Ignite Creation Date:
2024-05-06 @ 8:18 PM
Last Modification Date:
2024-10-26 @ 3:24 PM
Study NCT ID:
NCT06326645
Status:
NOT_YET_RECRUITING
Last Update Posted:
2024-03-22
First Post:
2023-11-25
Brief Title:
Open-Label Pilot Study With Crofelemer in Patients With Short Bowel Syndrome
Sponsor:
Lindsey Russell MD
Organization:
The Cleveland Clinic
Study Overview
Official Title:
Open-Label Pilot Study With Crofelemer in Patients With Short Bowel Syndrome
Status:
NOT_YET_RECRUITING
Status Verified Date:
2024-03
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief 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
Detailed Description:
Short bowel syndrome SBS is defined as less than 200 cm in adults of remaining small bowel ie 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 andor 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 Diphenoxylateatropine 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 andor 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
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 andor 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 Diphenoxylateatropine 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 andor 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
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
False
Is an FDA AA801 Violation?:
None