Primary Sclerosing CholangitisPhase 1NCT03216876
A Study Of Ursolic Acid For Primary Sclerosing Cholangitis
A Phase 1 study testing Ursolic acid in people with Primary Sclerosing Cholangitis, run by University of California, Davis at 1 site in United States.
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). Read more about this study
- Who is it for?
- Ages 18 to 70 yearsHealthy volunteers can take part
- Conditions the study is for
- Primary Sclerosing Cholangitis
- What is being tested?
- Ursolic acid
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 1 siteUnited States
- Study dates
- Sep 2017to Jul 2019
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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).
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
Univeristy of California Davis Medical Center
Sacramento, California, 95817
About this study
Official title: An Open-Label Study Of Ursolic Acid For Primary Sclerosing Cholangitis
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).
Read the 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.
- Conditions
- Primary Sclerosing Cholangitis
- Being tested
- Ursolic acid
- Medical subject headings
- Cholangitis, Sclerosing
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Ursolic acidDrug
Also called urson, prunol, malol, 3-beta-3-hydroxy-urs-12-ene-28-oic-acid
Ursolic acid (UA) is a natural triterpenoid carboxylic acid, which has been studied for its anti-proliferative and anti-inflammatory activities.
| Study group | Role | What they receive |
|---|---|---|
| Healthy Controls | Experimental | Healthy subjects will assigned to ursolic acid taken orally as a single dose of 40 mg, 80 mg, and 120 mg Receives: Drug: Ursolic acid |
| PSC Single Dose | Experimental | PSC subjects will assigned to ursolic acid taken orally as a single dose of 40 mg, 80 mg, and 120 mg Receives: Drug: Ursolic acid |
| PSC Multiple Dose | Experimental | 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 Receives: Drug: Ursolic acid |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]
Number of serious adverse events or Grade 3-4 biochemical abnormalities
Measured: 24 hours
Secondary outcomes (10)
maximum plasma concentration (C¬max)
Measured in mass of drug/ volume of fluid, The peak plasma concentration of a drug after administration.
Measured: 24 hours
half-life (t1/2),
measured in time ,Time to reach Cmax.
Measured: 24 hours
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).
Measured: 24 hours
clearance
Measured in Volume/ time, The volume of plasma cleared of the drug per unit time
Measured: 24 hours
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).
Measured: 24 hours
Alanine aminotransferase (ALT)
Change in ALT from baseline to 24 weeks
Measured: 24 weeks
Total bilirubin
Change in total bilirubin from baseline to 24 weeks.
Measured: 24 weks
C-reactive Protein (CRP)
Change in CRP from baseline to 24 weeks.
Measured: 24 weks
Mayo Risk Score (MRS)
Change in MRS from baseline to 24 weeks.
Measured: 24 weks
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.
Measured: 24 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Jul 2017
- Study startSep 2017 (estimated)
- Primary completionJan 2019 (estimated)
- Study completionJul 2019 (estimated)
Why it stopped: Lack of feasibility
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Primary Sclerosing CholangitisStudies of the same condition, open and under way.
- More trials run by University of California, DavisThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of California, Davis
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Christopher Bowlus, MD, Principal investigator, University of California, Davis
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03216876
- Sponsor's protocol ID
- PSC-001
- Status last verified
- Jul 2017
- First submitted
- 5 Jan 2016
- Last updated
- 25 Jul 2017
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 25 Jul 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-Label Study Of Ursolic Acid For Primary Sclerosing Cholangitis
- ClinicalTrials.gov ID
- NCT03216876
- Acronym / sponsor ID
- PSC-001
- Conditions
- Primary Sclerosing Cholangitis
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Lack of feasibility
- Enrolment
- 0 participants (actual)
- Lead sponsor
- University of California, DavisUniversity, hospital or other
- Study start
- Sep 2017 (estimated)
- Primary completion
- Jan 2019 (estimated)
- Study completion
- Jul 2019 (estimated)
- First posted
- 13 Jul 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Healthy Controls | Experimental | Drug: Ursolic acidHealthy subjects will assigned to ursolic acid taken orally as a single dose of 40 mg, 80 mg, and 120 mg |
| PSC Single Dose | Experimental | Drug: Ursolic acidPSC subjects will assigned to ursolic acid taken orally as a single dose of 40 mg, 80 mg, and 120 mg |
| PSC Multiple Dose | Experimental | Drug: Ursolic acidPSC 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 |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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
Key exclusion criteria (7 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Ursolic acidAlso: urson, prunol, malol, 3-beta-3-hydroxy-urs-12-ene-28-oic-acidUrsolic acid (UA) is a natural triterpenoid carboxylic acid, which has been studied for its anti-proliferative and anti-inflammatory activities. | Drug | Healthy Controls, PSC Multiple Dose, PSC Single Dose |
Primary outcome
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]
Time frame: 24 hours
Number of serious adverse events or Grade 3-4 biochemical abnormalities
10 secondary outcomes
maximum plasma concentration (C¬max)
Time frame: 24 hours
half-life (t1/2),
Time frame: 24 hours
volume of distribution (Vd)
Time frame: 24 hours
clearance
Time frame: 24 hours
Area under the concentration-time curve (AUC)
Time frame: 24 hours
Alanine aminotransferase (ALT)
Time frame: 24 weeks
Total bilirubin
Time frame: 24 weks
C-reactive Protein (CRP)
Time frame: 24 weks
Mayo Risk Score (MRS)
Time frame: 24 weks
Biochemical response
Time frame: 24 weeks
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Jul 2017.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Christopher Bowlus, MD principal investigator
University of California, Davis
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Ursolic acid in people with Primary Sclerosing Cholangitis, run by University of California, Davis at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 25 Jul 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] (time frame: 24 hours). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Jul 2017.