Using sulfasalazine to treat primary sclerosing cholangitis

A Randomized, Placebo-controlled Pilot Study of Sulfasalazine for the Treatment of Primary Sclerosing Cholangitis (PSC)

This study is testing if the medication sulfasalazine can help people with primary sclerosing cholangitis feel better and improve their liver health.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 42 (estimated)
• Ages: 15 Years to 80 Years
• Sex: All
• Sponsor: Brigham and Women's Hospital (Academic / other)
• Locations: 1 site (Chestnut Hill, Massachusetts)
• Trial ID: NCT03561584 on ClinicalTrials.gov

What this trial studies

This multicenter, randomized, double-blinded placebo-controlled trial aims to evaluate the effectiveness of sulfasalazine in treating primary sclerosing cholangitis (PSC). The study will assess whether sulfasalazine can reduce serum alkaline phosphatase (ALP) levels and other liver injury biomarkers, improve patient symptoms, and ensure safety for individuals with PSC. Given the association between PSC and inflammatory bowel disease (IBD), the trial hypothesizes that a medication effective for ulcerative colitis may also benefit PSC patients. Participants can be enrolled remotely from anywhere in the United States.

Who should consider this trial

Good fit: Ideal candidates include individuals aged 15-80 with a diagnosis of PSC for at least six months and concurrent inflammatory bowel disease.

Not a fit: Patients who are anticipated to need a liver transplant within one year or have evidence of advanced liver disease may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new therapeutic option for patients suffering from primary sclerosing cholangitis.

How similar studies have performed: While sulfasalazine has not been formally tested in PSC, some retrospective reports suggest potential benefits, indicating this approach is novel.

Eligibility criteria

Inclusion Criteria:

1. Age 15-80
2. A diagnosis of PSC for at least 6 months based upon cholangiography (ERCP or MRCP) demonstrating intrahepatic and/or extrahepatic biliary strictures, beading or irregularity consistent with PSC.
3. ALP \> 1.67 times the upper limit of normal (ULN) at screening
4. Inflammatory bowel disease
5. Subject must either be on a stable dose of ursodeoxycholic acid for \> 6 months prior to screening or have been discontinued \> 4 weeks prior to screening (enrollment of patients who are on UDCA will be limited to 50% of all enrolled patients).

We are recruiting remotely throughout the United States so an individual anywhere in the US with PSC and IBD can be enrolled.

Exclusion Criteria:

1. Anticipated need for liver transplant within one year as determined by Mayo PSC risk score treatment
2. Evidence of decompensated liver disease such as variceal bleeding, ascites, or hepatic encephalopathy.
3. Evidence of advanced liver disease including MELD score \> 10, bilirubin \> 3.0, platelet count \< 100,000; or INR \> 1.4
4. Concomitant chronic liver disease including alcohol related liver disease, chronic hepatitis B or C infection, haemochromatosis, Wilson's disease, alpha1-antitrypsin deficiency, non-alcoholic steatohepatitis, autoimmune hepatitis, or primary biliary cholangitis
5. Secondary causes of sclerosing cholangitis
6. Known intolerance to sulfasalazine (including but not limited to allergy to sulfa or mesalamine) or folic acid
7. History of cholangiocarcinoma or colon cancer within 5 years
8. History of colectomy with \> 1/3 bowel resected
9. Treatment with any investigational agents, within two months or 5 half-lives of the investigational product, whichever is longer.
10. Active illicit drug or alcohol abuse
11. Current or past use of sulfasalazine within 6 months of enrollment.
12. Need for chronic use of antibiotics
13. Evidence of bacterial cholangitis within 6 months of enrollment
14. In patients with Ulcerative Colitis, simple clinical colitis activity index of \> 4 or, if Crohn's disease, a Harvey-Bradshaw index of \> 5
15. Chronic kidney injury (eGFR \< 59)
16. Pregnancy or lactation

Where this trial is running

Chestnut Hill, Massachusetts

• Brigham and Women's Hospital — Chestnut Hill, Massachusetts, United States (Recruiting)

Study contacts

• Principal investigator: Joshua R Korzenik, MD — Brigham and Women's Hospital
• Study coordinator: Charu Madhwani Jain, MD, MPH

Conditions Primary Sclerosing Cholangitis; Sclerosing; Cholangitis