Detoxification of the Liver In PSC (Dolphin)
Purpose
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.
Condition
- Primary Sclerosing Cholangitis
Eligibility
- Eligible Ages
- Between 18 Years and 75 Years
- Eligible Genders
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- 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).
Exclusion Criteria
- 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
Study Design
- Phase
- Phase 2
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Crossover Assignment
- Intervention Model Description
- This a crossover study in which everyone will have a period of time on the active medication and a period of time on the placebo.
- Primary Purpose
- Treatment
- Masking
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
- Masking Description
- This is a double-blinded study.
Arm Groups
| Arm | Description | Assigned Intervention |
|---|---|---|
|
Active Comparator 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. |
|
|
Placebo Comparator 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. |
|
Recruiting Locations
Brigham and Women's Hospital
Chestnut Hill, Massachusetts 02467
Chestnut Hill, Massachusetts 02467
More Details
- Status
- Recruiting
- Sponsor
- Brigham and Women's Hospital