Effect of Tenapanor on gut health in patients with constipation-related IBS

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

This study is testing if taking tenapanor for eight weeks can improve gut health in people with constipation-related IBS.

Quick facts

• Phase: Phase 4
• Study type: Interventional
• Enrollment: 30 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: Massachusetts General Hospital (Academic / other)
• Drugs / interventions: radiation
• Locations: 1 site (Boston, Massachusetts)
• Trial ID: NCT05995899 on ClinicalTrials.gov

What this trial studies

This study investigates how tenapanor, an FDA-approved medication for irritable bowel syndrome with constipation (IBS-C), influences the gut microbiome and metabolic processes in affected patients. Participants will take tenapanor twice daily for eight weeks while providing stool samples at the four and eight-week marks to assess changes in their gut health. The study aims to build on previous findings that showed tenapanor can increase bowel movements and reduce abdominal pain in IBS-C patients.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18-75 with a BMI between 18.5 and 35 who meet the Rome IV criteria for IBS-C.

Not a fit: Patients with a history of diarrhea-predominant IBS or those who have previously used tenapanor may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could provide insights into how tenapanor improves gut health and symptom management for patients with IBS-C.

How similar studies have performed: Previous studies have shown positive outcomes with tenapanor in IBS-C, indicating a promising approach for this condition.

Eligibility criteria

Inclusion Criteria:

1. Ages 18-75 years old
2. BMI \>18.5 and \<35 kg/m2
3. Rome IV criteria for IBS-C for at least 6 months
4. Compliant with baseline stool submission prior to initiation of medication
5. Ability to follow verbal and written instructions
6. Ability to record daily bowel habits, including frequency, stool consistency (BSFS), and symptom severity
7. Willingness to avoid major dietary changes and use of probiotics during the study period
8. Informed consent form signed by the subjects

Exclusion Criteria:

1. History of loose stools
2. History of irritable bowel syndrome with diarrhea (IBS-D) or mixed irritable bowel syndrome (IBS-M)
3. Non-compliance with baseline stool submission
4. Previous use of tenapanor
5. GI motility obstruction or GI tract structural abnormality
6. Current use of prescribed or illicit opioids
7. History of pelvic floor dysfunction
8. Need for manual maneuvers in order to achieve a BM
9. History of GI lumen surgery at any time or other GI or abdominal operations within 60 days prior to entry into the study
10. History of high-dose stimulative or cathartic laxative abuse as judged by investigator team
11. Severe IBS-C as judged by the investigator
12. Neurological disorders, metabolic disorders, or other significant disease that would impair their ability to participate in the study
13. Cardiovascular disease, diabetes, cancer, Crohn's disease, ulcerative colitis
14. BMI of \<18.5 or \>35 kg/m2
15. Pregnancy (or positive serum or urine pregnancy test(s) in females of childbearing potential) or lactation
16. Absence of contraception in females of childbearing potential
17. History of allergic reaction to tenapanor
18. Administration of other FDA-approved agents for the treatment of IBS-C within 1 month prior to Screening Visit:

    * Linaclotide
    * Lubiprostone
    * Plecanatide
19. If treated with any of the following medications, dosing (or approximate frequency of 'as needed' use) must be stable for at least 30 days prior to Screening Visit and the subject must agree to maintain the same dose (or approximate frequency of 'as needed' use) or a decreased dose of medication throughout the study:

    * Probiotics
    * Bulk laxatives, fiber, and stool softeners
20. Exclusion of colonic inertia with symptoms of \< 1 BM per 2 weeks
21. Subjects anticipating surgical intervention during the study
22. Known history of diabetes (type 1 or 2)
23. Subjects with recent antibiotic use (last 3 months) or anticipated antibiotic use during the study period
24. History of inflammatory bowel disease
25. Supine SBP \> 160 mm Hg and/or supine DBP \> 95 mm Hg (mean of two consecutive readings)
26. Angina, coronary bypass, or myocardial infarction within 6 months prior to Screening Visit
27. History of swallowing disorders
28. History of gastric bypass or any other gastric surgery
29. History of small bowel resection (except if related to appendectomy)
30. History of gastric or duodenal ulcer
31. History of gastroparesis
32. History of abdominal radiation treatment
33. History of pancreatitis
34. History of intestinal stricture (e.g., Crohn's disease)
35. History of intestinal obstruction or subjects at high risk of intestinal obstruction including suspected small bowel adhesions
36. History of malabsorption
37. History of hepatitis B or C
38. History of human immunodeficiency virus
39. History of cancer within the past 5 years (except adequately-treated localized basal cell skin cancer or in situ uterine cervical cancer)
40. Any other clinically significant disease interfering with the assessments of tenapanor, according to the Investigator (e.g., disease requiring corrective treatment, potentially leading to study discontinuation)
41. HbA1c \> 8.5% (\> 69 mmol/mol)

43. Any relevant biochemical abnormality interfering with the assessments of tenapanor, according to the Investigator 44. Antidiabetic medications within 1 month prior to Screening Visit (except stable dose of metformin, ≤ 1500 mg/day, for at least 1 month in subjects with type 2 diabetes) 45. Medications requiring mandatory administration twice per day with meals

Where this trial is running

Boston, Massachusetts

• Massachusetts General Hospital — Boston, Massachusetts, United States (Recruiting)

Study contacts

• Study coordinator: Annie Zhu

Conditions IBS; IBS - Irritable Bowel Syndrome