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

Trial Summary

What is the purpose of this trial?

This pilot clinical trial will evaluate the initial safety and feasibility of microbiota transplant therapy (MTT) inpatients with primary sclerosing cholangitis (PSC). This trial will inform development of future trials in treatment of PSC.

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.

What data supports the effectiveness of the treatment Oral Microbiota-based Therapeutic for Sclerosing Cholangitis?

A case report showed that transplanting healthy donor fecal microbiota (the community of bacteria in the gut) helped improve liver function and reduce recurrent bacterial infections in a patient with primary sclerosing cholangitis, suggesting potential benefits of microbiota-based treatments. ^{1 2 3 4 5}

Is Microbiota Transplant Therapy safe for humans?

A study found that fecal microbiota transplant (FMT) was safe for patients with primary sclerosing cholangitis (PSC) and inflammatory bowel disease in remission, showing stable microbial diversity and donor engraftment without significant adverse effects. ^{1 3 4 6 7}

How is Microbiota Transplant Therapy different from other treatments for sclerosing cholangitis?

Microbiota Transplant Therapy is unique because it involves transferring healthy bacteria from a donor to the patient's gut, aiming to restore the balance of gut bacteria and improve liver health. Unlike traditional treatments, this approach targets the gut-liver connection and has shown potential in altering liver biochemistry and microbial diversity, offering a novel way to manage sclerosing cholangitis, which currently lacks effective medical therapies. ^{1 2 4 6 8}

Research Team

Elizabeth Aby

Principal Investigator

University of Minnesota

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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 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 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]

References

1. England pubmed.ncbi.nlm.nih.gov

Protective and aggressive bacterial subsets and metabolites modify hepatobiliary inflammation and fibrosis in a murine model of PSC. [2023]

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

Healthy Donor Fecal Microbiota Transplantation for Recurrent Bacterial Cholangitis in Primary Sclerosing Cholangitis - A Single Case Report. [2020]

3. England pubmed.ncbi.nlm.nih.gov

Alterations of the bile microbiome in primary sclerosing cholangitis. [2020]

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

Distinct gut microbiota profiles in patients with primary sclerosing cholangitis and ulcerative colitis. [2018]

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

The features of mucosa-associated microbiota in primary sclerosing cholangitis. [2022]

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

Manipulation of the Gut-Liver Axis Using Microbiome Restoration Therapy in Primary Sclerosing Cholangitis. [2020]

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

A shared mucosal gut microbiota signature in primary sclerosing cholangitis before and after liver transplantation. [2023]

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

Fecal Microbiota Transplantation in Patients With Primary Sclerosing Cholangitis: A Pilot Clinical Trial. [2021]