Evaluation of DHA for the Treatment of PSC

NCT ID: NCT00325013

Last Updated: 2015-03-11

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 10 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2005-12-31
• Study Completion Date: 2012-05-31

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.

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

Conditions

Primary Sclerosing Cholangitis; Colitis

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

II

Group Type: EXPERIMENTAL

Docosahexaenoic Acid (DHA)

Intervention Type: DRUG

800mg twice a day for 1 year

Interventions

Docosahexaenoic Acid (DHA)

800mg twice a day for 1 year

Intervention Type: DRUG

Other Intervention Names

fish oil

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

NIH

Sponsor Role: collaborator

Beth Israel Deaconess Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Steven Freedman

MD PhD Professor of Medicine at Harvard School of Medicine

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Steve D Freedman, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Beth Israel Deaconess Medical Center

Locations

Beth Israel Deaconess Medical Center

Boston, Massachusetts, United States

Mayo Clinic

Rochester, Minnesota, United States

Countries

United States

Other Identifiers

R03DK071851

Identifier Type: NIH

Identifier Source: secondary_id

View Link

2005P-000259 (DK71851)

Identifier Type: -

Identifier Source: org_study_id