Sulfasalazine for the Treatment of Primary Sclerosing Cholangitis

Primary Sclerosing Cholangitis Clinical Trial

— SHIP  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03561584
• Other study ID #: 2018P000019
• Status: Recruiting
• Phase: Phase 2
• Start date: July 1, 2018
• Est. completion date: November 1, 2024

Study information

• Verified date: December 2023
• Source: Brigham and Women's Hospital
• Contact: Charu Madhwani Jain, MD, MPH
• Phone: 617-732-9119
• Email: cmjain[@]bwh.harvard.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 42
• Est. completion date: November 1, 2024
• Est. primary completion date: September 1, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 15 Years to 80 Years

Eligibility

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

Related Conditions & MeSH terms

• Cholangitis
• Cholangitis, Sclerosing
• Primary Sclerosing Cholangitis

Intervention

Drug:
• Sulfasalazine
Patients will be initiated on a low dose of sulfasalazine (500 mg) twice daily (bid). Dosage will be increased throughout the study.
• Placebo
Patients will be initiated on 1 placebo tablet twice daily (bid). Dosage will be increased throughout the study.

Locations

Country	Name	City	State
United States	Brigham and Women's Hospital	Chestnut Hill	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
Brigham and Women's Hospital

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Reduction in Mean Alkaline Phosphatase (ALP)	Proportion of patients with reduction of mean ALP < 1.5 x ULN at end of treatment	Baseline through the end of the Study at Week 22
Primary	Normalization of ALP below the upper limit of normal	Assessment in number of patients whose ALP normalizes	Baseline through the end of the Study at Week 22
Secondary	Overall changes in ALP levels	Proportion of patients with ALP > or < 1.5 x ULN at end of treatment	Baseline through the end of the Study at Week 22
Secondary	Changes in blood tests	Change in mean Liver Function Tests (e.g. Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT), total bilirubin) and C-reactive Protein	Baseline through the end of the Study at Week 22
Secondary	Adverse Events	Unexpected and Serious Adverse Events will be examined	Baseline through the end of the Study at Week 22
Secondary	Changes in Mayo PSC risk score	Number of patients with changes in Mayo PSC risk score	Baseline through the end of the Study at Week 22
Secondary	Changes in Modified Fatigue Scale (MFS)	Number of patients with changes in MFS score	Baseline through the end of the Study at Week 22
Secondary	Changes in pruritus visual analog scale (VAS)	Number of patients with changes in VAS score	Baseline through the end of the Study at Week 22