RecruitingNCT05876182VanC-ITUpdated Jul 25, 2025

Vancomycin in Primary Sclerosing Cholangitis in Italy

A Phase 2 interventional study of Oral Vancomycin and Placebo in Primary Sclerosing Cholangitis, Liver and Intrahepatic Bile Duct Disorder and IBD, sponsored by University of Milano Bicocca. Recruiting at 1 site in Italy. Open to participants aged 15 Years to 70 Years. Per ClinicalTrials.gov, last updated 2025-07-25.

Sponsored by University of Milano Bicocca · Phase 2, Interventional, and Treatment

From the registry’s dates

Primary completion was expected by Jun 2026, 4 months ago, but the record still lists the study as recruiting.
Started Jun 2023; still recruiting 3 years 3 months later.

Phase: Phase 2
Study type: Interventional
Enrollment: 84
Allocation: Randomized
Ages: 15 Years to 70 Years
Sex: All

Study summary

Primary sclerosing cholangitis (PSC) is chronic fibroinflammatory disease of the liver. There is still no medical therapy proven to halt the progression of PSC or prevent its serious complications.

Read the detailed description

Primary sclerosing cholangitis (PSC) is chronic fibroinflammatory disease of the liver characterized by chronic inflammation and sclerosis of the intrahepatic and/or extrahepatic bile ducts, and a risk for progression to liver failure and development of colorectal and hepatobiliary cancer. Both children and adults are affected. Patients with PSC have a diminished life expectancy with a median survival of 17 years after diagnosis. Despite the high mortality associated with PSC and the efforts to optimize its management, there is no medical therapy proven to halt the progression of PSC or prevent its serious complications. There is a strong yet poorly understood relationship between PSC and inflammatory bowel disease (IBD); nearly 70%-80% of PSC patients have IBD, mainly ulcerative colitis (UC). Increasing evidence is pointing out the role of gut microbiota in the pathogenesis of PSC. The 'leaky gut' theory implies that either bacteria or their toxic metabolites translocate from the inflamed intestinal mucosa into the portal circulation and into the liver causing liver and biliary injury. The gut microbiota of PSC patients, compared to IBD patients and healthy controls, showed decreased microbial diversity, and over-represented intestinal pathobionts (i.e., organisms which, under normal circumstances, lives as a non-harming symbiont). Several antibiotics, including vancomycin and metronidazole, have been investigated in PSC. The use of oral vancomycin (OV), a glycopeptide antibiotic has been reported to be associated with improvement in clinical symptoms and laboratory abnormalities in patients with PSC; however, prospective studies in adult and young adult patients in Europe are lacking.

Our scientific community therefore seeks to examine the safety and efficacy of OV in patients with PSC in a randomized placebo-controlled clinical trial.

This is a Phase 2 randomized, double bind, placebo-controlled, monocentric study evaluating the safety and efficacy of two doses of oral vancomycin (i.e. 750 mg and 1500 mg/day) in subject between 15 - 70 years old with PSC with or without IBD. The study will consist of 10-week screening period (including a run-in phase), 24 weeks of treatment, and follow-up visits at 4 and 12 weeks after completion of treatment to evaluate what happens after treatment stop. Subjects will be randomized to placebo or treatment and stratifying by baseline presence of fibrosis by fibroscan value at baseline (\< or ≥14.4 kPa corresponding to F4 fibrosis), as this parameter could affect the likelihood of reaching the primary composite outcome measure.

The knowledge gained from our proposed clinical trial will help us determine if OV should be considered as a treatment option in patients with PSC. Furthermore, the use of state-of-the art technology applied in this study will shed light on the relationship between the gut microbiome, bile acids, immune-mediators, including cytokines, and PSC.

Conditions studied

Primary Sclerosing Cholangitis
Liver and Intrahepatic Bile Duct Disorder
IBD

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Keywords

liver
oral vancomycin
primary sclerosing cholangitis
Inflammatory bowel disease

In context

Cholangitis, Sclerosing

149 studies on the registry are indexed under Cholangitis, Sclerosing; 37 are open to participants now.

This study's planned enrollment of 84 is above the median of 34 across 96 interventional studies indexed under Cholangitis, Sclerosing.

Browse Cholangitis, Sclerosing studies →

Lead sponsor

University of Milano Bicocca is the lead sponsor of 124 studies on the registry; 48 are open to participants now.

Counted across the registry records on this site, refreshed daily.

Who can participate

Ages eligible: 15 Years to 70 Years
Sexes eligible: All
Accepts healthy volunteers: No

Inclusion criteria

Willing and able to give informed consent prior to any study specific procedure being performed;
Male and non-pregnant, non-lactating female subjects, including women of child bearing potential (WOCBP), between 15-70 years of age at the time of informed consent;
Diagnosis of large-duct PSC based on cholangiogram (at MRCP, ERCP, PTC) according to the most recent published guidelines (EASL);
Baseline ALP ≥1.5 times upper limit normal at screening;
Absence of biliary obstruction and/or malignancy within 6-12 months of entry into the study;
If a patient is on ursodeoxycholic acid (UDCA) or 5-aminosalicylic acid he or she is expected to remain on the same daily dose during the study period;
Patients who received antibiotics or probiotics may participate if they had a washout period of at least 3-month prior to study entry;
If a patient has been on obeticholic acid or other experimental therapies (e.g. cilofexor and norUDCA) for PSC, they must complete a 3-month washout period before study entry;
PSC with or without IBD. IBD diagnosis should be documented and with a minimum disease duration of 6 months, as determined by endoscopic and histopathology assessment. IBD should be in clinical remission or mildly active according to CDAI and partial Mayo score for CD and UC, respectively (i.e. patients with CDAI score \< 220 and pMayo score \<5). Patients without documented IBD need a colonoscopy with segmental biopsies within 12 months prior to baseline visit;
Female subjects of childbearing potential must test negative for pregnancy at screening, baseline and follow-up visits and if engage in sexual intercourse must agree to use specific methods of contraception.
Male subjects with female partners of childbearing potential must use condoms during treatment and until the end of relevant systemic exposure.

Exclusion criteria

Exclusion Criteria:

Receiving an antibiotic or probiotic within 3 months prior to the study;
Expected to receive antibiotics within the weeks leading up to enrollment (such as patients with recurrent cholangitis, ongoing infectious illnesses, etc.);
Allergy to vancomycin or teicoplanin;
Biliary intervention within 3 months prior to study enrollment or planned;
Alcohol abuse (defined as greater than 14 standard drinks units per week in men; greater than 7 standard drinks units per week);
Pregnancy and lactation;
Advanced renal disease (GFR\< 70);
Active hepatitis B and/or C infection;
Other chronic or cholestatic liver diseases such as PBC, autoimmune hepatitis, nonalcoholic steatohepatitis, alcoholic liver disease, Wilson's disease, hemochromatosis, α-1 antitrypsin deficiency, IgG4-related sclerosing cholangitis, and liver cancer;
History of CCA;
Advanced liver disease (history of variceal bleeding, ascites, hepatic encephalopathy, and/or bilirubine >4 mg/dL);
On active transplantation list;
IBD with uncontrolled moderate to severe activity;
Active treatment or within the previous four weeks (washout period) with any immunosuppressive medication for controlling IBD (i.e. azathioprine, 6-mercaptopurine, tacrolimus, methotrexate, infliximab, adalimumab, golimumab, vedolizumab, ustekinumab, tofacitinib, ozanimod). Treatment with corticosteroids (including budesonide, budesonide MMX and beclomethasone) in the previous four weeks
Active treatment with rifampicin or within the previous three months (washout period);
Dose change within last 3 months prior to baseline of concomitant treatment with vitamin D or fibrates;
Treatment with any experimental drug within the previous three months;
Any known relevant infectious disease (e.g. active tuberculosis, AIDS defining disease);
History or active hearing problems;
Any active malignant disease;
Well found doubt about patient's cooperation, e.g. addiction to alcohol or drugs;
Imprisoned person, person admitted to nursing homes, persons under legal guardianship, and persons not able to express their consent.

Study design

Phase: Phase 2
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel assignment
Masking: Double (Participant, Investigator)
Enrollment: 84 participants (estimated)

Study arms

Experimental
Oral Vancomycin 750
28 subjects with PSC will be randomized to this arm. They will take 2 tablet (1 of vancomycin 250 mg and 1 of placebo), three times a day administered orally (total dose 750 mg/daily).
Drug: Oral Vancomycin
Experimental
Oral Vancomycin 1500
28 subjects with PSC will be randomized to this arm.They will take 2 tablet of 250 mg of vancomycin three times a day administered orally (total dose 1500mg/daily)
Drug: Oral Vancomycin
Placebo comparator
Placebo
28 subjects with PSC will be randomized to this arm. They will take 2 tablet (placebo-to-match oral vancomycin) administered orally three times a day.
Other: Placebo

Interventions

DrugOral Vancomycin
The investigator will identify potential participants and confirm the diagnosis of PSC. Subjects will be screened within 10 weeks before randomization to determine the eligibility. Study participants will be consecutively randomized to oral vancomycin or placebo and investigational drug and placebo dispensed.
Also known as: OV
OtherPlacebo
The investigator will identify potential participants and confirm the diagnosis of PSC. Subjects will be screened within 10 weeks before randomization to determine the eligibility. Study participants will be consecutively randomized to oral vancomycin or placebo and investigational drug and placebo dispensed.

What researchers measure

Primary outcomes

Change from baseline in alkaline phosphatase (ALP) levels
ALP levels at 6 months
Time frame: From baseline to 6 months

Secondary outcomes

Safety and tolerability of OV in each treatment arm
Adverse events
Time frame: From baseline to 6 months
Clinical hematology
White blood cells (10\^3/uL)
Time frame: From baseline to 6 months
Clinical hematology
Hemoglobin (g/dl)
Time frame: From baseline to 6 months
Clinical hematology
Hematocrit (%)
Time frame: From baseline to 6 months
Clinical hematology
MCV (Mean Corpuscular Volume) (fL)
Time frame: From baseline to 6 months
Clinical hematology
Platelets (10\^3/uL)
Time frame: From baseline to 6 months
Clinical hematology
Absolute neutrophils (10\^3/uL)
Time frame: From baseline to 6 months
Clinical hematology
Absolute lymphocytes (10\^3/uL)
Time frame: From baseline to 6 months
Clinical hematology
PT (Prothrombin Time, Ratio)
Time frame: From baseline to 6 months
Clinical hematology
INR
Time frame: From baseline to 6 months
Clinical chemistry
Total proteins (g/dl)
Time frame: From baseline to 6 months
Clinical chemistry
Albumin (g/dl)
Time frame: From baseline to 6 months
Clinical chemistry
Gamma (g/dl)
Time frame: From baseline to 6 months
Clinical chemistry
Sodium (mmol/l)
Time frame: From baseline to 6 months
Clinical chemistry
Creatinine (mg/dl)
Time frame: From baseline to 6 months
Clinical chemistry
Potassium (mmol/l)
Time frame: From baseline to 6 months
Clinical chemistry
Urea (mg/dl)
Time frame: From baseline to 6 months
Clinical chemistry
Glucose (mg/dl)
Time frame: From baseline to 6 months
Clinical chemistry
Total bilirubin (mg/dl)
Time frame: From baseline to 6 months
Clinical chemistry
Direct bilirubin (mg/dl)
Time frame: From baseline to 6 months
Clinical chemistry
GGT (U/l)
Time frame: From baseline to 6 months
Clinical chemistry
AST (U/l)
Time frame: From baseline to 6 months
Clinical chemistry
ALT (U/l)
Time frame: From baseline to 6 months
Clinical chemistry
Triglycerides (mg/dl)
Time frame: From baseline to 6 months
Clinical chemistry
Cholesterol (Total) (mg/dl)
Time frame: From baseline to 6 months
Clinical chemistry
High Density Lipoprotein (HDL Cholesterol) (mg/dl)
Time frame: From baseline to 6 months
Clinical chemistry
PCR (C Reactive Protein) (mg/dl)
Time frame: From baseline to 6 months
Clinical chemistry
IgG (mg/dl)
Time frame: From baseline to 6 months
Clinical chemistry
IgA (mg/dl)
Time frame: From baseline to 6 months
Clinical chemistry
IgM (mg/dl)
Time frame: From baseline to 6 months
Clinical chemistry
Ferritin (ng/ml)
Time frame: From baseline to 6 months
Single 12-lead electrocardiograms
Sinus rhythm
Time frame: From baseline to 6 months
Single 12-lead electrocardiograms
QTc (msec)
Time frame: From baseline to 6 months
Urine analysis
pH
Time frame: From baseline to 6 months
Urine analysis
Specific gravity
Time frame: From baseline to 6 months
Urine analysis
Hemoglobin
Time frame: From baseline to 6 months
Urine analysis
ACR (mg/g)
Time frame: From baseline to 6 months
Urine analysis
PCR (mg/g)
Time frame: From baseline to 6 months
Vital sign measurements
Body weight (kg)
Time frame: From baseline to 6 months
Vital sign measurements
Systolic blood pressure (mmHg)
Time frame: From baseline to 6 months
Vital sign measurements
Diastolic blood pressure (mmHg)
Time frame: From baseline to 6 months
Vital sign measurements
Heart Rate (bpm)
Time frame: From baseline to 6 months
Vital sign measurements
Temperature (°C)
Time frame: From baseline to 6 months
Changes in the PSC score
Revised Mayo Risk Score (Calculation formula = 0.03 (age \[y\]) + 0.54 loge (bilirubin \[mg/dL\]) + 0.54 loge (aspartate aminotransferase \[U/L\]) + 1.24 (variceal bleeding \[0/1\]) - 0.84 (albumin \[g/dL\]) (Higher scores indicate greater disease severity)
Time frame: From baseline to 6 months
Changes in the IBD score
Clinical Mayo Score (Partial Mayo Score) -(0-1=Remission; 2-4 = Mild activity; 5-7 = Moderate activity; 7-9 = Severe activity)
Time frame: From baseline to 6 months
Liver stiffness measurements
Stiffness (kPa/s)
Time frame: From baseline to 6 months
Liver stiffness measurements
Stiffness IQR/median (%)
Time frame: From baseline to 6 months
Liver stiffness measurements
CAP (dB/m)
Time frame: From baseline to 6 months
Liver stiffness measurements
CAP IQR/median (%)
Time frame: From baseline to 6 months
MRCP (Magnetic Resonance Cholangiopancreatography)
Disease localisation
Time frame: From baseline to 6 months
MRCP (Magnetic Resonance Cholangiopancreatography)
Presence of dominant stenosis
Time frame: From baseline to 6 months
MRCP (Magnetic Resonance Cholangiopancreatography)
Radiological signs of cirrhosis
Time frame: From baseline to 6 months
Cytokines changes
TGF-β levels
Time frame: From baseline to 6 months
Cytokines changes
IL-4 levels
Time frame: From baseline to 6 months
Cytokines changes
IL-13 levels
Time frame: From baseline to 6 months
Cytokines changes
IL-10 levels
Time frame: From baseline to 6 months
Changes in the peripheral blood mononuclear cells
Th1 and Th17 subsets isolation and analyses
Time frame: From baseline to 6 months
Patients quality of life
Visual analogue scale (VAS) score for itch
Time frame: From baseline to 6 months
Patients quality of life
Chronic Liver Disease Questionnaire (CLDQ)
Time frame: From baseline to 6 months
Patients quality of life
EQ-5D-5L questionnaire
Time frame: From baseline to 6 months
Patients quality of life
PSC patient reported outcome (PSC-PRO) questionnaire
Time frame: From baseline to 6 months
Patients quality of life
Inflammatory Bowel Disease Questionnaire (IBDQ)
Time frame: From baseline to 6 months

Study locations

1 of 1 sites recruiting

Fondazione IRCCS San Gerardo dei Tintori
Monza, Monza E Brianza 20900, Italy
- Marco Carbone, MD · Contact · marco.carbone@unimib.it · 0392334515
Recruiting

References and documents

Publications

Cristoferi L, D'Amato D, Maino C, Bernasconi D, Dinelli ME, Malandrin SMI, Facciotti F, Vigano C, Pirola L, Festa MM, Gerussi A, Rossi E, Malinverno F, Tettamanti P, Cazzaniga ME, Corso R, Ippolito D, Galimberti S, Invernizzi P, Carbone M. Prospective, randomised, placebo-controlled, phase 2 clinical trial assessing the efficacy and safety of oral vancomycin in patients with primary sclerosing cholangitis with/out inflammatory bowel disease in Italy: study protocol of VanC-IT trial. BMJ Open. 2026 Jan 9;16(1):e106630. doi: 10.1136/bmjopen-2025-106630. PubMed 41513411 ↗

Individual participant data

Plan to share: No

Updates

Tracking since Sep 25, 2026

No changes since tracking began. The registry record was last updated on Jul 25, 2025, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗

Registry details

Key details

Study ID: NCT05876182
Lead sponsor: University of Milano Bicocca
Collaborators: Genetic s.p.a.
Responsible party: Sponsor
First posted: May 25, 2023
Start date: Jun 15, 2023
Primary completion: Jun 2026 (estimated)
Completion: Jun 2026 (estimated)
Last update: Jul 25, 2025

Study contacts

Marco Carbone, MD

Contact

marco.carbone@unimib.it

0392334515

Pietro Invernizzi, MD

Contact

pietro.invernizzi@unimib.it

039 233 2187

Oversight

FDA-regulated drug: No
FDA-regulated device: No

View the source record on ClinicalTrials.gov ↗

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