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Trial record 23 of 64 for:    "Bile Duct Disease" | "Anti-Infective Agents"

A Study Of Ursolic Acid For Primary Sclerosing Cholangitis

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ClinicalTrials.gov Identifier: NCT03216876
Recruitment Status : Withdrawn (Lack of feasibility)
First Posted : July 13, 2017
Last Update Posted : July 25, 2017
Sponsor:
Information provided by (Responsible Party):
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).

Condition or disease Intervention/treatment Phase
Primary Sclerosing Cholangitis Drug: Ursolic acid Phase 1

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.


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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 0 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: An Open-Label Study Of Ursolic Acid For Primary Sclerosing Cholangitis
Estimated Study Start Date : September 2017
Estimated Primary Completion Date : January 2019
Estimated Study Completion Date : July 2019


Arm Intervention/treatment
Experimental: Healthy Controls
Healthy subjects will assigned to ursolic acid taken orally as a single dose of 40 mg, 80 mg, and 120 mg
Drug: Ursolic acid
Ursolic acid (UA) is a natural triterpenoid carboxylic acid, which has been studied for its anti-proliferative and anti-inflammatory activities.
Other Names:
  • urson
  • prunol
  • malol
  • 3-beta-3-hydroxy-urs-12-ene-28-oic-acid

Experimental: PSC Single Dose
PSC subjects will assigned to ursolic acid taken orally as a single dose of 40 mg, 80 mg, and 120 mg
Drug: Ursolic acid
Ursolic acid (UA) is a natural triterpenoid carboxylic acid, which has been studied for its anti-proliferative and anti-inflammatory activities.
Other Names:
  • urson
  • prunol
  • malol
  • 3-beta-3-hydroxy-urs-12-ene-28-oic-acid

Experimental: PSC Multiple Dose
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
Drug: Ursolic acid
Ursolic acid (UA) is a natural triterpenoid carboxylic acid, which has been studied for its anti-proliferative and anti-inflammatory activities.
Other Names:
  • urson
  • prunol
  • malol
  • 3-beta-3-hydroxy-urs-12-ene-28-oic-acid




Primary Outcome Measures :
  1. Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] [ Time Frame: 24 hours ]
    Number of serious adverse events or Grade 3-4 biochemical abnormalities


Secondary Outcome Measures :
  1. maximum plasma concentration (C¬max) [ Time Frame: 24 hours ]
    Measured in mass of drug/ volume of fluid, The peak plasma concentration of a drug after administration.

  2. half-life (t1/2), [ Time Frame: 24 hours ]
    measured in time ,Time to reach Cmax.

  3. volume of distribution (Vd) [ Time Frame: 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).

  4. clearance [ Time Frame: 24 hours ]
    Measured in Volume/ time, The volume of plasma cleared of the drug per unit time

  5. Area under the concentration-time curve (AUC) [ Time Frame: 24 hours ]
    Measured in mass/(volume*time), The integral of the concentration-time curve (after a single dose or in steady state).

  6. Alanine aminotransferase (ALT) [ Time Frame: 24 weeks ]
    Change in ALT from baseline to 24 weeks

  7. Total bilirubin [ Time Frame: 24 weks ]
    Change in total bilirubin from baseline to 24 weeks.

  8. C-reactive Protein (CRP) [ Time Frame: 24 weks ]
    Change in CRP from baseline to 24 weeks.

  9. Mayo Risk Score (MRS) [ Time Frame: 24 weks ]
    Change in MRS from baseline to 24 weeks.

  10. Biochemical response [ Time Frame: 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.



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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03216876


Locations
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United States, California
Univeristy of California Davis Medical Center
Sacramento, California, United States, 95817
Sponsors and Collaborators
University of California, Davis
Investigators
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Principal Investigator: Christopher Bowlus, MD University of California, Davis

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Responsible Party: University of California, Davis
ClinicalTrials.gov Identifier: NCT03216876     History of Changes
Other Study ID Numbers: PSC-001
First Posted: July 13, 2017    Key Record Dates
Last Update Posted: July 25, 2017
Last Verified: July 2017

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Bile Duct Diseases
Anti-Infective Agents
Cholangitis
Cholangitis, Sclerosing
Biliary Tract Diseases
Digestive System Diseases
Ursolic acid
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Cyclooxygenase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Inflammatory Agents
Antirheumatic Agents