Evaluation of DHA for the Treatment of PSC
Condition: Primary Sclerosing Cholangitis; Colitis
MeSH terms: Cholangitis; Cholangitis, Sclerosing
Study type: Interventional
Phase: Phase 1

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
    

Intervention name(s): Docosahexaenoic Acid (DHA)
Intervention type(s): Drug
Intervention description(s): 800mg twice a day for 1 year
Other intervention name(s): fish oil
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Primary Sclerosing Cholangitis; PSC; DHA; Docosahexaenoic Acid