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Trial record 57 of 92 for:    Primary Sclerosing Cholangitis

Evaluation of DHA for the Treatment of PSC

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00325013
Recruitment Status : Completed
First Posted : May 11, 2006
Last Update Posted : March 11, 2015
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Information provided by (Responsible Party):
Steven Freedman, Beth Israel Deaconess Medical Center

Brief Summary:
The researches aim to study the effects of DHA (component of fish oil) on patients with Primary Sclerosing Cholangitis (PSC). Our hypothesis is that DHA might reverse the problems associated with PSC.

Condition or disease Intervention/treatment Phase
Primary Sclerosing Cholangitis Colitis Drug: Docosahexaenoic Acid (DHA) Phase 1

Detailed Description:

The etiology of Primary Sclerosing Cholangitis (PSC) is unknown. There are no proven effective therapies and no early markers of the disease to predict which patients with colitis may be at risk to develop PSC.

Our group has demonstrated an increased prevalence of CFTR alleles (the gene responsible for Cystic Fibrosis (CF)) in patients with PSC which was correlated with decreased CFTR function as measured by Nasal Potential Difference Testing. These data suggested that colitis in the setting of CFTR dysfunction may lead to bile duct inflammation and fibrosis. As proof of concept, we subsequently demonstrated in cftr-/- mice that (1) colitis leads to the development of bile duct injury and (2) this is prevented by correction of the CFTR related fatty acid defect with oral Docosahexaenoic Acid (DHA). Preliminary data in these mice indicates that low PPAR expression in the liver may predispose to inflammation. One mechanism by which DHA ameliorates the innate inflammatory response linked to CFTR dysfunction may be through an increase in PPAR expression.

Based on these data, we hypothesize that CFTR dysfunction may contribute to the pathogenesis of primary sclerosing cholangitis (PSC). Furthermore, correction of the fatty acid abnormality and changes in the innate immune response associated with CFTR dysfunction by oral administration of docosahexaenoic acid (DHA), an n-3 polyunsaturated fatty acid, might be an effective therapy for patients with PSC.

Immediate Objectives:

To evaluate the effect of DHA therapy on patients with PSC, examining:

Primary Outcome:

• serum alkaline phosphatase

Secondary Outcomes:

  • cholangiography
  • liver biochemistry (ALT, AST, gamma-glutamyl transferase, bilirubin, albumin, prothrombin time,)
  • fatty acid profile (docosahexaenoic acid, arachidonic acid)
  • serum/plasma liver fibrosis markers (hyaluronic acid, tumor necrosis factor-α, transforming growth factor-ß, type III procollagen peptide)
  • innate immune response (peripheral blood monocytes for assessment of cytokine secretion, lipoxins, and PPAR)
  • clinical data on signs and symptoms

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 10 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Evaluation of Docosahexaenoic Acid (DHA) for the Treatment of Primary Sclerosing Cholangitis (PSC)
Study Start Date : December 2005
Actual Primary Completion Date : May 2012
Actual Study Completion Date : May 2012

Arm Intervention/treatment
Experimental: II Drug: Docosahexaenoic Acid (DHA)
800mg twice a day for 1 year
Other Name: fish oil

Primary Outcome Measures :
  1. Primary outcome will be change in alkaline phosphatase. Outcome in alkaline phosphatase will be defined as:Highly positive: >50% reduction;Positive: >25% reduction; [ Time Frame: 1 years ]
  2. No Change: <25% reduction or <25% increase;Negative: >25% increase;Highly negative: >50% increase [ Time Frame: 1 years ]

Secondary Outcome Measures :
  1. Secondary outcomes will include changes in:cholangiography;liver biochemistry (ALT, AST, gamma-glutamyl transferase, bilirubin, albumin, prothrombin time);fatty acid profile (docosahexaenoic acid, arachidonic acid); [ Time Frame: 1 years ]
  2. serum/plasma liver fibrosis markers (hyaluronic acid, tumor necrosis factor-α, transforming growth factor-ß, type III procollagen peptide);peripheral blood monocyte PPAR (mRNA by RT-PCR, protein level by western blot, and activity by EMSA); [ Time Frame: 1 year ]
  3. peripheral blood monocyte cytokine secretion (IL-8) in response to Pseudomonas LPS, TNF, IL-10; lipoxin A4 secretion and lipoxygenase expression as well as docosatriene/resolvins;symptoms;safety measures of DHA (Adverse Event recordings) [ Time Frame: 1 year ]

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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

Patients must have a diagnosis of primary sclerosing cholangitis. The diagnosis will require a chronic cholestatic liver disease of at least 6 months' duration; a serum alkaline phosphatase level at least 1.5 times the upper limit of normal; cholangiographic findings of intrahepatic or extrahepatic biliary-duct obstruction, beading, or narrowing consistent with PSC; and a liver biopsy in the previous 12 months with compatible findings.

Exclusion Criteria:

Age less than18 years or more than 80 years. Subjects must have no evidence of secondary cholangitis or other liver disease (primary biliary cirrhosis, alcoholic liver disease, autoimmune hepatitis, and chronic viral hepatitis). Subjects will be excluded if there is a history of previous bile duct surgery, previous choledocholithiasis, recurrent ascending cholangitis, previous history of variceal hemorrhage, or cholangiocarcinoma. Subjects with PSC stage III (fibrosis) or IV (cirrhosis) based on the criteria of Ludwig et al. will be excluded.

Participants will be excluded if there are pregnant.

Subjects will also be excluded if treatment with corticosteroids, cyclosporine or methotrexate has occurred within the preceding 3 months, or there is an anticipated need for liver transplantation within 1 year. No fish oil supplements will otherwise be allowed. Patients on 5-aminosalicylate preparations or azathioprine will remain on these preparations for the duration of the trial. Treatment with ursodeoxycholic acid will not be an exclusion criteria. Patients on this therapy will be advised to continue the drug throughout the trial. Those not on ursodeoxycholic acid will not be allowed to start this drug since it is could affect the alkaline phosphatase levels and is not an accepted efficacious therapy. Subjects will not be excluded for refusal of follow-up MRCP at study completion. There will be no exclusion based on sex, race, and ethnic background.

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 identifier (NCT number): NCT00325013

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United States, Massachusetts
Beth Israel Deaconess Medical Center
Boston, Massachusetts, United States, 02215
United States, Minnesota
Mayo Clinic
Rochester, Minnesota, United States, 55905
Sponsors and Collaborators
Beth Israel Deaconess Medical Center
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
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Principal Investigator: Steve D Freedman, MD, PhD Beth Israel Deaconess Medical Center

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Responsible Party: Steven Freedman, MD PhD Professor of Medicine at Harvard School of Medicine, Beth Israel Deaconess Medical Center Identifier: NCT00325013     History of Changes
Other Study ID Numbers: 2005P-000259 (DK71851)
R03DK071851 ( U.S. NIH Grant/Contract )
First Posted: May 11, 2006    Key Record Dates
Last Update Posted: March 11, 2015
Last Verified: March 2015
Keywords provided by Steven Freedman, Beth Israel Deaconess Medical Center:
Primary Sclerosing Cholangitis
Docosahexaenoic Acid
Additional relevant MeSH terms:
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Cholangitis, Sclerosing
Digestive System Diseases
Bile Duct Diseases
Biliary Tract Diseases