NCT01456468

Brief Summary

The purpose of this research study is to determine whether the combination of UDCA and ATRA taken for 3 months will improve laboratory tests of liver and bile duct inflammation in patients with Primary Sclerosing Cholangitis (PSC). Our hypothesis is that a combination of these medications will improve the liver inflammatory tests in these patients, specifically a reduction in alkaline phosphatase (AP) by at least 30%.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
19

participants targeted

Target at P25-P50 for phase_1

Timeline
Completed

Started Oct 2011

Longer than P75 for phase_1

Geographic Reach
1 country

2 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

October 1, 2011

Completed
13 days until next milestone

First Submitted

Initial submission to the registry

October 14, 2011

Completed
6 days until next milestone

First Posted

Study publicly available on registry

October 20, 2011

Completed
2.6 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

June 1, 2014

Completed
1.5 years until next milestone

Study Completion

Last participant's last visit for all outcomes

December 1, 2015

Completed
Last Updated

July 14, 2016

Status Verified

July 1, 2016

Enrollment Period

2.7 years

First QC Date

October 14, 2011

Last Update Submit

July 12, 2016

Conditions

Cholangitis, Sclerosing

Keywords

Cholangitis, SclerosingTretinoinUrsodeoxycholic Acid

Outcome Measures

Primary Outcomes (1)

  • Improvement in serum alkaline phosphatase levels

    The primary outcome measure is a 30% improvement in serum alkaline phosphatase in subjects, comparing pre- and post-treatment values for each individual.

    Baseline and after 3 months of treatment.

Study Arms (1)

UDCA + ATRA

EXPERIMENTAL

This is a single-arm study. All subjects will take UDCA and ATRA.

Drug: Oral all-trans retinoic acid (ATRA)

Interventions

Oral all-trans retinoic acid (ATRA)DRUG

The subjects will continue to take their current dose of UDCA (15 mg/kg/day), as per ongoing clinical care, and need to be on a stable dose of UDCA for at least six months prior to enrollment. The specific intervention is the addition of daily oral ATRA (45 mg/m\^2) divided into 2 doses. To increase adherence to the dosing regimen, the drug will be compounded by the Research Pharmacies of Yale and Mayo into 2 formulations (30 mg and 40 mg capsules), and an Investigational New Drug (IND) permit was obtained for this process.

Also known as: The medication is all-trans retinoic acid (ATRA).
UDCA + ATRA

Eligibility Criteria

Age18 Years - 80 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Diagnosis of PSC for at least 6 months, made by clinical evaluation in addition to one of the following: a prior endoscopic retrograde cholangiography (ERC), magnetic resonance cholangiography (MRC, also termed MRI/MRCP) or liver biopsy.
  • Progressing disease or stable disease with persistent elevation in AP despite treatment with UDCA (15 mg/kg/day) for at least 6 months.
  • Measures of progressing disease:
  • Cholangitis within the past 12 months.
  • Presence or progression of biliary abnormalities on MRI/MRC.
  • Elevated liver tests (alkaline phosphatase, bilirubin, aspartate aminotransferase \[AST\], alanine aminotransferase \[ALT\]).
  • Age between 18 and 80.

You may not qualify if:

  • Pregnancy or planned pregnancy during study period and within 6 months of study completion.
  • Common Terminology Criteria for Adverse Events (CTCAE) grade 3 or higher cardiac disease, hyperlipidemia, hypertriglyceridemia, hepatic injury, or adverse event related to administration of UDCA or ATRA.
  • Prior intolerance to UDCA or ATRA (or related oral vitamin A compounds).
  • Evidence of decompensated cirrhosis within the past 6 months (i.e. variceal bleeding, uncontrolled ascites, hepatic encephalopathy, jaundice).
  • Estimated need for liver transplantation within 1 year.
  • Any evidence of hepatocellular carcinoma, cholangiocarcinoma, or other malignancy.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (2)

Yale University School of Medicine - 333 Cedar St - 1080 LMP

New Haven, Connecticut, 06520, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Related Publications (1)

  • He H, Mennone A, Boyer JL, Cai SY. Combination of retinoic acid and ursodeoxycholic acid attenuates liver injury in bile duct-ligated rats and human hepatic cells. Hepatology. 2011 Feb;53(2):548-57. doi: 10.1002/hep.24047. Epub 2010 Dec 10.

    PMID: 21274875BACKGROUND

MeSH Terms

Conditions

Cholangitis, Sclerosing

Interventions

Tretinoin

Condition Hierarchy (Ancestors)

CholangitisBile Duct DiseasesBiliary Tract DiseasesDigestive System Diseases

Intervention Hierarchy (Ancestors)

Vitamin ARetinoidsCarotenoidsPolyenesAlkenesHydrocarbons, AcyclicHydrocarbonsOrganic ChemicalsCyclohexenesCyclohexanesCycloparaffinsHydrocarbons, AlicyclicHydrocarbons, CyclicTerpenesDiterpenesPigments, BiologicalBiological Factors

Study Officials

  • James L Boyer, MD

    Yale University

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Professor of Medicine

Study Record Dates

First Submitted

October 14, 2011

First Posted

October 20, 2011

Study Start

October 1, 2011

Primary Completion

June 1, 2014

Study Completion

December 1, 2015

Last Updated

July 14, 2016

Record last verified: 2016-07

Locations

US(2)