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?

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. .

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.

How does the drug Crofelemer differ from other treatments for short bowel syndrome?

Crofelemer is unique because it is primarily used to manage diarrhea by regulating fluid secretion in the intestines, which may help in conditions like short bowel syndrome where fluid balance is crucial. Unlike other treatments that focus on promoting intestinal growth or adaptation, Crofelemer's mechanism targets the symptoms directly. ^{1 2 3 4 5}

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

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]

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]

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]

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]

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]

Citations

1. United Arab Emirates pubmed.ncbi.nlm.nih.gov

Designing Novel Teduglutide Analogues with Improved Binding Affinity: An In Silico Peptide Engineering Approach. [2021]

2. United States 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. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

Glucagon-like peptide-2 analogues for Crohn's disease patients with short bowel syndrome and intestinal failure. [2022]

4. France pubmed.ncbi.nlm.nih.gov

[Use of oral drugs and short bowel syndrome: an analysis of practices]. [2015]

5. England pubmed.ncbi.nlm.nih.gov

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