Crofelemer for Short Bowel Syndrome

Overseen By Kaylyn McClough

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: Lindsey Russell, MD

Must not be taking: Immunosuppressants, Biologics, Corticosteroids, others

Disqualifiers: Active infection, Crohn's, IBD, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

Duration: 12 weeks

6 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a treatment called crofelemer to assist individuals with Short Bowel Syndrome (SBS) who require daily IV support for their health. The goal is to determine if crofelemer can reduce the amount of IV support needed. Suitable candidates have had SBS for some time, lack a connected colon, and regularly rely on IV nutrition. Participants will take crofelemer as a powder three times daily for 12 weeks. As an Early Phase 1 trial, this research aims to understand how crofelemer works in people, offering participants the chance to be among the first to receive this new treatment.

Will I have to stop taking my current medications?

The trial requires that certain medications be stable for at least 4 weeks before starting and remain stable during the study. Some medications, like systemic corticosteroids and certain biologics, must not have been used recently. Check with the study team about your specific medications.

Is there any evidence suggesting that crofelemer is likely to be safe for humans?

Previous studies have generally shown that patients tolerate crofelemer well. Research indicates it can help manage symptoms like watery stools and reduce the need for intravenous nutrition in people with conditions similar to Short Bowel Syndrome. So far, no major safety issues have been reported. However, as this trial is in its early stages, gathering complete safety information remains important. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for Short Bowel Syndrome?

Most treatments for Short Bowel Syndrome focus on managing symptoms through dietary adjustments, supplements, or medications like anti-diarrheals and proton pump inhibitors. But Crofelemer works differently, targeting the CFTR protein channels in the intestines to regulate fluid secretion and reduce diarrhea. This unique mechanism of action offers a promising new approach to improving quality of life for patients by directly addressing one of the condition's most challenging symptoms. Researchers are excited about Crofelemer because it could provide a more targeted and effective solution compared to existing therapies.

What evidence suggests that crofelemer might be an effective treatment for Short Bowel Syndrome?

Research has shown that crofelemer, the treatment under study in this trial, might help people with Short Bowel Syndrome (SBS) reduce their need for parenteral nutrition, which involves delivering nutrients through a vein. In earlier studies, crofelemer reduced this nutritional requirement by up to 12.5% in SBS patients. It also decreased stool volume and increased urine output, aiding symptom management. These findings suggest that crofelemer could help manage SBS by lessening the need for parenteral nutrition and improving stool and urine output. ^{1 2 5 6 7}

Who Is on the Research Team?

Lindsey Russell

Principal Investigator

The Cleveland Clinic

Are You a Good Fit for This Trial?

This trial is for adults with Short Bowel Syndrome who have an ileostomy and rely on parenteral support. Participants should be able to take crofelemer powder three times daily for 12 weeks, followed by a 4-week follow-up period.

Inclusion Criteria

It has been over 6 months since my last bowel surgery.

Patients must understand and provide written informed consent before they can participate in the study. They must understand the study procedures of the trial and be willing to complete the required assessments

I do not plan to have surgery to restore function or appearance during the study.

Exclusion Criteria

Alcohol or drug abuse within the last year

I've been hospitalized over four times this past year due to my condition.

I have used teduglutide in the last 3 months.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Crofelemer as a powder three times daily for 12 weeks

12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Crofelemer

Trial Overview

The study tests the effectiveness of crofelemer in reducing intestinal output or the need for parenteral support in SBS patients. Crofelemer is administered orally as a powder, taken three times a day over a course of 12 weeks.

How Is the Trial Designed?

Group I: Crofelemer Group Experimental Treatment 1 Intervention

Who Is Running the Clinical Trial?

Lindsey Russell, MD

Lead Sponsor

Trials

1

Recruited

6+

Napo Pharmaceuticals, Inc.

Industry Sponsor

Trials

6

Recruited

470+

Published Research Related to This Trial

Combining low doses of the GLP-2 receptor agonist h[Gly2]GLP2 with a high dose of the GLP-1 receptor agonist Exendin-4 (Ex4) significantly increased small intestinal weight and length in mice, indicating enhanced intestinal growth, which is crucial for treating short bowel syndrome (SBS).

This combination therapy did not negatively impact body weight, food intake, or glucose homeostasis, suggesting it could be a safe and effective treatment strategy for patients with SBS, improving intestinal function without adverse effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Complementary and antagonistic effects of combined glucagon-like peptide-2 and glucagon-like peptide-1 receptor agonist administration on parameters relevant to short bowel syndrome. Srikrishnaraj, A., Jeong, H., Brubaker, PL.[2022]

Teduglutide, the only FDA-approved treatment for short bowel syndrome, works by binding to the GLP-2 receptor, and this study identified key amino acids that enhance this interaction.

Using computational methods, researchers designed novel analogues of teduglutide with mutations like D15I and D15M, which showed improved binding affinity to the GLP-2 receptor, potentially leading to more effective treatments for short bowel syndrome.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Designing Novel Teduglutide Analogues with Improved Binding Affinity: An In Silico Peptide Engineering Approach. Alizadeh, AA., Dastmalchi, S.[2021]

Glucagon-like peptide-2 analogues, such as teduglutide, have been shown to significantly promote intestinal growth and function in patients with short bowel syndrome and intestinal failure, potentially reducing their reliance on parenteral nutrition.

These treatments are particularly relevant for patients with short bowel syndrome resulting from Crohn's disease, highlighting their therapeutic potential even in the context of advanced medical therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Glucagon-like peptide-2 analogues for Crohn's disease patients with short bowel syndrome and intestinal failure. Pizzoferrato, M., Puca, P., Ennas, S., et al.[2022]

Recent advancements in treating short bowel syndrome (SBS) have highlighted the effectiveness of glucagon-like peptide-2 (GLP-2) analogs, such as teduglutide, glepaglutide, and apraglutide, in promoting intestinal rehabilitation.

High-quality studies have provided strong evidence supporting the use of these GLP-2 analogs, which may enhance intestinal adaptation and improve the ability to maintain oral or enteral nutrition in patients with SBS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An updated overview of glucagon-like peptide-2 analog trophic therapy for short bowel syndrome in adults. Zhu, C., Li, Y.[2022]

In patients with short bowel syndrome (SBS), 79% of medications were prescribed orally, with a notable increase in oral prescriptions for type 3 SBS compared to type 1.

Most drug prescriptions included dietary supplements (29%), gastrointestinal drugs (14.3%), and cardiovascular drugs (11.4%), and dosages generally adhered to standard recommendations, except for gastrointestinal medications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Use of oral drugs and short bowel syndrome: an analysis of practices]. Faye, E., Corcos, O., Bergmann, JF., et al.[2015]

Citations

1.

jaguarhealth.gcs-web.com

jaguarhealth.gcs-web.com/news-releases/news-release-details/proof-concept-results-show-crofelemer-reduced-total-parenteral

Proof-of-Concept Results Show Crofelemer Reduced Total ...

Proof-of-concept results show Crofelemer reduced total parenteral nutrition in patients with rare diseases Microvillus Inclusion Disease (MVID) and Short Bowel ...

2.

clinicaltrials.gov

clinicaltrials.gov/study/NCT06904872?term=CROFELEMER&viewType=Table&rank=5

Safety and Efficacy of Crofelemer in Adult Patients With ...

A 24-week, randomized, placebo-controlled, double-blind study to evaluate the efficacy, safety and tolerability of crofelemer in patients with Short Bowel ...

3.

biospace.com

biospace.com/press-releases/jaguar-health-provides-updates-on-orphan-disease-intestinal-failure-development-program-for-crofelemer

Jaguar Health Provides Updates on Orphan Disease ...

Crofelemer reduced the required total parenteral nutrition in patients with intestinal failure due to MVID and short bowel syndrome by up to 27% and 12.5% ...

4.

finance.yahoo.com

finance.yahoo.com/news/proof-concept-results-show-jaguar-130000907.html

Proof-of-Concept Results Show Jaguar Health's ...

In addition, this data showed that crofelemer reduced stool volume output and/or frequency of watery stools, and increased urine output - an ...

5.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC6970555/

Randomized Clinical Trial: Crofelemer Treatment in Women ...

The primary efficacy endpoint was overall change in percentage of abdominal pain/discomfort-free days. Post hoc analysis for Food and Drug Administration (FDA) ...

6.

trialx.com

trialx.com/clinical-trials/listings/319783/safety-and-efficacy-of-crofelemer-in-adult-patients-with-short-bowel-syndrome-and-intestinal-failure-sbs-if-without-colon-in-continuity-cic/

Safety and Efficacy of Crofelemer in ...

This is a 24-week, randomized, placebo-controlled, double-blind study to evaluate the efficacy, safety and tolerability of crofelemer in ...

7.

clinicaltrials.gov

clinicaltrials.gov/study/NCT06326645?cond=%22Short%2Bbowel%2Bsyndrome%22&viewType=Table&rank=5

Open-Label Pilot Study With Crofelemer in Patients With Short ...

See Delay Results Type in the Results Data ... The disease, disorder, syndrome ... Safety continues to be evaluated, and short-term adverse events are studied.