A Randomized, Placebo-controlled Pilot Study of Sulfasalazine for the Treatment of Primary Sclerosing Cholangitis (PSC)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 32
- 试验地点
- 1
- 主要终点
- Reduction in Mean Alkaline Phosphatase (ALP)
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- Double (Participant, Care Provider)
盲法说明
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. We are recruiting remotely throughout the United States so an individual anywhere in the US with PSC and IBD can be enrolled.
入排标准
- 年龄范围
- 15 Years 至 80 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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).
- •We are recruiting remotely throughout the United States so an individual anywhere in the US with PSC and IBD can be enrolled.
排除标准
- •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
研究组 & 干预措施
Active Drug (Sulfasalazine)
干预措施: Sulfasalazine (Drug)
Placebo
干预措施: Placebo (Drug)
结局指标
主要结局
Reduction in Mean Alkaline Phosphatase (ALP)
时间窗: 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
Normalization of ALP below the upper limit of normal
时间窗: Baseline through the end of the Study at Week 22
Assessment in number of patients whose ALP normalizes
次要结局
- Overall changes in ALP levels(Baseline through the end of the Study at Week 22)
- Changes in blood tests(Baseline through the end of the Study at Week 22)
- Adverse Events(Baseline through the end of the Study at Week 22)
- Changes in Mayo PSC risk score(Baseline through the end of the Study at Week 22)
- Changes in Modified Fatigue Scale (MFS)(Baseline through the end of the Study at Week 22)
- Changes in pruritus visual analog scale (VAS)(Baseline through the end of the Study at Week 22)
研究者
Joshua Korzenik
Director, Crohn's and Colitis Center
Brigham and Women's Hospital