%; higher percentiles indicate worse abdominal pain).
measure: Change in average daily stool consistency from baseline
time frame: Week 4
description: To compare the efficacy of PENFS therapy versus sham therapy on the change in average daily stool consistency after 4 weeks of treatment compared to baseline, assessed using the Bristol Stool Form Scale (BSFS) (stool types 1-7; types 1 and 2 indicate constipation, types 3 and 4 are normal consistency stools, type 5 indicates stool lacking fiber, types 6 and 7 indicate diarrhea).
measure: Change in average weekly bowel habits from baseline
time frame: Week 4, week 8
description: To compare the efficacy of PENFS therapy versus sham therapy on the change in average weekly bowel habits after 4 weeks of treatment and at extended follow-up (8 weeks) compared to baseline, assessed through the PROMIS Gastrointestinal Constipation Scale (percentiles 0.3-100%; higher percentiles indicate greater constipation) and Gastrointestinal Diarrhea Scale (percentiles 1-100%; higher percentiles indicate greater diarrhea).
measure: Change in average weekly bloating symptoms from baseline
time frame: Week 4, week 8
description: To compare the efficacy of PENFS therapy versus sham therapy on the change in average weekly bloating symptoms after 4 weeks of treatment and at extended follow-up (8 weeks) compared to baseline, assessed through the PROMIS Gastrointestinal Gas and Bloating Scale (percentiles 0.1-100%; higher percentiles indicate greater gas and bloating).
measure: Change in quality of life from baseline
time frame: Week 4, week 8
description: To compare the efficacy of PENFS therapy versus sham therapy on the change in IBS-quality of life (IBS-QOL) in adult patients with IBS after 4 weeks of treatment and at extended follow-up (8 weeks) compared to baseline. IBS QOL will be assessed on a scale from 0-100, with higher scores indicating better IBS specific quality of life.
measure: Change in heart rate variability from baseline
time frame: Week 4
description: To compare the change in resting cardio-autonomic tone, i.e. heart rate variability (HRV), at baseline and after 4 weeks of treatment in responders vs. non-responders in adult patients with IBS.
measure: Incidence of treatment-related adverse events as assessed by a weekly adverse events questionnaire
time frame: Week 4
description: To compare the incidence of treatment-related adverse events from PENFS therapy versus sham therapy in adult patients with IBS. Adverse events will be assessed by a weekly adverse events questionnaire that determines the severity of the adverse event, the relationship to the study intervention, the action taken regarding the study intervention, the outcome of the adverse event, whether or not the adverse event was expected, and if the event was considered a serious adverse event (SAE).
arm group label: Peripheral Electrical Nerve Field Stimulation (PENFS) Device
arm group type: Active Comparator
description: The PENFS device has a battery activated generator and wire harness. Four leads are attached to the generator, each with a sterile 2 mm, titanium needle. The patient's ear is trans-illuminated to identify neurovascular bundles that are avoided during needle placement. The generator is attached with adhesive to the skin behind the patient's ear. Needles are inserted into the dorsal and ventral aspects of the ear, within 1-1.5 mm of the vascular branches to create a field effect. The device settings are standardized and deliver 3.2 volts with alternating frequencies (1 ms pulses of 1 Hz and 10 Hz) every 2 s. This stimulation targets central pain pathways through branches of cranial nerves V, VII, IX, and X, which innervate the external ear. The device is worn for 5 days/week for a total of 4 weeks. Patients remove devices at home on day 6 of each treatment cycle. Patients will be asked to wear a SmartWatch during the study to monitor heart rate.
arm group label: Sham Device
arm group type: Sham Comparator
description: The sham devices will be identical to the active devices but will not administer electrical charges. Per manufacturer design and patient anecdotal experience from previous studies, both active stimulation and sham are below detectable sensation threshold. Per report from previous studies, some patients may experience a sensation around the ear after percutaneous needle placement; however, this sensation can occur with equal likelihood in the active or sham device. The device is worn for 5 days a week for a total of 4 weeks. Patients remove devices at home on day 6 of each treatment cycle. Patients will also be asked to wear a SmartWatch as above.
intervention type: Device
intervention name: Peripheral Electrical Nerve Field Stimulation (PENFS) Device
description: Patients will complete daily worst abdominal pain and bowel habit questionnaires for 1 week prior to initial PENFS device placement to provide a baseline. At visit 1, patients will complete the Bowel Symptom Questionnaire, IBS Symptom Severity Scale (IBS-SSS), PROMIS Belly Pain Scale, Gas and Bloating, Constipation, and Diarrhea Scales, Hospital Anxiety and Depression Scale, and Visceral Sensitivity Index, heart rate variability will be measured, and they will have the initial PENFS device placed. Patients will complete daily worst abdominal pain (scale 0-10) questionnaires throughout the duration of the study. They will return every 7 days for a total of 4 visits for device replacement and additional questionnaires, including the IBS-SSS. Four devices will be placed in total (start of weeks 1, 2, 3, and 4). Stimulation time is 5 days/week during each of the 4 consecutive weeks. Additional questionnaires will be completed at the end of week 4 and at extended follow-up (8 weeks).
arm group label: Peripheral Electrical Nerve Field Stimulation (PENFS) Device
intervention type: Device
intervention name: Sham Device
description: Patients will complete daily worst abdominal pain and bowel habit questionnaires for 1 week prior to initial sham device placement to provide a baseline. At visit 1, patients will complete the Bowel Symptom Questionnaire, IBS Symptom Severity Scale (IBS-SSS), PROMIS Belly Pain Scale, Gas and Bloating, Constipation, and Diarrhea Scales, Hospital Anxiety and Depression Scale, and Visceral Sensitivity Index, heart rate variability will be measured, and they will have the initial sham device placed. Patients will complete daily worst abdominal pain (scale 0-10) questionnaires throughout the duration of the study. They will return every 7 days for a total of 4 visits for device replacement and additional questionnaires, including the IBS-SSS. Four devices will be placed in total (start of weeks 1, 2, 3, and 4). Stimulation time is 5 days/week during each of the 4 consecutive weeks. Additional questionnaires will be completed at the end of week 4 and at extended follow-up (8 weeks).
arm group label: Sham Device
criteria: 
gender: All
minimum age: 18 Years
maximum age: 60 Years
healthy volunteers: No
last name: Lin Chang, MD
role: Principal Investigator
affiliation: University of California, Los Angeles
last name: Jessica Sohn
phone: 310-206-1656
email: JessicaSohn@mednet.ucla.edu
last name: Lin Chang, MD
phone: 310-206-1656
email: LinChang@mednet.ucla.edu
facility: 
status: Recruiting
contact: 
investigator: 
country: United States
citation: Kovacic K, Hainsworth K, Sood M, Chelimsky G, Unteutsch R, Nugent M, Simpson P, Miranda A. Neurostimulation for abdominal pain-related functional gastrointestinal disorders in adolescents: a randomised, double-blind, sham-controlled trial. Lancet Gastroenterol Hepatol. 2017 Oct;2(10):727-737. doi: 10.1016/S2468-1253(17)30253-4. Epub 2017 Aug 18.
PMID: 28826627
citation: Krasaelap A, Sood MR, Li BUK, Unteutsch R, Yan K, Nugent M, Simpson P, Kovacic K. Efficacy of Auricular Neurostimulation in Adolescents With Irritable Bowel Syndrome in a Randomized, Double-Blind Trial. Clin Gastroenterol Hepatol. 2020 Aug;18(9):1987-1994.e2. doi: 10.1016/j.cgh.2019.10.012. Epub 2019 Oct 14.
PMID: 31622740
responsible party type: Principal Investigator
investigator affiliation: University of California, Los Angeles
investigator full name: Lin Chang, MD
investigator title: Vice-Chief, Vatche and Tamar Manoukian Division of Digestive Diseases, Program Director, UCLA GI Fellowship Program, Co-Director, G. Oppenheimer Center for Neurobiology of Stress and Resilience
mesh term: Irritable Bowel Syndrome
mesh term: Syndrome
mesh term: Abdominal Pain
sharing ipd: No