Sulfasalazine for the Treatment of Primary Sclerosing Cholangitis

NCT ID: NCT03561584

Last Updated: 2024-04-22

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 42 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-07-01
• Study Completion Date: 2024-11-01

Brief Summary

This is a multicenter, randomized, double-blinded placebo controlled trial to assess the benefit of sulfasalazine in the treatment of PSC. The specific objectives of this study are to determine if sulfasalazine treatment 1) results in reduced serum ALP and other biomarkers of liver injury in PSC; 2) improves PSC patient symptoms; and 3) is safe in patients with PSC.

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

Detailed Description

As there is a strong association between PSC and IBD, it is reasonable to hypothesize that a therapy of proven benefit for UC may prove to also be effective for PSC. Unfortunately, several therapies which are indicated for the treatment of UC have not been effective in PSC including anti-TNF therapies and other anti-inflammatory medications. Sulfasalazine and mesalamine, medications commonly used for the treatment of UC, may be exceptions to this trend. While this therapy has never been formally tested in PSC, some retrospective reports suggest a possible benefit. Our current understanding of the mechanism of action of these medications suggests there is reasonable to believe they may also be effective in PSC.

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

Conditions

Primary Sclerosing Cholangitis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Active Drug (Sulfasalazine)

Group Type: ACTIVE_COMPARATOR

Sulfasalazine

Intervention Type: DRUG

Patients will be initiated on a low dose of sulfasalazine (500 mg) twice daily (bid). Dosage will be increased throughout the study.

Placebo

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Patients will be initiated on 1 placebo tablet twice daily (bid). Dosage will be increased throughout the study.

Interventions

Sulfasalazine

Patients will be initiated on a low dose of sulfasalazine (500 mg) twice daily (bid). Dosage will be increased throughout the study.

Intervention Type: DRUG

Placebo

Patients will be initiated on 1 placebo tablet twice daily (bid). Dosage will be increased throughout the study.

Intervention Type: DRUG

Other Intervention Names

Azulfidine

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

• Minimum Eligible Age: 15 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Brigham and Women's Hospital

OTHER

Sponsor Role: lead

Responsible Party

Joshua Korzenik

Director, Crohn's and Colitis Center

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Joshua R Korzenik, MD

Role: PRINCIPAL_INVESTIGATOR

Brigham and Women's Hospital

Locations

Brigham and Women's Hospital

Chestnut Hill, Massachusetts, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Charu Madhwani Jain, MD, MPH

Role: CONTACT

cmjain@bwh.harvard.edu

617-732-9119

Marin Waddington, BS, BS

Role: CONTACT

mwaddington@bwh.harvard.edu

6177329451

Facility Contacts

Sophie Mitchell

Role: primary

smitchell22@bwh.harvard.edu

617-732-9451

Marin Waddington

Role: backup

mwaddington@bwh.harvard.edu

6177329451

Other Identifiers

2018P000019

Identifier Type: -

Identifier Source: org_study_id