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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether vancomycin, an antibiotic, can help treat Primary Sclerosing Cholangitis (PSC) and Biliary Atresia (BA), both of which affect the bile ducts and liver. Researchers aim to understand how vancomycin works and learn more about gut bacteria and their interactions with the body. Participants will take vancomycin orally. The trial suits individuals with PSC or BA who haven't used antibiotics in the past three months. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants a chance to contribute to groundbreaking research.

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.

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

Research has shown that oral vancomycin is generally safe for individuals with conditions like primary sclerosing cholangitis (PSC). Studies have found that it typically causes mild side effects, meaning most people tolerate it well. For instance, nearly half of the patients with PSC and inflammatory bowel disease (IBD) experienced improvement without major side effects.

Additionally, small studies and case reports suggest that oral vancomycin may help improve PSC symptoms. While these studies provide some insights, treatments in early trial phases are still being tested for safety and effectiveness. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for PSC?

Vancomycin is unique because it offers a different approach to treating Primary Sclerosing Cholangitis (PSC) compared to the usual therapies like ursodeoxycholic acid or liver transplantation. Unlike other treatments, vancomycin is an antibiotic that may work by modifying the gut microbiome, potentially reducing inflammation and liver damage associated with PSC. Researchers are excited about vancomycin because of its potential to target the underlying causes of the disease directly, offering hope for improved outcomes in a condition that currently lacks effective medical treatments.

What evidence suggests that vancomycin might be an effective treatment for Primary Sclerosing Cholangitis?

Research has shown that oral vancomycin might help treat Primary Sclerosing Cholangitis (PSC). In one study, 80% of PSC patients experienced symptom relief after four weeks of treatment, and all participants showed signs of healing in the gut lining. Another study found that oral vancomycin improved liver function in patients waiting for liver transplants. Additionally, almost half of PSC patients who also had inflammatory bowel disease (IBD) felt better after taking oral vancomycin. These findings suggest that oral vancomycin could benefit people with PSC. Participants in this trial will receive oral vancomycin to further evaluate its effectiveness for PSC. ^{2 6 7 8 9}

Who Is on the Research Team?

Yinka Davies, M.D.

Principal Investigator

Sacramento Pediatric Gastroenterology

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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 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 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]

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]

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]

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 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]

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 ... Our data demonstrated that after 4 weeks, 80% of patients attained clinical remission, and 100% showed mucosal healing. A significant reduction ...

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 ... Oral vancomycin has shown promising results by improving liver biochemistry in patients with pre-transplant PSC, and, pending further studies, may offer a ...

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

Effectiveness and safety of oral vancomycin for the ... OVT was associated with clinical response/remission in almost half of patients with IBD-PSC with a favorable side effect profile.

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 was rapidly effective and safe, with 55% of non-PSC PIBD patients achieving/maintaining remission and 48% able to reduce/stop ...

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

Effect and Safety of Oral Vancomycin in Primary Sclerosing ... Effect and Safety of Oral Vancomycin in Primary Sclerosing Cholangitis Patients ; ClinicalTrials.gov ID NCT02605213 ; Sponsor Tehran University of ...

9. journals.lww.com journals.lww.com/10.14309/01.ajg.0000787072.84958.2f

S3385 Effect of Vancomycin on Primary Sclerosing... There appears to be a microbiome association with PSC, and very small studies and case reports suggest a beneficial effect of oral vancomycin on PSC outcomes.