xml: <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/NCT05995899</url>
    </required_header>
    <id_info>
      <org_study_id>2023P001911</org_study_id>
      <nct_id>NCT05995899</nct_id>
    </id_info>
    <brief_title>Effect of Tenapanor on the Metagenomics and Metabolomics of Patients With Irritable Bowel Syndrome With Constipation</brief_title>
    <official_title>An Open-label, Single Center Investigator Sponsored Study Assessing the Effect of Tenapanor on Metagenomic and Metabolomic Markers in Patients With Irritable Bowel Syndrome With Constipation</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Kyle Staller, MD, MPH</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
      <collaborator>
        <agency>Ardelyx</agency>
        <agency_class>Industry</agency_class>
      </collaborator>
    </sponsors>
    <source>Massachusetts General Hospital</source>
    <oversight_info>
      <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
      <is_fda_regulated_device>No</is_fda_regulated_device>
      <is_us_export>Yes</is_us_export>
    </oversight_info>
    <brief_summary>
      <textblock>
        The aim of this study is to better understand how tenapanor affects the metagenomics and&#xD;
        metabolomics of patients with irritable bowel syndrome with constipation (IBS-C). Tenapanor&#xD;
        is the newest FDA-approved agent for IBS-C. It is a small molecule that inhibits the NHE3&#xD;
        receptor, leading to impaired sodium and water absorption in the intestine. Previous clinical&#xD;
        trials comparing tenapanor to placebo showed that a 50 mg dose of tenapanor led to increased&#xD;
        bowel movements and decreased abdominal pain. This study consists of an 8-week treatment&#xD;
        period in which subjects will ingest one capsule of tenapanor (50 mg per dose), twice daily,&#xD;
        and send in stool samples following 4 weeks and 8 weeks of treatment.&#xD;
      </textblock>
    </brief_summary>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">November 2023</start_date>
    <completion_date type="Anticipated">November 2026</completion_date>
    <primary_completion_date type="Anticipated">November 2026</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>Measuring metagenomics of stool samples using whole genome shotgun sequencing (WGS)</measure>
      <time_frame>Subjects will submit stool samples at 0 weeks, 4 weeks, and 8 weeks following treatment.</time_frame>
      <description>Sequence-based microbial community surveys will be carried out by whole genome shotgun sequencing (WGS) at the Broad Institute using their established sequencing and analysis pipeline for the Illumina HiSeq2000 platform used in Human Microbiome Project (HMP) to characterize rare taxa and understand relationships between community membership and function. Composition analysis of metagenome will be performed using the read-based bioinformatics analysis suite. Functional genomic profiles, detailed species-specific reconstruction of microbial metabolic pathways, their complement of gene orthologs, taxonomic distributions, and abundances will be generated with HUMAnN2. This will provide taxon-specific profiles of UniRef orthologous gene families, MetCyc, UniPathway, and KEGG pathways to survey microbial community metabolite production potential in each metagenome according to tenapanor use.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Measuring metabolomics of stool samples using the DiscoveryHD4TM Platform</measure>
      <time_frame>Subjects will submit stool samples at 0 weeks, 4 weeks, and 8 weeks following treatment.</time_frame>
      <description>Stool samples will also undergo metabolomics profiling at Metabolon Inc using the DiscoveryHD4TM Platform, a comprehensive and well-validated high-throughput metabolomics platform available for clinical and research use. Metabolites are identified by automated comparison of the ion features in the experimental samples to a reference library of ~8,000 chemical standard entries that include retention time, molecular weight (m/z), preferred adducts, in-source fragments and MS spectra, and they are visually curated for quality control using Metabolon software.</description>
    </primary_outcome>
    <number_of_arms>1</number_of_arms>
    <enrollment type="Anticipated">30</enrollment>
    <condition>IBS</condition>
    <condition>IBS - Irritable Bowel Syndrome</condition>
    <arm_group>
      <arm_group_label>Patients with IBS-C</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Tenapanor</intervention_name>
      <description>IBS-C patients will ingest one capsule of tenapanor (50 mg per dose), twice daily, before breakfast and dinner for a total of 8 weeks</description>
      <arm_group_label>Patients with IBS-C</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            1. Ages 18-75 years old&#xD;
  &#xD;
            2. BMI &gt;18.5 and &lt;35 kg/m2&#xD;
  &#xD;
            3. Rome IV criteria for IBS-C for at least 6 months&#xD;
  &#xD;
            4. Compliant with baseline stool submission prior to initiation of medication&#xD;
  &#xD;
            5. Ability to follow verbal and written instructions&#xD;
  &#xD;
            6. Ability to record daily bowel habits, including frequency, stool consistency (BSFS),&#xD;
               and symptom severity&#xD;
  &#xD;
            7. Willingness to avoid major dietary changes and use of probiotics during the study&#xD;
               period&#xD;
  &#xD;
            8. Informed consent form signed by the subjects&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            1. History of loose stools&#xD;
  &#xD;
            2. History of irritable bowel syndrome with diarrhea (IBS-D) or mixed irritable bowel&#xD;
               syndrome (IBS-M)&#xD;
  &#xD;
            3. Non-compliance with baseline stool submission&#xD;
  &#xD;
            4. Previous use of tenapanor&#xD;
  &#xD;
            5. GI motility obstruction or GI tract structural abnormality&#xD;
  &#xD;
            6. Current use of prescribed or illicit opioids&#xD;
  &#xD;
            7. History of pelvic floor dysfunction&#xD;
  &#xD;
            8. Need for manual maneuvers in order to achieve a BM&#xD;
  &#xD;
            9. History of GI lumen surgery at any time or other GI or abdominal operations within 60&#xD;
               days prior to entry into the study&#xD;
  &#xD;
           10. History of high-dose stimulative or cathartic laxative abuse as judged by investigator&#xD;
               team&#xD;
  &#xD;
           11. Severe IBS-C as judged by the investigator&#xD;
  &#xD;
           12. Neurological disorders, metabolic disorders, or other significant disease that would&#xD;
               impair their ability to participate in the study&#xD;
  &#xD;
           13. Cardiovascular disease, diabetes, cancer, Crohn's disease, ulcerative colitis&#xD;
  &#xD;
           14. BMI of &lt;18.5 or &gt;35 kg/m2&#xD;
  &#xD;
           15. Pregnancy (or positive serum or urine pregnancy test(s) in females of childbearing&#xD;
               potential) or lactation&#xD;
  &#xD;
           16. Absence of contraception in females of childbearing potential&#xD;
  &#xD;
           17. History of allergic reaction to tenapanor&#xD;
  &#xD;
           18. Administration of other FDA-approved agents for the treatment of IBS-C within 1 month&#xD;
               prior to Screening Visit:&#xD;
  &#xD;
                 -  Linaclotide&#xD;
  &#xD;
                 -  Lubiprostone&#xD;
  &#xD;
                 -  Plecanatide&#xD;
  &#xD;
           19. If treated with any of the following medications, dosing (or approximate frequency of&#xD;
               'as needed' use) must be stable for at least 30 days prior to Screening Visit and the&#xD;
               subject must agree to maintain the same dose (or approximate frequency of 'as needed'&#xD;
               use) or a decreased dose of medication throughout the study:&#xD;
  &#xD;
                 -  Probiotics&#xD;
  &#xD;
                 -  Bulk laxatives, fiber, and stool softeners&#xD;
  &#xD;
           20. Exclusion of colonic inertia with symptoms of &lt; 1 BM per 2 weeks&#xD;
  &#xD;
           21. Subjects anticipating surgical intervention during the study&#xD;
  &#xD;
           22. Known history of diabetes (type 1 or 2)&#xD;
  &#xD;
           23. Subjects with recent antibiotic use (last 3 months) or anticipated antibiotic use&#xD;
               during the study period&#xD;
  &#xD;
           24. History of inflammatory bowel disease&#xD;
  &#xD;
           25. Supine SBP &gt; 160 mm Hg and/or supine DBP &gt; 95 mm Hg (mean of two consecutive readings)&#xD;
  &#xD;
           26. Angina, coronary bypass, or myocardial infarction within 6 months prior to Screening&#xD;
               Visit&#xD;
  &#xD;
           27. History of swallowing disorders&#xD;
  &#xD;
           28. History of gastric bypass or any other gastric surgery&#xD;
  &#xD;
           29. History of small bowel resection (except if related to appendectomy)&#xD;
  &#xD;
           30. History of gastric or duodenal ulcer&#xD;
  &#xD;
           31. History of gastroparesis&#xD;
  &#xD;
           32. History of abdominal radiation treatment&#xD;
  &#xD;
           33. History of pancreatitis&#xD;
  &#xD;
           34. History of intestinal stricture (e.g., Crohn's disease)&#xD;
  &#xD;
           35. History of intestinal obstruction or subjects at high risk of intestinal obstruction&#xD;
               including suspected small bowel adhesions&#xD;
  &#xD;
           36. History of malabsorption&#xD;
  &#xD;
           37. History of hepatitis B or C&#xD;
  &#xD;
           38. History of human immunodeficiency virus&#xD;
  &#xD;
           39. History of cancer within the past 5 years (except adequately-treated localized basal&#xD;
               cell skin cancer or in situ uterine cervical cancer)&#xD;
  &#xD;
           40. Any other clinically significant disease interfering with the assessments of&#xD;
               tenapanor, according to the Investigator (e.g., disease requiring corrective&#xD;
               treatment, potentially leading to study discontinuation)&#xD;
  &#xD;
           41. HbA1c &gt; 8.5% (&gt; 69 mmol/mol)&#xD;
  &#xD;
          43. Any relevant biochemical abnormality interfering with the assessments of tenapanor,&#xD;
          according to the Investigator 44. Antidiabetic medications within 1 month prior to&#xD;
          Screening Visit (except stable dose of metformin, ≤ 1500 mg/day, for at least 1 month in&#xD;
          subjects with type 2 diabetes) 45. Medications requiring mandatory administration twice per&#xD;
          day with meals&#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_contact>
      <last_name>Annie Zhu</last_name>
      <phone>6177240480</phone>
      <email>azhu13@mgh.harvard.edu</email>
    </overall_contact>
    <overall_contact_backup>
      <last_name>Kyle D. Staller, MD, MPH</last_name>
      <email>kstaller@mgh.harvard.edu</email>
    </overall_contact_backup>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>August 3, 2023</study_first_submitted>
    <study_first_submitted_qc>August 10, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 16, 2023</study_first_posted>
    <last_update_submitted>August 10, 2023</last_update_submitted>
    <last_update_submitted_qc>August 10, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 16, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor-Investigator</responsible_party_type>
      <investigator_affiliation>Massachusetts General Hospital</investigator_affiliation>
      <investigator_full_name>Kyle Staller, MD, MPH</investigator_full_name>
      <investigator_title>Gastroenterology Physician</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>Constipation</mesh_term>
    </condition_browse>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: 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/NCT05995899
  org study id: 2023P001911
  nct id: NCT05995899
  lead sponsor: 
  collaborator: 
  is fda regulated drug: Yes
  is fda regulated device: No
  is us export: Yes
  The aim of this study is to better understand how tenapanor affects the metagenomics and
        metabolomics of patients with irritable bowel syndrome with constipation (IBS-C). Tenapanor
        is the newest FDA-approved agent for IBS-C. It is a small molecule that inhibits the NHE3
        receptor, leading to impaired sodium and water absorption in the intestine. Previous clinical
        trials comparing tenapanor to placebo showed that a 50 mg dose of tenapanor led to increased
        bowel movements and decreased abdominal pain. This study consists of an 8-week treatment
        period in which subjects will ingest one capsule of tenapanor (50 mg per dose), twice daily,
        and send in stool samples following 4 weeks and 8 weeks of treatment.
  allocation: N/A
  intervention model: Single Group Assignment
  primary purpose: Treatment
  masking: None (Open Label)
  measure: Measuring metagenomics of stool samples using whole genome shotgun sequencing (WGS)
  time frame: Subjects will submit stool samples at 0 weeks, 4 weeks, and 8 weeks following treatment.
  description: Sequence-based microbial community surveys will be carried out by whole genome shotgun sequencing (WGS) at the Broad Institute using their established sequencing and analysis pipeline for the Illumina HiSeq2000 platform used in Human Microbiome Project (HMP) to characterize rare taxa and understand relationships between community membership and function. Composition analysis of metagenome will be performed using the read-based bioinformatics analysis suite. Functional genomic profiles, detailed species-specific reconstruction of microbial metabolic pathways, their complement of gene orthologs, taxonomic distributions, and abundances will be generated with HUMAnN2. This will provide taxon-specific profiles of UniRef orthologous gene families, MetCyc, UniPathway, and KEGG pathways to survey microbial community metabolite production potential in each metagenome according to tenapanor use.
  measure: Measuring metabolomics of stool samples using the DiscoveryHD4TM Platform
  time frame: Subjects will submit stool samples at 0 weeks, 4 weeks, and 8 weeks following treatment.
  description: Stool samples will also undergo metabolomics profiling at Metabolon Inc using the DiscoveryHD4TM Platform, a comprehensive and well-validated high-throughput metabolomics platform available for clinical and research use. Metabolites are identified by automated comparison of the ion features in the experimental samples to a reference library of ~8,000 chemical standard entries that include retention time, molecular weight (m/z), preferred adducts, in-source fragments and MS spectra, and they are visually curated for quality control using Metabolon software.
  arm group label: Patients with IBS-C
  arm group type: Experimental
  intervention type: Drug
  intervention name: Tenapanor
  description: IBS-C patients will ingest one capsule of tenapanor (50 mg per dose), twice daily, before breakfast and dinner for a total of 8 weeks
  arm group label: Patients with IBS-C
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: 75 Years
  healthy volunteers: No
  last name: Annie Zhu
  phone: 6177240480
  email: azhu13@mgh.harvard.edu
  last name: Kyle D. Staller, MD, MPH
  email: kstaller@mgh.harvard.edu
  responsible party type: Sponsor-Investigator
  investigator affiliation: Massachusetts General Hospital
  investigator full name: Kyle Staller, MD, MPH
  investigator title: Gastroenterology Physician
  mesh term: Irritable Bowel Syndrome
  mesh term: Syndrome
  mesh term: Constipation