Vancomycin for Primary Sclerosing Cholangitis

No longer recruiting at 3 trial locations

Overseen By Latasha Bunkley

Age: 18+

Sex: Any

Trial Phase: Phase 2 & 3

Sponsor: Elizabeth Carey

Must be taking: UDCA, prednisone, methotrexate, others

Must not be taking: Antibiotics

Disqualifiers: Pregnancy, Hepatitis B, Hepatitis C, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 18 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if vancomycin is safe and effective for treating primary sclerosing cholangitis (PSC), a liver disease that inflames and scars bile ducts. Participants will receive either vancomycin or a placebo (a treatment with no active medicine) to compare results. The trial is ideal for individuals diagnosed with PSC who have elevated liver enzyme levels and no other liver diseases or conditions. Participants should not have used antibiotics recently and must be willing to follow the study guidelines. As a Phase 2, Phase 3 trial, this research measures the treatment's effectiveness in an initial, smaller group and represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

Will I have to stop taking my current medications?

If you are taking medications like UDCA, azathioprine, prednisone, methotrexate, a 5-aminosalicylic acid, biologic therapy, or probiotics, you should continue them at the same dose during the trial. If you have been on obeticholic acid or other experimental therapies for PSC, you need to stop them for 3 months before joining the study.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that taking oral vancomycin can lead to better health outcomes for people with primary sclerosing cholangitis (PSC). Some studies have found that vancomycin is generally safe. For example, one study found that many patients experienced improved lab test results after treatment, known as biochemical remission. Another study reported no major side effects in a small group of participants.

These findings suggest that vancomycin is usually well-tolerated by people with PSC. However, side effects can vary among individuals. Prospective trial participants should discuss any concerns with a healthcare provider. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for primary sclerosing cholangitis?

Unlike the standard treatments for primary sclerosing cholangitis, which often focus on managing symptoms and complications, vancomycin offers a different approach by potentially addressing the underlying inflammation and bile duct damage. Vancomycin is an antibiotic that may modulate the gut microbiome, which researchers believe plays a role in the disease's progression. This unique mechanism of action sets it apart from current therapies like ursodeoxycholic acid, which mainly aim to improve liver function tests without altering disease progression. Researchers are excited about vancomycin because it offers hope for not just managing symptoms but potentially altering the course of the disease.

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

Research has shown that oral vancomycin, which participants in this trial may receive, might help treat primary sclerosing cholangitis (PSC). In one study, 12 out of 15 patients experienced significant symptom improvement. Another report found that patients showed better symptoms and lab results after taking vancomycin. Additionally, vancomycin has successfully treated recurrent PSC in a patient after a liver transplant. These findings suggest that vancomycin could help reduce symptoms and improve liver function in people with PSC. ^{1 6 7 8 9}

Who Is on the Research Team?

Elizabeth Carey, MD

Principal Investigator

Mayo Clinic

Are You a Good Fit for This Trial?

Adults aged 18-76 with Primary Sclerosing Cholangitis (PSC) can join this trial. They must have certain liver test results and imaging that confirms PSC without other liver diseases or complications like cancer. Stable doses of specific medications are allowed, but no antibiotics in the last 3 months or recent experimental therapies for PSC without a washout period.

Inclusion Criteria

My recent ultrasound showed no signs of blocked bile ducts or cancer.

I am taking certain medications or supplements and can keep the dose the same during treatment.

I have not taken obeticholic acid or other experimental treatments for PSC in the last 3 months.

Exclusion Criteria

I have taken antibiotics within the last 3 months.

I have PSC and may also have autoimmune hepatitis or primary biliary cholangitis.

I have been diagnosed with secondary sclerosing cholangitis.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive oral vancomycin or placebo for primary sclerosing cholangitis, with assessments at 6, 12, and 18 months

18 months

Follow-up

Participants are monitored for safety and effectiveness after treatment, with assessments at 3 and 6 months post-treatment

6 months

What Are the Treatments Tested in This Trial?

Interventions

• Placebo
• Vancomycin

Trial Overview The trial is testing if vancomycin is safe and effective for treating PSC compared to a placebo. Participants will be randomly assigned to receive either vancomycin or an inactive substance, with neither the participants nor the researchers knowing who receives which treatment until after the study ends.

How Is the Trial Designed?

Group I: Vancomycin Experimental Treatment 1 Intervention

Group II: Placebo Placebo Group 1 Intervention

Who Is Running the Clinical Trial?

Elizabeth Carey

Lead Sponsor

Trials

2

Recruited

120+

Arizona State University

Collaborator

Trials

311

Recruited

109,000+

Published Research Related to This Trial

A 15-year-old girl with primary sclerosing cholangitis (PSC) and ulcerative colitis showed significant improvement after treatment with oral vancomycin, including normalization of liver enzymes and resolution of UC symptoms.

The study suggests that vancomycin may work by changing the gut microbiome and modulating the immune response, indicating its potential as a new treatment for PSC that warrants further investigation in clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oral Vancomycin Therapy in a Child with Primary Sclerosing Cholangitis and Severe Ulcerative Colitis. Buness, C., Lindor, KD., Miloh, T.[2020]

A 23-year-old female patient with small-duct primary sclerosing cholangitis (PSC) and ulcerative colitis showed significant improvement after 8 years of treatment with oral vancomycin, including normalization of liver enzymes and resolution of UC symptoms.

The effectiveness of oral vancomycin appeared to depend on the specific brand and dosage, suggesting that variations in drug formulation may influence treatment outcomes and warrant further investigation in clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Successful response of primary sclerosing cholangitis and associated ulcerative colitis to oral vancomycin may depend on brand and personalized dose: report in an adolescent. Buness, CW., Johnson, KM., Ali, AH., et al.[2022]

In a randomized, placebo-controlled trial involving 29 patients with primary sclerosing cholangitis (PSC), oral vancomycin significantly reduced the PSC Mayo risk score and alkaline phosphatase levels after 12 weeks of treatment, indicating its potential efficacy.

Patients receiving vancomycin also experienced significant improvements in secondary outcomes, including reduced inflammation markers and symptoms like fatigue and pruritus, suggesting that vancomycin may be a beneficial treatment option for PSC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Triple Blinded, Randomized, Placebo-Controlled Clinical Trial to Evaluate the Efficacy and Safety of Oral Vancomycin in Primary Sclerosing Cholangitis: a Pilot Study. Rahimpour, S., Nasiri-Toosi, M., Khalili, H., et al.[2022]

In a study involving 59 patients with primary sclerosing cholangitis (PSC), oral vancomycin (OV) treatment for a median duration of 2.7 years led to significant reductions in liver enzymes, with 96% of patients showing decreased gamma glutamyl transferase (GGT), 81.3% for alkaline phosphatase (ALP), and 94.9% for alanine aminotransferase (ALT).

OV was well-tolerated with no treatment-related adverse events reported, suggesting it is a safe option for managing PSC, and the results indicate a need for further randomized controlled trials to confirm its efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Open-label prospective therapeutic clinical trials: oral vancomycin in children and adults with primary sclerosing cholangitis. Ali, AH., Damman, J., Shah, SB., et al.[2021]

Antibiotic therapy in primary sclerosing cholangitis (PSC) significantly reduced key health markers, including serum alkaline phosphatase (ALP), Mayo PSC Risk Score (MRS), and total serum bilirubin (TSB) by 33.2%, 36.1%, and 28.8%, respectively, based on a systematic review of 5 studies involving 124 patients.

Vancomycin was particularly effective, showing a 65.6% reduction in ALP, while adverse events leading to discontinuation of therapy occurred in 8.9% of patients, indicating that while antibiotics can improve PSC symptoms, they may also cause side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of Antibiotic Therapy in Primary Sclerosing Cholangitis with and without Inflammatory Bowel Disease: A Systematic Review and Meta-Analysis. Shah, A., Crawford, D., Burger, D., et al.[2023]

In a study of 35 patients with primary sclerosing cholangitis (PSC), oral vancomycin significantly reduced alkaline phosphatase levels, achieving the primary endpoint with a 43% decrease in the low-dose group and a 40% decrease in the high-dose group.

Both vancomycin and metronidazole showed efficacy in treating PSC, but vancomycin had fewer adverse effects, making it a potentially safer option for patients compared to metronidazole.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomised clinical trial: vancomycin or metronidazole in patients with primary sclerosing cholangitis - a pilot study. Tabibian, JH., Weeding, E., Jorgensen, RA., et al.[2022]

In a study of 264 children with primary sclerosing cholangitis (PSC), treatment with oral vancomycin or ursodeoxycholic acid did not show any significant improvement in liver function or disease progression compared to observation alone after one year.

The findings suggest that many children with mild PSC may experience spontaneous normalization of liver biochemistry without treatment, highlighting the need for placebo-controlled trials to identify effective therapies for pediatric PSC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oral Vancomycin, Ursodeoxycholic Acid, or No Therapy for Pediatric Primary Sclerosing Cholangitis: A Matched Analysis. Deneau, MR., Mack, C., Mogul, D., et al.[2023]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39495039/

The Effectiveness of Oral Vancomycin on Inflammatory ... Conclusions: Oral vancomycin appears safe and effective to treat IBD in a subset of PSC patients. Future studies would benefit from prospective ...

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

Effectiveness and safety of oral vancomycin for the ... Primary IBD clinical and objective effectiveness outcomes. Clinical response was noted in 47.6% (138/290) of IBD-PSC patients treated with OVT.

3. academic.oup.com academic.oup.com/ecco-jcc/article/19/2/jjae189/7923930

Open Label Vancomycin in Primary Sclerosing Cholangitis ... Oral vancomycin resulted in clinical remission in 12/15 patients and significant reductions in fecal calprotectin. Oral vancomycin was ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT05876182

Vancomycin in Primary Sclerosing Cholangitis in Italy The use of oral vancomycin (OV), a glycopeptide antibiotic has been reported to be associated with improvement in clinical symptoms and laboratory abnormalities ...

5. casereports.bmj.com casereports.bmj.com/content/2017/bcr-2017-221165

Efficacy of oral vancomycin in recurrent primary sclerosing ... This report is the first to describe the successful treatment of recurrent PSC post-transplantation with vancomycin in an adult patient.

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39802627/

Effectiveness and safety of oral vancomycin for the ... The biochemical remission rate post-OVT was 68.8% (55/80) and endoscopic remission was 39.4% (80/203). Three studies (n = 11) reported no ...

7. academic.oup.com academic.oup.com/ecco-jcc/article/19/Supplement_1/i1902/7971937

P1031 Effectiveness and safety of oral vancomycin in the ... Oral vancomycin is associated with improved inflammatory bowel disease clinical outcomes in primary sclerosing cholangitis-associated ...

8. clinicaltrials.gov clinicaltrials.gov/study/NCT02605213

Effect and Safety of Oral Vancomycin in Primary Sclerosing ... Primary sclerotic cholangitis (PSC) is an inflammatory process of sclerotic cholangitis that involves intra and extra hepatic biliary system.

9. onlinelibrary.wiley.com onlinelibrary.wiley.com/doi/abs/10.1002/jpn3.70180

Effectiveness and safety of oral vancomycin in non‐primary ... Oral vancomycin is associated with improved inflammatory bowel disease clinical outcomes in primary sclerosing cholangitis-associated ...