Clinical trial NCT03561584: Sulfasalazine for the Treatment of Primary Sclerosing Cholangitis
Official title: A Randomized, Placebo-controlled Pilot Study of Sulfasalazine for the Treatment of Primary Sclerosing Cholangitis (PSC)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Primary Sclerosing Cholangitis
Keywords: Sclerosing
Cholangitis
Lead sponsor: Brigham and Women's Hospital
Sponsor class: OTHER
First posted: 2018-06-19
Enrollment: 42
Sex: ALL
Minimum age (years): 15
Maximum age (years): 80
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: There are two arms in this trial: active drug and placebo. We are recruiting remotely throughout the United States so an individual anywhere in the US with PSC and IBD can be enrolled.
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Reduction in Mean Alkaline Phosphatase (ALP)
timeFrame: Baseline through the end of the Study at Week 22
measure: Normalization of ALP below the upper limit of normal
timeFrame: Baseline through the end of the Study at Week 22
Secondary outcomes:
measure: Overall changes in ALP levels
timeFrame: Baseline through the end of the Study at Week 22
measure: Changes in blood tests
timeFrame: Baseline through the end of the Study at Week 22
measure: Adverse Events
timeFrame: Baseline through the end of the Study at Week 22
measure: Changes in Mayo PSC risk score
timeFrame: Baseline through the end of the Study at Week 22
measure: Changes in Modified Fatigue Scale (MFS)
timeFrame: Baseline through the end of the Study at Week 22
measure: Changes in pruritus visual analog scale (VAS)
timeFrame: Baseline through the end of the Study at Week 22
Other outcomes:
Locations:
city: Chestnut Hill
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
Study officials:
affiliation: Brigham and Women's Hospital
name: Joshua R Korzenik, MD
role: PRINCIPAL_INVESTIGATOR
References: