Clinical trial NCT05835505: Detoxification of the Liver In PSC (Dolphin)
Official title: Detoxification of the Liver in Primary Sclerosing Cholangitis
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Primary Sclerosing Cholangitis
Lead sponsor: Brigham and Women's Hospital
Sponsor class: OTHER
First posted: 2023-04-28
Enrollment: 28
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
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

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: Alkaline Phosphatase (ALP) Test Result
timeFrame: 4 weeks
Secondary outcomes:
Other outcomes:
Locations:
city: Chestnut Hill
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
Study officials:
affiliation: Brigham and Womens Hospital
name: Joshua A Korzenik, MD
role: PRINCIPAL_INVESTIGATOR
References: