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Sulfasalazine for the Treatment of Primary Sclerosing Cholangitis (SHIP)

Primary Purpose

Primary Sclerosing Cholangitis

Status
Recruiting
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Sulfasalazine
Placebo
Sponsored by
Brigham and Women's Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Primary Sclerosing Cholangitis focused on measuring Sclerosing, Cholangitis

Eligibility Criteria

15 Years - 80 Years (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • University of California, DavisRecruiting
  • University of MiamiRecruiting
  • University of Chicago Medicine
  • Massachusetts General HospitalRecruiting
  • Brigham and Women's HospitalRecruiting
  • Henry Ford Health SystemRecruiting
  • Washington University in St. Louis
  • Duke University School of MedicineRecruiting
  • University of Cincinnati Medical Center
  • Hospital of the University of Pennsylvania
  • Baylor Scott & White Health
  • University of Washington Medical CenterRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

Active Drug (Sulfasalazine)

Placebo

Arm Description

Outcomes

Primary Outcome Measures

Reduction in Mean Alkaline Phosphatase (ALP)
Proportion of patients with reduction of mean ALP < 1.5 x ULN at end of treatment
Normalization of ALP below the upper limit of normal
Assessment in number of patients whose ALP normalizes

Secondary Outcome Measures

Overall changes in ALP levels
Proportion of patients with ALP > or < 1.5 x ULN at end of treatment
Changes in blood tests
Change in mean Liver Function Tests (e.g. Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT), total bilirubin) and C-reactive Protein
Adverse Events
Unexpected and Serious Adverse Events will be examined
Changes in Mayo PSC risk score
Number of patients with changes in Mayo PSC risk score
Changes in Modified Fatigue Scale (MFS)
Number of patients with changes in MFS score
Changes in pruritus visual analog scale (VAS)
Number of patients with changes in VAS score

Full Information

First Posted
May 14, 2018
Last Updated
March 4, 2022
Sponsor
Brigham and Women's Hospital
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1. Study Identification

Unique Protocol Identification Number
NCT03561584
Brief Title
Sulfasalazine for the Treatment of Primary Sclerosing Cholangitis
Acronym
SHIP
Official Title
A Randomized, Placebo-controlled Pilot Study of Sulfasalazine for the Treatment of Primary Sclerosing Cholangitis (PSC)
Study Type
Interventional

2. Study Status

Record Verification Date
March 2022
Overall Recruitment Status
Recruiting
Study Start Date
July 1, 2018 (Actual)
Primary Completion Date
March 1, 2023 (Anticipated)
Study Completion Date
May 1, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Brigham and Women's Hospital

4. Oversight

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
Data Monitoring Committee
Yes

5. 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Primary Sclerosing Cholangitis
Keywords
Sclerosing, Cholangitis

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Sequential Assignment
Model Description
There are two arms in this trial: active drug and placebo.
Masking
ParticipantCare 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.
Allocation
Randomized
Enrollment
42 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Active Drug (Sulfasalazine)
Arm Type
Active Comparator
Arm Title
Placebo
Arm Type
Placebo Comparator
Intervention Type
Drug
Intervention Name(s)
Sulfasalazine
Other Intervention Name(s)
Azulfidine
Intervention Description
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
Intervention Name(s)
Placebo
Intervention Description
Patients will be initiated on 1 placebo tablet twice daily (bid). Dosage will be increased throughout the study.
Primary Outcome Measure Information:
Title
Reduction in Mean Alkaline Phosphatase (ALP)
Description
Proportion of patients with reduction of mean ALP < 1.5 x ULN at end of treatment
Time Frame
Baseline through the end of the Study at Week 22
Title
Normalization of ALP below the upper limit of normal
Description
Assessment in number of patients whose ALP normalizes
Time Frame
Baseline through the end of the Study at Week 22
Secondary Outcome Measure Information:
Title
Overall changes in ALP levels
Description
Proportion of patients with ALP > or < 1.5 x ULN at end of treatment
Time Frame
Baseline through the end of the Study at Week 22
Title
Changes in blood tests
Description
Change in mean Liver Function Tests (e.g. Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT), total bilirubin) and C-reactive Protein
Time Frame
Baseline through the end of the Study at Week 22
Title
Adverse Events
Description
Unexpected and Serious Adverse Events will be examined
Time Frame
Baseline through the end of the Study at Week 22
Title
Changes in Mayo PSC risk score
Description
Number of patients with changes in Mayo PSC risk score
Time Frame
Baseline through the end of the Study at Week 22
Title
Changes in Modified Fatigue Scale (MFS)
Description
Number of patients with changes in MFS score
Time Frame
Baseline through the end of the Study at Week 22
Title
Changes in pruritus visual analog scale (VAS)
Description
Number of patients with changes in VAS score
Time Frame
Baseline through the end of the Study at Week 22

10. Eligibility

Sex
All
Minimum Age & Unit of Time
15 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Age 15-80 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. ALP > 1.67 times the upper limit of normal (ULN) at screening Inflammatory bowel disease 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: Anticipated need for liver transplant within one year as determined by Mayo PSC risk score treatment Evidence of decompensated liver disease such as variceal bleeding, ascites, or hepatic encephalopathy. Evidence of advanced liver disease including MELD score > 10, bilirubin > 3.0, platelet count < 100,000; or INR > 1.4 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 Secondary causes of sclerosing cholangitis Known intolerance to sulfasalazine (including but not limited to allergy to sulfa or mesalamine) or folic acid History of cholangiocarcinoma or colon cancer within 5 years History of colectomy with > 1/3 bowel resected Treatment with any investigational agents, within two months or 5 half-lives of the investigational product, whichever is longer. Active illicit drug or alcohol abuse Current or past use of sulfasalazine within 6 months of enrollment. Need for chronic use of antibiotics Evidence of bacterial cholangitis within 6 months of enrollment In patients with Ulcerative Colitis, simple clinical colitis activity index of > 4 or, if Crohn's disease, a Harvey-Bradshaw index of > 5 Chronic kidney injury (eGFR < 59) Pregnancy or lactation
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
S Fernanda Quevedo, BS
Phone
617-732-9173
Email
sfernandaquevedo@bwh.harvard.edu
First Name & Middle Initial & Last Name or Official Title & Degree
Kelleigh Youngclaus, BS, BS
Phone
6177327814
Email
kyoungclaus@bwh.harvard.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Joshua R Korzenik, MD
Organizational Affiliation
Brigham and Women's Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of California, Davis
City
Davis
State/Province
California
ZIP/Postal Code
95616
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Sandeep Dhaliwal
Phone
916-734-8696
Email
sandhaliwal@ucdavis.edu
First Name & Middle Initial & Last Name & Degree
Christopher L Bowlus, MD
Facility Name
University of Miami
City
Miami
State/Province
Florida
ZIP/Postal Code
33136
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Olivia I Blust
Phone
202-380-7102
Email
oib5@med.miami.edu
First Name & Middle Initial & Last Name & Degree
Cynthia Levy, MD
First Name & Middle Initial & Last Name & Degree
Diane Sabogal, NP
Facility Name
University of Chicago Medicine
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60637
Country
United States
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Kristi Kearney, RN
Phone
773-834-7414
Email
kkearney@medicine.bsd.uchicago.edu
First Name & Middle Initial & Last Name & Degree
Amy Duong
Email
aduong@medicine.bsd.uchicago.ed
First Name & Middle Initial & Last Name & Degree
Joel Pekow, MD
Facility Name
Massachusetts General Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jenna L Gustafson
Phone
617-724-3836
Email
jlgustafson@mgh.harvard.edu
First Name & Middle Initial & Last Name & Degree
Daniel S Pratt, M.D.
Facility Name
Brigham and Women's Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Fernanda Quevedo, BS
Phone
617-732-9173
Email
sfernandaquevedo@bwh.harvard.edu
First Name & Middle Initial & Last Name & Degree
Kelleigh Youngclaus, BS,BS
Phone
6177327814
Email
kyoungclaus@bwh.harvard.edu
First Name & Middle Initial & Last Name & Degree
Joshua Korzenik, MD
Facility Name
Henry Ford Health System
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48202
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jonathan Uhas
Phone
313-916-1967
Email
Juhas1@hfhs.org
First Name & Middle Initial & Last Name & Degree
Stuart C Gordon, MD
Facility Name
Washington University in St. Louis
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63105
Country
United States
Individual Site Status
Withdrawn
Facility Name
Duke University School of Medicine
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27710
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Christy Walters, RN
Phone
919-668-5499
Email
christy.walters@duke.edu
First Name & Middle Initial & Last Name & Degree
Andrew J Muir, MD
Facility Name
University of Cincinnati Medical Center
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45267
Country
United States
Individual Site Status
Suspended
Facility Name
Hospital of the University of Pennsylvania
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Individual Site Status
Completed
Facility Name
Baylor Scott & White Health
City
Dallas
State/Province
Texas
ZIP/Postal Code
75246
Country
United States
Individual Site Status
Terminated
Facility Name
University of Washington Medical Center
City
Seattle
State/Province
Washington
ZIP/Postal Code
98195
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Isabella Bueno
Phone
206-685-3008
Email
buenoi@medicine.washington.edu
First Name & Middle Initial & Last Name & Degree
James Kashima
Email
kashij@medicine.washington.edu
First Name & Middle Initial & Last Name & Degree
Kiran Bambha

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

Sulfasalazine for the Treatment of Primary Sclerosing Cholangitis

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