Vancomycin for Primary Sclerosing Cholangitis

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

102 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing if vancomycin, an antibiotic, is safe and effective for adults with primary sclerosing cholangitis (PSC). There are reports of vancomycin improving liver health in patients with PSC. The study will measure if vancomycin can improve liver health. Researchers will also look at changes in gut health and inflammation to see how they relate to liver health.

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.

What data supports the effectiveness of the drug vancomycin for primary sclerosing cholangitis?

Research suggests that vancomycin, an antibiotic, may help improve liver function in primary sclerosing cholangitis (PSC) by reducing markers of liver damage and improving symptoms. In a study, patients treated with vancomycin showed significant improvements in liver enzyme levels and overall health, indicating its potential as a promising treatment for PSC. ^{1 2 3 4 5}

Is oral vancomycin safe for humans?

Oral vancomycin has been used in studies for primary sclerosing cholangitis, and while it shows promise, about 8.9% of patients experienced side effects severe enough to stop treatment. This suggests that while generally safe, there can be significant adverse effects for some individuals. ^{1 2 4 5 6}

How is the drug vancomycin unique for treating primary sclerosing cholangitis?

Vancomycin is unique for treating primary sclerosing cholangitis (PSC) because it is an antibiotic that may help by altering the gut microbiome and acting as an immunomodulator, which is different from other treatments that do not target these mechanisms. It has shown promise in improving liver function and reducing disease markers in PSC, a condition with no standard effective therapy. ^{1 2 4 5 7}

Research Team

Elizabeth Carey, MD

Principal Investigator

Mayo Clinic

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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 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]

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 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]

References

1. Romania 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. [2022]

2. Korea (South) pubmed.ncbi.nlm.nih.gov

Oral Vancomycin Therapy in a Child with Primary Sclerosing Cholangitis and Severe Ulcerative Colitis. [2020]

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

Randomised clinical trial: vancomycin or metronidazole in patients with primary sclerosing cholangitis - a pilot study. [2022]

4. United States 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. [2023]

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

Open-label prospective therapeutic clinical trials: oral vancomycin in children and adults with primary sclerosing cholangitis. [2021]

6. Japan 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. [2022]

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

Oral Vancomycin, Ursodeoxycholic Acid, or No Therapy for Pediatric Primary Sclerosing Cholangitis: A Matched Analysis. [2023]