Sulfasalazine for the Treatment of Primary Sclerosing Cholangitis (SHIP)

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

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.

Study Overview

• Status: Recruiting
• Conditions: Primary Sclerosing Cholangitis
• Intervention / Treatment: Drug: Sulfasalazine; Drug: Placebo

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.

• Study Type: Interventional
• Enrollment (Estimated): 42
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Charu Madhwani Jain, MD, MPH; Phone Number: 617-732-9119; Email: cmjain@bwh.harvard.edu
• Study Contact Backup: Name: Marin Waddington, BS, BS; Phone Number: 6177329451; Email: mwaddington@bwh.harvard.edu

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Recruiting
      • Charu Madhwani Jain
      • Principal Investigator: Joshua Korzenik, MD
      • Contact: Charu Madhwani Jain, MD, MPH; Phone Number: 617-732-9119; Email: cmjain@bwh.harvard.edu
      • Contact: Marin Waddington, BS,BS; Phone Number: 6177329451; Email: mwaddington@bwh.harvard.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 15 years to 80 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo; Patients will be initiated on 1 placebo tablet twice daily (bid). Dosage will be increased throughout the study.
Active Comparator: Active Drug (Sulfasalazine)	Drug: Sulfasalazine; Patients will be initiated on a low dose of sulfasalazine (500 mg) twice daily (bid). Dosage will be increased throughout the study.; Other Names: Azulfidine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
Adverse Events	Unexpected and Serious Adverse Events will be examined	Baseline through the end of the Study at Week 22
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
Changes in Modified Fatigue Scale (MFS)	Number of patients with changes in MFS score	Baseline through the end of the Study at Week 22
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

Collaborators and Investigators

• Sponsor: Brigham and Women's Hospital
• Investigators: Principal Investigator: Joshua R Korzenik, MD, Brigham and Women's Hospital

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2018
• Primary Completion (Estimated): September 1, 2024
• Study Completion (Estimated): November 1, 2024

Study Registration Dates

• First Submitted: May 14, 2018
• First Submitted That Met QC Criteria: June 7, 2018
• First Posted (Actual): June 19, 2018

Study Record Updates

• Last Update Posted (Actual): December 18, 2023
• Last Update Submitted That Met QC Criteria: December 12, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Keywords: Cholangitis; Sclerosing
• Additional Relevant MeSH Terms: Digestive System Diseases; Biliary Tract Diseases; Bile Duct Diseases; Cholangitis; Cholangitis, Sclerosing; Physiological Effects of Drugs; Anti-Infective Agents; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Gastrointestinal Agents; Sulfasalazine
• Other Study ID Numbers: 2018P000019

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No