A Study Of Ursolic Acid For Primary Sclerosing Cholangitis

Primary Sclerosing Cholangitis Clinical Trial

Official title:

An Open-Label Study Of Ursolic Acid For Primary Sclerosing Cholangitis

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT03216876
• Other study ID #: PSC-001
• Status: Withdrawn
• Phase: Phase 1
• First received: January 5, 2016
• Last updated: July 21, 2017
• Start date: September 2017
• Est. completion date: July 2019

Study information

• Verified date: July 2017
• Source: University of California, Davis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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 information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: July 2019
• Est. primary completion date: January 2019
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

Inclusion Criteria:

• 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).

Exclusion Criteria:

• 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

Related Conditions & MeSH terms

• Cholangitis
• Cholangitis, Sclerosing
• Primary Sclerosing Cholangitis

Intervention

Drug:
• Ursolic acid
Ursolic acid (UA) is a natural triterpenoid carboxylic acid, which has been studied for its anti-proliferative and anti-inflammatory activities.

Locations

Country	Name	City	State
United States	Univeristy of California Davis Medical Center	Sacramento	California

Sponsors (1)

Lead Sponsor	Collaborator
University of California, Davis

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]	Number of serious adverse events or Grade 3-4 biochemical abnormalities	24 hours
Secondary	maximum plasma concentration (C¬max)	Measured in mass of drug/ volume of fluid, The peak plasma concentration of a drug after administration.	24 hours
Secondary	half-life (t1/2),	measured in time ,Time to reach Cmax.	24 hours
Secondary	volume of distribution (Vd)	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).	24 hours
Secondary	clearance	Measured in Volume/ time, The volume of plasma cleared of the drug per unit time	24 hours
Secondary	Area under the concentration-time curve (AUC)	Measured in mass/(volume*time), The integral of the concentration-time curve (after a single dose or in steady state).	24 hours
Secondary	Alanine aminotransferase (ALT)	Change in ALT from baseline to 24 weeks	24 weeks
Secondary	Total bilirubin	Change in total bilirubin from baseline to 24 weeks.	24 weks
Secondary	C-reactive Protein (CRP)	Change in CRP from baseline to 24 weeks.	24 weks
Secondary	Mayo Risk Score (MRS)	Change in MRS from baseline to 24 weeks.	24 weks
Secondary	Biochemical response	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.	24 weeks