Microbiota Transplant Therapy for Sclerosing Cholangitis

Overseen By Amanda Kabage

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: University of Minnesota

Must be taking: UDCA, azathioprine

Must not be taking: Antibiotics, obeticholic acid

Disqualifiers: Advanced PSC, Viral hepatitis, Cirrhosis, Pregnancy, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 31 weeks

28 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment called microbiota transplant therapy (MTT) for individuals with primary sclerosing cholangitis (PSC), a liver disease affecting the bile ducts. The goal is to determine if this therapy is safe and practical as a treatment option. Participants must have a PSC diagnosis and no advanced complications such as liver cirrhosis. As an Early Phase 1 trial, this research aims to understand how this new treatment works in people, offering participants the opportunity to be among the first to receive this innovative therapy.

Will I have to stop taking my current medications?

You can continue taking your current medications during the trial, except for obeticholic acid or other experimental therapies for PSC, which require a 3-month break before starting the trial.

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

Research shows that microbiota transplant therapy (MTT) is generally safe, but its use for primary sclerosing cholangitis (PSC) is still being explored. Previous studies have examined MTT's role in restoring healthy gut bacteria. These studies usually find that MTT is well-tolerated, with only mild side effects like stomach upset or diarrhea reported by some patients. However, since this trial is in an early stage, it primarily aims to assess the treatment's safety in people with PSC. At this stage, researchers first test a treatment in humans, so detailed safety information might still be limited. Prospective participants should discuss potential risks and benefits with a healthcare provider. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for primary sclerosing cholangitis (PSC), which often include medications like ursodeoxycholic acid and immunosuppressants, the oral microbiota-based therapeutic is designed to work by altering the gut microbiome. Researchers are excited about this treatment because it introduces a completely new mechanism of action—using beneficial bacteria to potentially reduce inflammation and improve liver function. This approach could offer a safer alternative with fewer side effects compared to traditional medications, which often have limited effectiveness and can cause significant side effects. The potential for a non-invasive, oral treatment is also a huge plus, making it more convenient for patients.

What evidence suggests that this treatment might be an effective treatment for primary sclerosing cholangitis?

Research has shown that altering the gut microbiota—the community of tiny organisms living in the gut—might offer a promising way to treat primary sclerosing cholangitis (PSC), a liver disease. Studies have found that an oral treatment can help restore a healthy balance of these organisms. In this trial, participants will receive an oral microbiota-based therapeutic to explore its potential in changing the gut's microbial makeup and reducing disease symptoms. Although this specific treatment remains in early testing, similar treatments have shown potential. ^{1 3 4 6 7}

Who Is on the Research Team?

Elizabeth Aby

Principal Investigator

University of Minnesota

Are You a Good Fit for This Trial?

This trial is for individuals with primary sclerosing cholangitis (PSC), a liver condition affecting the bile ducts. Specific eligibility details are not provided, but typically participants would need to meet certain health standards and may be excluded based on factors that could interfere with the study or their safety.

Inclusion Criteria

I have been diagnosed with PSC and have high ALP levels or imaging/biopsy evidence for over 6 months.

My recent scans show no blockage or cancer in my bile ducts.

I am willing and able to follow all study procedures and be available for the entire trial.

Exclusion Criteria

Pregnancy or attempting to become pregnant or breastfeeding

Neutropenia (an absolute neutrophil count < 0.5 x 109 cells/L)

History of allergic reaction to amoxicillin or other beta-lactam antibiotics

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive microbiota transplant therapy (MTT) to evaluate initial safety and feasibility

31 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Oral Microbiota-based Therapeutic

Trial Overview The trial is testing oral vancomycin and oral amoxicillin as part of microbiota transplant therapy (MTT) for PSC. It aims to assess the safety and feasibility of MTT to inform future larger-scale trials targeting this liver condition.

How Is the Trial Designed?

Group I: PCS patients Experimental Treatment 1 Intervention

Who Is Running the Clinical Trial?

University of Minnesota

Lead Sponsor

Trials

1,459

Recruited

1,623,000+

Published Research Related to This Trial

Patients with primary sclerosing cholangitis (PSC) exhibit a distinct microbiome in their bile ducts compared to healthy controls, characterized by reduced biodiversity and an increase in the pathogen Enterococcus faecalis.

The presence of Enterococcus faecalis in the bile ducts is strongly correlated with higher levels of the harmful secondary bile acid taurolithocholic acid, which may contribute to inflammation and cancer risk in PSC patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Alterations of the bile microbiome in primary sclerosing cholangitis. Liwinski, T., Zenouzi, R., John, C., et al.[2020]

A study of 106 participants, including patients with primary sclerosing cholangitis (PSC), ulcerative colitis (UC), and healthy controls, revealed that PSC is associated with specific gut bacteria, such as increased levels of Rothia and Enterococcus, regardless of the presence of inflammatory bowel disease.

Both PSC and UC patients exhibited low bacterial diversity and distinct microbial profiles, indicating that certain gut microbes can differentiate between these conditions and may play a role in their pathogenesis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Distinct gut microbiota profiles in patients with primary sclerosing cholangitis and ulcerative colitis. Bajer, L., Kverka, M., Kostovcik, M., et al.[2018]

Fecal microbiota transplantation (FMT) is safe for patients with primary sclerosing cholangitis (PSC), as no related adverse events were reported in a pilot study involving 10 patients.

FMT led to a significant increase in gut microbiota diversity and was associated with a 30% reduction in alkaline phosphatase (ALP) levels, suggesting a potential therapeutic benefit in managing PSC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fecal Microbiota Transplantation in Patients With Primary Sclerosing Cholangitis: A Pilot Clinical Trial. Allegretti, JR., Kassam, Z., Carrellas, M., et al.[2021]

Germ-free mdr2-/- mice experienced 100% mortality within 8 weeks due to liver disease, but autologous stool transplantation from SPF mice significantly improved survival, highlighting the critical role of gut microbiota in liver health.

Specific bacterial families, such as Lachnospiraceae, were found to be protective against liver fibrosis and inflammation in PSC patients, while others like Enterococcus faecalis were associated with worse clinical outcomes, suggesting potential for targeted microbiome-based therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Protective and aggressive bacterial subsets and metabolites modify hepatobiliary inflammation and fibrosis in a murine model of PSC. Awoniyi, M., Wang, J., Ngo, B., et al.[2023]

This study presents the first successful use of healthy donor fecal transplantation to treat recurrent acute bacterial cholangitis in a patient with primary sclerosing cholangitis, highlighting a novel therapeutic approach.

Following the fecal transplantation, significant improvements were observed in liver biochemistry, bile acid levels, and the bacterial community in the patient's gut, suggesting a positive impact on managing cholangitis symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Healthy Donor Fecal Microbiota Transplantation for Recurrent Bacterial Cholangitis in Primary Sclerosing Cholangitis - A Single Case Report. Philips, CA., Augustine, P., Phadke, N.[2020]

In a study involving 84 patients with primary sclerosing cholangitis (PSC), 51 liver transplanted PSC patients, and 40 healthy controls, researchers found that both PSC and PSC-LT patients had reduced microbial diversity in their gut compared to healthy individuals.

The presence of certain gut bacteria, particularly an increase in Proteobacteria and the pathobiont Klebsiella, was linked to worse liver transplant outcomes, suggesting that gut microbiota may play a significant role in the health of patients with PSC, especially after liver transplantation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A shared mucosal gut microbiota signature in primary sclerosing cholangitis before and after liver transplantation. Hole, MJ., Jørgensen, KK., Holm, K., et al.[2023]

Fecal microbiota transplant (FMT) was found to be safe for noncirrhotic patients with primary sclerosing cholangitis (PSC) who also had inflammatory bowel disease, indicating potential for further exploration as a treatment option.

After FMT, patients experienced an early increase in microbial diversity, although the effects on alkaline phosphatase levels were mixed and there was no significant change in fecal bile acid profiles, suggesting that more research is needed to determine the therapeutic benefits of FMT in PSC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Manipulation of the Gut-Liver Axis Using Microbiome Restoration Therapy in Primary Sclerosing Cholangitis. Bajaj, JS., Hays, RA.[2020]

In a study of 44 patients, including 20 with primary sclerosing cholangitis (PSC), researchers found that the overall microbiome profile was similar across different gut locations, regardless of disease status.

However, patients with PSC showed significant enrichment of specific bacteria, particularly in the Barnesiellaceae family and the Blautia genus, indicating potential microbiome alterations associated with the disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The features of mucosa-associated microbiota in primary sclerosing cholangitis. Torres, J., Bao, X., Goel, A., et al.[2022]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06197308

Evaluation of an Oral Microbiota-based Therapeutic as a ... This pilot clinical trial will evaluate the initial safety and feasibility of microbiota transplant therapy (MTT) inpatients with primary sclerosing cholangitis ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10092549/

Systematic review: microbial manipulation as therapy for ... Emerging data demonstrate that manipulation of the gut microbiota holds promise as an effective therapeutic strategy in PSC. Oral antibiotic ...

3. studyfinder.umn.edu studyfinder.umn.edu/studies/31896

Evaluation of an oral microbiota-based therapeutic as a ... The purpose of this study is to evaluate whether MTT from a healthy donor is safe and can be used to restore the healthy composition of microbiota to help ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S2352345X23002187

Review Microbial Players in Primary Sclerosing Cholangitis This review provides an overview of the current knowledge on the gut bacterial and fungal microbiota in primary sclerosing cholangitis.

5. journals.lww.com journals.lww.com/ajg/Fulltext/2020/06000/Targeting_the_Gut_Microbiome_as_a_Treatment_for.9.aspx?generateEpub=Article%7Cajg:2020:06000:00009%7C10.14309/ajg.0000000000000604%7C

Targeting the Gut Microbiome as a Treatment for Primary ... Targeting the Gut Microbiome as a Treatment for Primary Sclerosing Cholangitis ... (79) found that oral vancomycin was effective for the induction and ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11719443/

Effectiveness and safety of oral vancomycin for the ... Safety outcomes included the following: risk of infection, acute cholangitis, development of cirrhosis, liver decompensation (ascites, ...

7. gastrojournal.org gastrojournal.org/issue/S0016-5085(25)X6002-9?pageStart=81

May-May 2025 Mo1616: LONG-TERM EFFICACY AND SAFETY OF OPEN-LABEL SELADELPAR TREATMENTS IN PATIENTS WITH PRIMARY BILIARY CHOLANGITIS: POOLED INTERIM RESULTS FOR UP TO 3 YEARS ...