FAecal Microbiota Transplantation in primaRy sclerosinG chOlangitis

NCT06286709 | Recruiting Phase 2 DMC

• 1 other identifier: RG_22-063
• Study Type: interventional
• Target: 58
• Locations: 1 country
• Sites: 5

Brief Summary

FARGO is a randomised, phase IIa, multi-centre, placebo-controlled trial to compare Faecal Microbiota Transplant (FMT) with placebo in patients with primary sclerosing cholangitis (PSC) and concomitant inflammatory bowel disease.

Conditions

Primary Sclerosing Cholangitis; Inflammatory Bowel Diseases

Outcome Measures

Primary Outcomes (1)

• Serum Alkaline Phosphatase (ALP)

  Reduction in serum ALP values from baseline, measured at 48 weeks following the first dose of FMT or FMT Placebo.

  ALP at Screening (Week -2), Week 1, Week 3, Week 5, Week 8, Week 12, Week 24, Week 36 and Week 48

Secondary Outcomes (19)

• Patient-reported outcome (PRO) measures

  PSC-PRO at Screening (Week -2), Week 8, Week 12, Week 24, Week 36 and Week 48

• Patient-reported outcome (PRO) measures

  SF-36 at Screening (Week -2), Week 8, Week 12, Week 24, Week 36 and Week 48

• Patient-reported outcome (PRO) measures

  5D-Itch at Screening (Week -2), Week 8, Week 12, Week 24, Week 36 and Week 48

• Patient-reported outcome (PRO) measures

  SIBDQ at Screening (Week -2), Week 8, Week 12, Week 24, Week 36 and Week 48

• Surrogate biomarkers of liver fibrosis

  Surrogate biomarkers of liver fibrosis: VCTE at Screening (Week -2) and Week 48

Study Arms (2)

Faecal Microbiota Transplant (FMT)

ACTIVE COMPARATOR

FMT is 50mL aliquots of filtered suspension of stool (0.6g/mL). FMT for administration via colonoscopy will be made up of 150g stool in 250mL (5 aliquots). FMT for administration via enema will be made up of 30g stool in 50mL (1 aliquot) made up to 100mL by the addition of 50mL normal saline

Biological: Faecal Microbiota Transplant

FMT Placebo

PLACEBO COMPARATOR

FMT Placebo is 50mL aliquots of 0.9% w/v saline and glycerol in a ratio of 9 parts saline: 1 part glycerol v/v.

Other: FMT Placebo

Interventions

Faecal Microbiota Transplant BIOLOGICAL

FMT is 50mL aliquots of filtered suspension of stool (0.6g/mL). FMT for administration via colonoscopy will be made up of 150g stool in 250mL (5 aliquots). FMT for administration via enema will be made up of 30g stool in 50mL (1 aliquot) made up to 100mL by the addition of 50mL normal saline

Faecal Microbiota Transplant (FMT)

FMT Placebo OTHER

FMT Placebo is 50mL aliquots containing 0.9% w/v saline and glycerol in a ratio of 9 parts saline: 1 part glycerol v/v. FMT Placebo for administration via colonoscopy will be made up of 250mL (5 aliquots). FMT Placebo for administration via enema will be made up of 50mL (1 aliquot) made up to 100mL by the addition of 50mL normal saline

FMT Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Written informed consent
• Age ≥ 18 years
• Participants must be able to understand and comply with the purpose and procedures that are involved in the trial
• An established diagnosis of colonic inflammatory bowel disease, with willingness to participate in an annual colonoscopic surveillance program, as per routine standard of care
• An established clinical diagnosis of large duct PSC, with compatible features as assessed by magnetic resonance cholangiopancreatography (MRCP) or endoscopic retrograde cholangiopancreatography (ERCP)
• A persistent ALP value above normal (at least 2 readings at this value over 6 months before screening)
• Evidence of early to moderate stage liver fibrosis, as suspected by any of the following:
• Median VCTE score of ≤14.4kPa, with an interquartile range ≤30%
• Previous liver biopsy indicating at an absence of established cirrhosis, Ishak fibrosis stage \<IV (or equivalent) in the last 24 months
• Serum enhanced liver fibrosis score (ELF) ≤9.8
• A colonoscopy showing no evidence of dysplasia/neoplasia within 24 months before screening
• No evidence of active colitis, as evidenced by a Partial Mayo Score of ≤4, with a score of \<2 on the rectal bleeding domain at screening
• Individuals with IBD who are receiving treatment with biologics, immunosuppression or corticosteroids must be taking a stable dose for at least twelve weeks prior to screening, and be expected to remain on the same medication/same dose for the duration of the trial
• Individuals with PSC having overlapping features of autoimmune hepatitis may be included, provided:
• The dosage of immunosuppression has remained stable for at least twelve weeks prior to screening, and be expected to remain on the same medication/same dose for the duration of the trial; and

You may not qualify if:

• Secondary causes of sclerosing cholangitis including, but not limited to, IgG4-related cholangitis, cholangiopathy due to acquired immunodeficiency syndrome, drug-induced sclerosing cholangitis, trauma, ischaemic cholangiopathy, choledocholithiasis (investigator discretion), or sclerosing cholangiopathy as a sequelae of hepatopancreatobiliary resection
• Other causes of liver disease, including, but not limited to, IgG4-related disease; viral hepatitis; alcohol-related liver disease; clinically significant metabolic associated fatty liver disease (at investigator discretion); drug-induced liver disease; hereditary haemochromatosis; alpha-1-antitrypsin disease; primary biliary cholangitis; Wilson disease; Budd-Chiari Syndrome; or primary or secondary hepatopancreatobiliary cancer
• Presence of a clinically significant dominant stricture based on the combination of radiological, biochemical and clinical features. Patients can be included in the trial with a dominant extrahepatic stenosis if it has been stable for 6 months or more (as evidenced on imaging and also clinically), and one of the following are satisfied:
• The PI does not plan for any biliary intervention (endoscopic, percutaneous or surgical) for the duration of the trial OR
• The investigator decides that they do not wish to perform any biliary intervention (endoscopic, percutaneous or surgical) on the dominant stenosis for clinical reasons of stability/patient choice
• Presence of a percutaneous drain or bile duct stent
• Evidence of hepatic decompensation within twelve weeks prior to screening; or concern by the Principal Investigator that the participant may decompensate during the trial period. Hepatic decompensation as evidenced by variceal haemorrhage, ascites, hepatic hydrothorax, or hepatic encephalopathy (Appendix 1)
• Biochemical/laboratory evidence of very advanced hepatic dysfunction, as evidenced by a serum bilirubin value \>55 µmol/L (unless Gilbert Syndrome or another condition associated with unconjugated hyperbilirubinaemia, including but not limited to, spherocytosis and disorders of bilirubin conjugation where a bilirubin value\>45 µmol/L is allowable), serum albumin \<32 g/L, platelet level of \<140x109/L, Child-Turcotte-Pugh (CTP) score \>B7, or a MELD score \>15
• Ascending cholangitis as assessed clinically within twelve weeks of screening
• Use of antibiotics within twelve weeks of screening
• Participant already listed for liver transplantation, or concerns (investigator discretion) that they may need to be listed for liver transplantation during the trial period
• Small duct PSC
• Advanced-stage liver fibrosis, as evidenced by a VCTE score \>14.4kPa, a liver biopsy showing \>Ishak stage III fibrosis (or equivalent)
• Significant renal dysfunction as evidenced by an estimated glomerular filtration rate of \<60 ml/min according to the Cockcroft-Gault formula, or need for dialysis
• Human Immunodeficiency Virus (HIV) infection

Sponsors & Collaborators

• University of Birmingham: lead
• PSC Support: collaborator
• Life Arc: collaborator

Study Sites (5)

Queen Elizabeth Hospital Birmingham, University Hospitals Birmingham NHS Foundation Trust

Birmingham, B15 2TH, United Kingdom

RECRUITING

St Mark's Hospital, London North West University Healthcare NHS Trust

London, NW10 7NS, United Kingdom

RECRUITING

Royal Free Hospital, Royal Free London NHS Foundation Trust

London, NW3 2QG, United Kingdom

RECRUITING

King's College Hospital, King's College Hospital NHS Foundation Trust

London, SE5 9RS, United Kingdom

RECRUITING

John Radcliffe Hospital, Oxford University Hospitals NHS Foundation Trust

Oxford, OX3 9DU, United Kingdom

RECRUITING

Related Publications (1)

• Al-Shakhshir S, Quraishi MN, Mullish B, Patel A, Vince A, Rowe A, Homer V, Jackson N, Gyimah D, Shabir S, Manzoor S, Cooney R, Alrubaiy L, Quince C, van Schaik W, Hares M, Beggs AD, Efstathiou E, Rimmer P, Weston C, Iqbal T, Trivedi PJ. FAecal micRobiota transplantation in primary sclerosinG chOlangitis (FARGO): study protocol for a randomised, multicentre, phase IIa, placebo-controlled trial. BMJ Open. 2025 Jan 6;15(1):e095392. doi: 10.1136/bmjopen-2024-095392.

  PMID: 39762111 DERIVED

MeSH Terms

Conditions

Cholangitis, Sclerosing; Inflammatory Bowel Diseases

Condition Hierarchy (Ancestors)

Cholangitis; Bile Duct Diseases; Biliary Tract Diseases; Digestive System Diseases; Gastroenteritis; Gastrointestinal Diseases; Intestinal Diseases

Central Study Contacts

Helen Coulthard

CONTACT

+44 (0121) 3718198; FARGO@trials.bham.ac.uk

Anna Rowe

CONTACT

+44 (0121) 3718117; FARGO@trials.bham.ac.uk

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: Single-blind
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Phase IIa, multi-centre, randomised, placebo-controlled, single-blinded, parallel group, clinical trial

Study Record Dates

• First Submitted: February 7, 2024
• First Posted: February 29, 2024
• Study Start: March 27, 2024
• Primary Completion: April 30, 2026
• Study Completion (Estimated): February 28, 2027
• Last Updated: April 29, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL

Locations

GB (5)