Join a Current Trial

National Institutes of Health PSC Trials

The National Institutes of Health (NIH) offers a web site of clinical trials specific to PSC. You can visit the site by clicking here.

• http://www.clinicaltrials.gov/ct2/results?term=primary+sclerosing+cholangitis

At this time the following research trials are recruiting participants who have been diagnosed with PSC. These trials may or may not be related to the NIH trials.

New Clinical Study for PSC at Yale University (CT area)  

We are writing to inform you of a new clinical study at Yale University. It is entitled "Combination therapy with All-trans Retinoic Acid (ATRA) and Ursodeoxycholic acid (UDCA, also known as Urso or Actigall) in Primary Sclerosing Cholangitis (PSC): A Human Pilot Study".

The purpose of this research study is to determine whether the combination of UDCA and ATRA will improve laboratory tests of liver and bile duct inflammation in patients with PSC. Patients with PSC often have ongoing inflammation and fibrosis (scars) along the length of their bile ducts, and eventually this involves the liver itself which can lead to cirrhosis, infections (cholangitis), bile duct cancer and death. Although many patients are treated with UDCA and have improvement in liver tests and relief of symptoms, no medical treatment to date has produced long-term improvement of inflammation or survival. There is no Food and Drug Administration (FDA) approved medication for PSC, and therefore there is a great need to develop new regimens which can decrease liver and bile duct disease.

Recent work by our research group at Yale University School of Medicine has shown that the combination of UDCA and ATRA produced a significant improvement in liver scars and inflammation in animals with bile duct disease similar to that seen in PSC. This improvement included a lowering in the levels of bile acids, which are harmful to the liver, and a lowering of inflammation in the liver tissue of these animals. The benefits seen in this study were greater in animals receiving the combination of UDCA and ATRA compared to animals who received either medicine alone.

ATRA is related to vitamin A, and has been used for many years as a topical medication in the treatment of skin conditions such as acne and psoriasis.  It has also been used for nearly 20 years as an oral medicine, in the treatment of a form of blood cancer (acute promyelocytic leukemia) where it is well tolerated. ATRA has not yet been used in the care of patients with liver or bile duct disease.

Based on the benefits observed by treatment with ATRA and UDCA in our studies, we are now studying this combination in patients with PSC and believe that it may be an effective regimen for our patients. We will check blood tests of the liver and bile ducts before, during, and after the treatment period (3 months) to look for improvement in liver tests as a result of the drug combination. This study has been registered in the online database ClinicalTrials.gov (Study NCT 01456468).

We are currently enrolling patients with a diagnosis of PSC who have persistent elevation of alkaline phosphatase blood levels despite being on daily UDCA for at least six months. If you or someone you know is interested in participating, please contact us so that we can provide further information and arrange for a screening clinic visit at Yale. Please contact David N. Assis, MD at 203-785-5279 (phone) or 203-785-7273 (fax).

Thank you in advance for your attention.

Sincerely,
James L. Boyer, MD
David N. Assis, MD

Multicenter Trial of UDCA in Pediatric PSC Now Recruiting

Title: Ursodeoxycholic Acid Therapy in Pediatric Primary Sclerosing Cholangitis: A pilot Withdrawal/Reinstitution Trial (WUP PSC)

Primary sclerosing cholangitis (PSC), a devastating and insidiously progressive cholestatic liver disease, results from advancing inflammation, fibrosis and obliteration of the intra- and extrahepatic bile ducts, leading to cirrhosis and end-stage liver disease. PSC is an uncommon disorder (prevalence in the US of 8-14/100,000 with even lower prevalence in children). Although prognosis in children may be somewhat better, approximately one third of pediatric patients require transplantation by adulthood. Other than transplantation, there is to date no therapy conclusively proven to improve the long-term outcome. Ursodeoxycholic acid (UDCA) improves biochemical markers of liver disease, although in high doses does not clearly improve the long-term outcome in adults. Furthermore, a recent large adult trial of high-dose UDCA therapy suggested a higher incidence of serious adverse events and poor outcomes with UDCA treatment, leading many centers to discontinue UDCA therapy in adult patients. Childhood PSC is different from the adult disease including a stronger association with both autoimmune markers and histologic features and a trend to higher transaminases at diagnosis. Furthermore, in response to intermediate-dose UDCA therapy, there is a more striking and prompt improvement in biochemistries as compared to adults. In light of the prompt normalization of liver enzymes and the fact that UDCA is well tolerated in children, pediatric hepatologists are reluctant to generalize the adult UDCA study results to children and to stop UDCA therapy. This presents a significant dilemma: Should UDCA therapy be stopped in pediatric PSC patients to avoid a possible adverse influence on long-term prognosis at the risk of losing a possible beneficial effect on disease progression in children? Additional factors in children with PSC/autoimmune hepatitis (AIH) overlap are the long-term adverse effects of corticosteroids and azathioprine use. If UDCA therapy is effective as monotherapy, these complications may be avoided. Therefore, we are conducting a preliminary UDCA withdrawal and reinstitution trial sponsored by the FDA Office of Orphan Product Development in pediatric PSC patients to collect data to support the design of a larger, longer-term randomized, placebo-controlled trial of UDCA therapy in childhood PSC. This pilot study, which utilizes the infrastructure and participating centers of the STOPSC (Studies of Primary Sclerosing Cholangitis) consortium, will test the following hypotheses: 1) UDCA therapy yields a rapid biochemical response in children with PSC, thus withdrawal would lead to increased biochemical evidence of disease. 2) UDCA therapy suppresses liver and biliary inflammation in children with PSC, thus withdrawal of therapy would result in a burst of inflammatory activity and an increase in serum cytokine biomarkers, 3) Biochemical control of childhood PSC with histologic features of AIH is dependent upon treatment with immunosuppression in addition to UDCA, therefore childhood PSC without histologic features of AIH will worsen significantly with UDCA withdrawal compared to PSC with histological features of AIH.

More information on this study, including a list of participating centers and contact information, may be found at ClinicalTrials.gov:
http://www.clinicaltrials.gov/ct2/show/NCT01088607

For now, participants must live near a participating center.

Pilot Study of Fenofibrate for PSC 

The University of Miami (UM) and the University of Florida (UF) in Gainesville are seeking volunteers with confirmed diagnosis of PSC, age 18 and older, for participation in a clinical trial using a medication called fenofibrate. The study will investigate whether fenofibrate can improve liver tests and quality of life in patients with PSC. To be eligible, subjects must have elevated serum alkaline phosphatase.

As part of the study, subjects will take a medication daily for 6 months; this will be provided by the study. In addition, subjects will fill out a questionnaire, and blood tests will be performed at different time points. Available at the UM only, a fibroscan test will be performed at entry and end of study. Fibroscan is a non-invasive test, similar to an ultrasound, which estimates the stiffness/amount of scarring in the liver.

If you are interested in participating, or would like to receive more information, please contact Dimitri Duvilaire at 305-243-6939 or e-mail us at dduvilaire@med.miami.edu.

Noninvasive Assessment of Disease Progression in Primary Sclerosing Cholangitis

Dr. Everson and his colleagues at the University of Colorado Denver have pioneered the development of noninvasive tests to assess liver function as a way to identify the patients with more severe disease or patients whose disease is progressing. The tests have previously been studied primarily in patients with chronic hepatitis C. The main test involves oral and intravenous administration of naturally-occurring compounds, cholates, that are labeled with stable (not radioactive) isotopes (13C or 2H). Five blood samples are obtained over 90 minutes after the administration of cholates and serum analyzed for the concentrations of cholates. Hepatic blood flow, portal blood flow, and portal systemic shunt are estimated from the data. In patients with PSC the fibrosis accumulating in the liver causes portal hypertension, splenic enlargement, and varices. Changes in the portal circulation likely occur very early in the course of PSC and can be quantified by the cholate test. For this reason, the goal of the research is to study the cholate test in patients with PSC to determine if cholate testing can identify the patients with more severe disease and track disease progression. Participants in the research will be studied twice within one month (baseline) to define reproducibility of the test and then studied once more after one year to define the rate of disease progression. This research could provide a basis for considering noninvasive testing in the assessment of disease severity and tracking disease progression in patients with PSC.

If you think you might like to participate in this research study, please call Halley Isberg at 303 724-1862 or email her at Halley.isberg@ucdenver.edu.

Share your story to help us find the path of resilience!

Take the survey here! If you are a patient with cholestatic liver disease (PSC/PBC) or an inflammatory bowel disease, take this opportunity to be heard regarding the impact of your illness on the story of your life, how you think and feel, and your ability to be resilient! You may also earn a $50 gift certificate as a thank you. Philip Burke, who is conducting the study, is a PSCer.

The study is part of an important new research project being conducted by the Burke Narrative Studies Lab at Southern Illinois University at Carbondale. We are examining the definition and nature of resilience, its relationship to your physical and psychological health, and how you make sense of your illness in the broader story of your life as one element of resilience. Our goal is to identify what you and your healthcare providers can do to improve the quality of your life.

You can take the survey now online. Your participation may help find ways for people with chronic illness learn to be resilient. For individuals with PSC or PBC, you will also have the opportunity to take part in an interview about the story of your life and the role your illness plays in that story. For every 100 completed surveys, we will have a drawing for a $50 gift certificate. All you need to do is complete the survey.

If you want to take the survey but don’t feel comfortable completing the survey online, just give us a call at (618) 453-3407 and the team will set it up for you.

PROGRESS (PSC Resource Of Genetic Risk, Environment and Synergy Studies)

The Mayo Clinic is conducting a trial that is looking for participants who have PSC. The research website lists goals and participation requirements; click here for more information.

• http://mayoresearch.mayo.edu/mayo/research/
  lazaridis_lab/genomics_of_psc.cfm

The study asks for a small blood sample, and asks participants to fill out a questionnaire, all to examine genetic and environmental factors relating to PSC.

PSC Study at University of California/Davis

Dr. Eric Gershwin and Christopher Bowlus of the University of California are beginning a new study for PSC and PBC patients: Prevalence And Clinical Utility Of pANCA, ASCA, ANTI-OMPC, AND ANTI-CBIR1 In Patients With Primary Sclerosing Cholangitis.

To participate, subjects must be 18 years or older, have a diagnosis of PSC and not have had a transplant. They must provide a release of medical information along with a colonoscopy report and MRI or ERC documenting their PSC. Participation also requires a blood sample to be shipped to the researchers. The team has other studies that require fresh blood for immunologic study. Any patients in Northern California that would like to participate can contact Mia Minoletti at

• mia.minoletti@ucdmc.ucdavis.edugenomics_of_psc.cfm

• Call 916-703-5501 to arrange for an appointment at the center:
  University of California, Davis Medical Center
  TICON I Building
  2000 Stockton Blvd. Suite 100
  Sacramento, CA 95817

The university study does not have funding for collecting blood at other locations. The participant must be able to travel to Sacramento, unless the patient's doctor is interested in coordinating the patient's blood donation with Dr. Bowlus.

Different T-cells have specialized receptors to match specific antigens. Dr. Bowlus and Dr. Gershwin will study T-cells in PSC (and PBC) patients to determine if their blood displays a high concentration of T-cells with the same receptors. The goal of the study is to explore and identify a correlation, if any, between certain types of T-cells and PBC and PSC.

This is particularly important research. If the doctors identify a specific type of T-cell that is especially concentrated in PSC patients, we will be one big step closer to finding the cause of and perhaps the cure for PSC.

PSC in Twins

Genetically identical twin pairs in which one or both siblings have PSC are an enormous resource to determine the environmental factors contributing to the disease. Researchers at the Division of Rheumatology at UC Davis are searching for patients with PSC that have a twin, whether identical or fraternal. Dr. Carlo Selmi is leading a study on these issues and is interested in such twins whether they both have PSC or not and whether they are identical or not. The search for twins is ongoing throughout the world, if you know of anybody who is a patient with PSC and has a twin, please contact us using the email below. The study will only include a blood draw and a simple questionnaire for both twins.

• cfselmi@ucdavis.edu