A Study Of Ursolic Acid For Primary Sclerosing Cholangitis
- Registration Number
- NCT03216876
- Lead Sponsor
- University of California, Davis
- Brief Summary
This is an open-label, active treatment trial to determine the pharmacokinetics of orally administered ursolic acid and to assess the potential efficacy and safety of ursolic acid in subjects with primary sclerosing cholangitis (PSC).
- Detailed Description
In the first phase of this trial, 6 healthy subjects and 2 PSC subjects will assigned to ursolic acid taken orally as a single dose of 40 mg, 80 mg, and 120 mg to determine the optimal dose in humans.
The second phase of this trial will involve 20 PSC subjects assigned to treatment with daily oral ursolic acid at the dose determined to be optimal in the first phase of the study. The treatment will last for 24 weeks with an off-treatment follow up of 28 weeks.
Recruitment & Eligibility
- Status
- WITHDRAWN
- Sex
- All
- Target Recruitment
- Not specified
- Male or female age 18 - 70 years of age
- PSC documented by typically cholangiogram findings of strictures and dilations with no evidence of a secondary cause of sclerosing cholangitis
- Serum alkaline phosphatase greater than 1.5 times the upper limit of the normal reference range at the UC Davis Health Systems Clinical Laboratory
- AST and ALT ≤ 10 x ULN
- Serum creatinine < 2.0 mg/dL
- Mayo Activity Index of < 2 (in those with ulcerative colitis or Crohn's colitis)
- Negative serum pregnancy test for female subjects of childbearing potential, agreement to use a highly effective method of contraception during heterosexual intercourse (females of childbearing potential), lactating females must agree to discontinue nursing before starting study treatment, and barrier contraception during heterosexual intercourse (males not vasectomized).
- Pregnancy
- Hepatic decompensation defined as ascites (or use of diuretics), episodes of hepatic encephalopathy, variceal bleeding or an INR > 1.2
- Positive HCV RNA or HBsAg, positive anti-mitochondrial antibody, alcohol consumption greater than 21oz/week for males or 14oz/week for females
- Clinically significant cardiac disease, history of cholangiocarcinoma, history of liver transplantation, history of cancers, other than non-melanomatous skin cancer, within 5 years prior to screening
- Ascending cholangitis within 60 days of screening
- Use of immunosuppressants including 6-mercaptopurine, azathioprine, methotrexate, mycophenolate mofetil, tacrolimus, cyclosporine, and anti-TNF or other biologics within 6 months of enrollment
- Use of antibiotics including vancomycin, metronidazole, or rifaximin within 60 days of enrollment
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Healthy Controls Ursolic acid Healthy subjects will assigned to ursolic acid taken orally as a single dose of 40 mg, 80 mg, and 120 mg PSC Single Dose Ursolic acid PSC subjects will assigned to ursolic acid taken orally as a single dose of 40 mg, 80 mg, and 120 mg PSC Multiple Dose Ursolic acid PSC subjects assigned to treatment with daily oral ursolic acid at the dose determined to be optimal in the first phase of the study. The treatment will last for 24 weeks with an off-treatment follow up of 28 weeks
- Primary Outcome Measures
Name Time Method Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] 24 hours Number of serious adverse events or Grade 3-4 biochemical abnormalities
- Secondary Outcome Measures
Name Time Method volume of distribution (Vd) 24 hours Measured in volume, The apparent volume in which a drug is distributed (i.e., the parameter relating drug concentration to drug amount in the body).
C-reactive Protein (CRP) 24 weks Change in CRP from baseline to 24 weeks.
Biochemical response 24 weeks Reduction in serum alkaline phosphatase by 50% or to within the normal reference range and change in alkaline phosphatase from day 0 to week 24.
Alanine aminotransferase (ALT) 24 weeks Change in ALT from baseline to 24 weeks
maximum plasma concentration (C¬max) 24 hours Measured in mass of drug/ volume of fluid, The peak plasma concentration of a drug after administration.
half-life (t1/2), 24 hours measured in time ,Time to reach Cmax.
clearance 24 hours Measured in Volume/ time, The volume of plasma cleared of the drug per unit time
Area under the concentration-time curve (AUC) 24 hours Measured in mass/(volume\*time), The integral of the concentration-time curve (after a single dose or in steady state).
Total bilirubin 24 weks Change in total bilirubin from baseline to 24 weeks.
Mayo Risk Score (MRS) 24 weks Change in MRS from baseline to 24 weeks.
Trial Locations
- Locations (1)
Univeristy of California Davis Medical Center
🇺🇸Sacramento, California, United States