Vancomycin for Primary Sclerosing Cholangitis

Age: < 65

Sex: Any

Trial Phase: Phase 1

Sponsor: Sacramento Pediatric Gastroenterology

Must not be taking: Antibiotics, Immunomodulators

Disqualifiers: Pregnancy, others

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

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 3 months

200 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study is twofold. First, is to determine whether vancomycin is effective in the early treatment of Biliary Atresia (BA) and Primary Sclerosing Cholangitis (PSC), and if so, by what mechanism. Secondly, to characterize human intestinal microbial communities and their interactions with the host.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you have taken antibiotics or immunomodulators (drugs that modify the immune system) in the last 3 months.

What data supports the effectiveness of the drug Vancomycin for treating Primary Sclerosing Cholangitis?

Some studies suggest that oral vancomycin may help improve liver function and symptoms in patients with primary sclerosing cholangitis (PSC). For example, a case report showed a 15-year-old with PSC and ulcerative colitis experienced normalization of liver enzymes and symptom resolution after vancomycin treatment, indicating potential benefits that need further research. ^{1 2 3 4 5}

Is vancomycin safe for use in humans?

Vancomycin has been used in studies for primary sclerosing cholangitis and other conditions, with some patients experiencing side effects. In one review, 8.9% of patients had side effects severe enough to stop treatment, indicating that while generally safe, it can cause significant adverse effects in some individuals. ^{1 4 5 6 7}

How does the drug vancomycin differ from other treatments for primary sclerosing cholangitis?

Vancomycin is unique for primary sclerosing cholangitis because it is an antibiotic that may work by altering the gut microbiome and modulating the immune system, unlike other treatments which are not universally accepted or effective. It is administered orally and has shown promise in improving liver function and symptoms in some patients, but more research is needed to confirm its efficacy. ^{1 2 4 5 8}

Research Team

Yinka Davies, M.D.

Principal Investigator

Sacramento Pediatric Gastroenterology

Eligibility Criteria

This trial is for individuals with primary sclerosing cholangitis or biliary atresia, who are suitable for vancomycin treatment. It's also open to those with chronic intestinal disorders or undergoing endoscopy. People can't join if they've used antibiotics/immunomodulators in the last 3 months or if they're pregnant.

Inclusion Criteria

I have a liver condition that might improve with vancomycin.

I have a liver or intestinal condition, or I'm getting an endoscopy.

Exclusion Criteria

I have not taken antibiotics or immunomodulators in the last 3 months.

I am not pregnant.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive oral vancomycin to assess its effectiveness in treating Primary Sclerosing Cholangitis and Biliary Atresia

3 months

Regular visits for blood tests, imaging studies, and/or liver biopsy

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Vancomycin

Trial Overview The study aims to see if vancomycin effectively treats early-stage Biliary Atresia and Primary Sclerosing Cholangitis, and how it interacts with gut microbes.

Participant Groups

Group I: Oral Vancomycin Experimental Treatment 1 Intervention

Every participant with PSC or BA will received the same Arm of Oral Vancomycin

Vancomycin is already approved in United States, European Union, Canada, Japan for the following indications:

Approved in United States as Vancocin for:

• Severe infections caused by susceptible strains of methicillin-resistant staphylococci
• Enterocolitis caused by Staphylococcus aureus
• Staphylococcal endocarditis

Approved in European Union as Vancomycin for:

• Severe infections caused by Gram-positive bacteria
• Endocarditis
• Peritonitis associated with continuous ambulatory peritoneal dialysis (CAPD)

Approved in Canada as Vancomycin for:

• Severe infections caused by susceptible strains of methicillin-resistant staphylococci
• Enterocolitis caused by Staphylococcus aureus

Approved in Japan as Vancomycin for:

• Severe infections caused by Gram-positive bacteria
• Endocarditis

Who Is Running the Clinical Trial?

Sacramento Pediatric Gastroenterology

Lead Sponsor

Trials

1

Recruited

200+

Findings from Research

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]

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]

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 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]

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]

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]

A case study reports that oral vancomycin successfully normalized liver biochemistry in an adult patient with recurrent primary sclerosing cholangitis (PSC) four years after liver transplantation, suggesting a potential new treatment option.

This case adds to existing evidence that vancomycin may have immunomodulatory and anti-inflammatory effects beneficial for PSC, a disease with limited treatment options beyond liver transplantation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of oral vancomycin in recurrent primary sclerosing cholangitis following liver transplantation. Hey, P., Lokan, J., Johnson, P., et al.[2018]

References

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

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

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

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

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

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

4. 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]

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

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

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

Effects of Antibiotic Therapy in Primary Sclerosing Cholangitis with and without Inflammatory Bowel Disease: A Systematic Review and Meta-Analysis. [2023]

8. England pubmed.ncbi.nlm.nih.gov

Efficacy of oral vancomycin in recurrent primary sclerosing cholangitis following liver transplantation. [2018]