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SHIP: Sulfasalazine for the Treatment of Primary Sclerosing Cholangitis

Sponsor
Brigham and Women's Hospital (Other)
Overall Status
Recruiting
CT.gov ID
NCT03561584
Collaborator
(none)
42
Enrollment
12
Locations
2
Arms
58
Anticipated Duration (Months)
3.5
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
Phase 2

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.

Study Design

Study Type:
Interventional
Anticipated Enrollment :
42 participants
Allocation:
Randomized
Intervention Model:
Sequential Assignment
Intervention Model Description:
There are two arms in this trial: active drug and placebo.There are two arms in this trial: active drug and placebo.
Masking:
Double (Participant, Care Provider)
Masking Description:
Participants and Providers will be masked until Week 14. If a subject continues past week 14, the study becomes Open-Label and participants are given the option to continue on the active drug for an additional 8 weeks.
Primary Purpose:
Treatment
Official Title:
A Randomized, Placebo-controlled Pilot Study of Sulfasalazine for the Treatment of Primary Sclerosing Cholangitis (PSC)
Actual Study Start Date :
Jul 1, 2018
Anticipated Primary Completion Date :
Mar 1, 2023
Anticipated Study Completion Date :
May 1, 2023

Arms and Interventions

Arm Intervention/Treatment
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

    		•
    Placebo Comparator: Placebo

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

    Outcome Measures

    Primary Outcome Measures

    1. Reduction in Mean Alkaline Phosphatase (ALP) [Baseline through the end of the Study at Week 22]

      Proportion of patients with reduction of mean ALP < 1.5 x ULN at end of treatment

    2. Normalization of ALP below the upper limit of normal [Baseline through the end of the Study at Week 22]

      Assessment in number of patients whose ALP normalizes

    Secondary Outcome Measures

    1. Overall changes in ALP levels [Baseline through the end of the Study at Week 22]

      Proportion of patients with ALP > or < 1.5 x ULN at end of treatment

    2. Changes in blood tests [Baseline through the end of the Study at Week 22]

      Change in mean Liver Function Tests (e.g. Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT), total bilirubin) and C-reactive Protein

    3. Adverse Events [Baseline through the end of the Study at Week 22]

      Unexpected and Serious Adverse Events will be examined

    4. Changes in Mayo PSC risk score [Baseline through the end of the Study at Week 22]

      Number of patients with changes in Mayo PSC risk score

    5. Changes in Modified Fatigue Scale (MFS) [Baseline through the end of the Study at Week 22]

      Number of patients with changes in MFS score

    6. Changes in pruritus visual analog scale (VAS) [Baseline through the end of the Study at Week 22]

      Number of patients with changes in VAS score

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    15 Years to 80 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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).

    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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 University of California, Davis Davis California United States 95616
    2 University of Miami Miami Florida United States 33136
    3 University of Chicago Medicine Chicago Illinois United States 60637
    4 Massachusetts General Hospital Boston Massachusetts United States 02114
    5 Brigham and Women's Hospital Boston Massachusetts United States 02115
    6 Henry Ford Health System Detroit Michigan United States 48202
    7 Washington University in St. Louis Saint Louis Missouri United States 63105
    8 Duke University School of Medicine Durham North Carolina United States 27710
    9 University of Cincinnati Medical Center Cincinnati Ohio United States 45267
    10 Hospital of the University of Pennsylvania Philadelphia Pennsylvania United States 19104
    11 Baylor Scott & White Health Dallas Texas United States 75246
    12 University of Washington Medical Center Seattle Washington United States 98195

    Sponsors and Collaborators

    • Brigham and Women's Hospital

    Investigators

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

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Joshua Korzenik, Director, Crohn's and Colitis Center, Brigham and Women's Hospital
    ClinicalTrials.gov Identifier:
    NCT03561584
    Other Study ID Numbers:
    • 2018P000019
    First Posted:
    Jun 19, 2018
    Last Update Posted:
    Mar 18, 2022
    Last Verified:
    Mar 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    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
    Keywords provided by Joshua Korzenik, Director, Crohn's and Colitis Center, Brigham and Women's Hospital
    Sclerosing
    Cholangitis
    Additional relevant MeSH terms:
    Cholangitis
    Cholangitis, Sclerosing
    Sulfasalazine

    Study Results

    No Results Posted as of Mar 18, 2022