Detoxification of the Liver in Primary Sclerosing Cholangitis
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 28
- 试验地点
- 1
- 主要终点
- Alkaline Phosphatase (ALP) Test Result
研究概览
简要总结
This study is a clinical trial being done to investigate the efficacy of drug BRS201 (hydroxocobalamin) as a treatment in patients with primary sclerosing cholangitis. Participation in this study will take 8 weeks long and the study is structured as a cross-over study in which participants will take the study drug for 4 weeks and a placebo drug for 4 weeks in a randomized order in the form of an oral medication. Participation may also involve receiving an IV dose of the medication. The study will require participants to attend 9 study visits, all of which will be remote. Participation will involve taking an oral medication twice daily, tracking the medication in a log, and getting blood drawn and giving a stool sample for a few lab tests throughout the study. For the lab tests, a research nurse will visit the participant in-home for the convenience of the participant.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
This is a double-blinded study.
入排标准
- 年龄范围
- 18 Years 至 75 Years（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 > 1.5 times the upper limit of normal (ULN) at screening.
- •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 60% of all enrolled patients).
排除标准
- •Anticipated need for liver transplant within one year as determined by Mayo PSC risk score
- •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
- •Patients who have a confirmed malignancy or cancer within 5 years except non-melanoma skin cancers
- •Treatment with any investigational agents, within two months or 5 half-lives of the investigational product, whichever is longer.
- •Active illicit drug or more than moderate alcohol consumption.
- •Evidence of bacterial cholangitis within 6 months of enrollment
- •In patients with Ulcerative Colitis, or, if Crohn's disease, a need for additional therapy at time of screening.
- •Chronic kidney injury (eGFR < 60)
- •Pregnancy or lactation
- •Uncontrolled hypertension with a systolic BP > 140 and a systolic BP > 90
- •Prohibited medications: current use of vitamin C and prednisone
- •Patients with a history or risk of cardiovascular conditions, including arrhythmia, long QT syndrome, congestive heart failure, stroke, or coronary artery disease
- •Patients with a history of kidney stones
- •Congenital or acquired immunodeficiencies
- •Other comorbidities including: diabetes mellitus, systemic lupus
- •An episode of acute cholangitis within 4 weeks of screening Check eligibility here: https://redcap.link/Checkmyeligibility
研究组 & 干预措施
Placebo Arm
In Group 1 of the study, subjects will take oral placebo at 1.2g twice daily, PO (2.4g daily) for 4 weeks.
In Group 2 of the study, subjects will take oral placebo at 2g twice daily, PO (4g daily) for 4 weeks.
In Group 3 of the study, subjects will take receive a one-time 5g IV dose of the study drug using the FDA-approved IV product followed by the oral placebo at 2g twice daily, PO (4g daily) for 4 weeks.
In Group 4 of the study, subjects will repeat the previous conditions of the group that proves to be the most effective.
干预措施: Placebo (Drug)
BRS201 Arm
In Group 1 of the study, subjects will take oral study drug at 1.2g twice daily, PO (2.4g daily) for 4 weeks.
In Group 2 of the study, subjects will take oral study drug at 2g twice daily, PO (4g daily) for 4 weeks.
In Group 3 of the study, subjects will take receive a one-time 5g IV dose of the study drug using the FDA-approved IV product followed by the oral study drug at 2g twice daily, PO (4g daily) for 4 weeks.
In Group 4 of the study, subjects will repeat the previous conditions of the group that proves to be the most effective.
干预措施: BRS201 (Drug)
结局指标
主要结局
Alkaline Phosphatase (ALP) Test Result
时间窗: 4 weeks
The primary endpoint for this study is the capacity of BRS201 to normalize alkaline phosphatase levels from baseline (week 0) compared to end of active treatment (4 weeks).
次要结局
未报告次要终点
研究者
Joshua Korzenik
Director, Crohn's and Colitis Center
Brigham and Women's Hospital