Open-Label Pilot Study With Crofelemer in Patients With Short Bowel Syndrome

Short Bowel Syndrome Clinical Trial

Official title: Open-Label Pilot Study With Crofelemer in Patients With Short Bowel Syndrome

Status Not yet recruiting

Clinical Trial Summary

The objectives of this study are to evaluate the efficacy and safety of crofelemer treatment in adults affected by Short Bowel Syndrome (SBS) with an ileostomy on parenteral support (PS) in reducing output or PS needs. Crofelemer will be provided as a powder three times daily for 12 weeks and a 4 week follow up. .

Clinical Trial Description

Short bowel syndrome (SBS) is defined as less than 200 cm in adults of remaining small bowel (i.e. excluding colon) in continuity leading to the need for nutritional and fluid supplements due to impaired absorption of nutrients, electrolytes and fluids.

Most patients with SBS experience debilitating diarrhea that severely hinders their health outcomes and quality of life. SBS-associated diarrhea may have several etiologies including excessive secretion and/or impaired absorption of fluid and electrolytes across the intestinal epithelium. Diarrhea can lead to dehydration, electrolyte imbalance, protein-calorie malnutrition, and loss of critical vitamins and minerals. Consequently, diarrhea in SBS can be severe and life-threatening without proper treatment.

The aggressive use of anti-diarrheal medications in SBS are often clinically required to help manage symptoms. Anti- Secretory agents, including proton pump inhibitors, histamin-2 receptor agonists and somatostatin analogue (Octreotide) as well as various anti-motility agents, including loperamide, Diphenoxylate/atropine, and opioids (Codeine, Tincture of Opium), are often used in higher doses and various formulations with varying effects in patients to help control the diarrhea. Overall, the management of diarrhea is challenging requiring multidisciplinary teams and improved therapies are needed.

Parenteral Nutrition (PN) is a life-saving therapy for patients unable to meet nutritional needs by mouth and a recent study noted that SBS is the most common indication for home PN in the US. However, long-term PN is associated with experience serious metabolic complications, including hepatic and biliary disorders manifested by steatosis, fibrosis and cholestasis. Other complications include central line infections and decrease in quality of life. This has garnered orphan drug designation for intestinotrophic hormones like the glucagon-like peptide-2 (GLP-2) analogue, teduglutide (Gattex), which increases intestinal and portal blood flow, inhibits gastric acid secretion, and decreases intestinal motility, leading up to 20% decrease in PN provisions with treatment in patients with SBS. However, these agents can take weeks to months to take effect and is associated with known risk of developing intestinal growths and cancer that require ongoing surveillance with screening endoscopy. There is a need for other medications to help in the treatment of SBS.

Crofelemer is a novel anti-diarrheal drug that reduces intestinal chloride ion and fluid secretion. It is an FDA approved treatment for HIV-diarrhea (MytesiTM). Its anti-diarrheal properties are due to modulation of chloride ion channel secretion by cystic fibrosis transmembrane conductance regulator (CFTR) and/or Ca2+ activated Cl- channel (CaCC).

Crofelemer has been shown to be a dose-dependent, partial antagonism of CFTR and complete inhibition of CaCC without any changes in the intracellular cyclic Adenosin Monophosphate (cAMP) or calcium levels. Crofelemer also does not have any effects on gut motility or peristalsis. It also has been shown to have minimal absorptive capacity, therefore will not interact with other medications and limit serious adverse events.

It is unknown if Crofelemer can be effective in reducing diarrhea in patients with SBS. There have been case reports that suggest beneficial effects on nutritional status and improvement of diarrhea with tablets of Crofelemer in SBS. This study aims to assess the efficacy of Crofelemer in patients with SBS and ileostomy on Parenteral support. ;

Related Conditions & MeSH terms

• Short Bowel Syndrome
• Syndrome

• NCT number: NCT06326645
• Study type: Interventional
• Source: The Cleveland Clinic
• Contact: Kaylyn McClough
• Phone: (216) 444-1122
• Email: mcclouk@ccf.org
• Status: Not yet recruiting
• Phase: Early Phase 1
• Start date: December 1, 2024
• Completion date: December 1, 2025