Immune Modulation by Parenteral Fish Oil in Patients With Crohn's Disease
Condition: Crohn Disease
MeSH terms: Crohn Disease
Study type: Interventional
Phase: Phase 4

Summary: 
      To evaluate the effects of infusion of a Fish oil-based lipid emulsion on TNF-α production
      and other relevant immune functions. A soybean oil emulsion, rich in the omega-6
      polyunsaturated fatty acid linoleic acid, will serve as control.
    

Detailed description: 
      Rationale: Fish oil (FO), rich in omega-3 polyunsaturated fatty acids, exerts a range of
      anti-inflammatory actions that render it a potential therapeutic agent to treat Crohn's
      disease, a chronic inflammatory disease that primarily affects the bowel. Recent evidence
      suggests that a lack of effect in previous studies might be due to the fact that genetic
      background was not taken into account. For instance, a study in healthy subjects showed that
      production of the pro-inflammatory cytokine Tumor Necrosis Factor-alpha (TNF-α) following FO
      supplementation decreased in individuals within the highest tertile of pre-supplementational
      TNF-α production, remained unaltered in the middle tertile, and increased in the lowest
      tertile of pre-supplementational TNF-α production. TNF-α plays a pivotal role in the
      pathogenesis of Crohn's disease, hence the treatment with anti-TNF-α agents. Based on these
      notions, and because FO supplementation via the enteral route is strongly dose limited due to
      fat-induced side effects such as diarrhea, we hypothesize that parenteral FO supplementation
      might be beneficial in those patients with Crohn's disease with a high inherent TNF-α
      production.

      Study design: Single center, randomized, single blinded, lipid-controlled, cross-over pilot
      trial.

      Study population: Adult patients with Crohn's disease with previous bowel surgery, currently
      in remission (without the need for immunosuppressive drugs) and with a high inherent TNF-α
      production.

      Intervention: First, patients with a high inherent TNF-α will be identified by assessment of
      TNF-α production in a group 100 patients who meet in- and exclusion criteria. Patients within
      the highest tertile will be classified as high producers. Next, 5 patients within the highest
      tertile will be randomized to receive intravenous administration of 20% (w/v) lipid-control
      (Intralipid®), and, after crossing over, 10% (w/v) fish oil emulsion (Omegaven®), or
      vice-versa for 1 hour on three consecutive days at a dose of 0.2 g/kg bodyweight /hr. Study
      parameters will be assessed in blood drawn prior to the first infusion (T=0) and 1 (T=4) and
      8 days (T=11) after the third infusion. Between the two treatment arms, there will be a
      wash-out interval of at least 2-3 weeks.

      Main study parameters/endpoints: Early (T=day 4) and late (T=day 11) effects of infusions on
      TNF-α production by whole blood cultures. Secondary outcomes: effect on leukocyte counts,
      leukocyte functions and on (anti-)oxidant status, the occurrence of oxidative damage and
      analysis of specific Single Nucleotide Polymorphisms (SNPs) related to TNF-α production.
    

Intervention name(s): Omegaven 10%; Intralipid 20%
Intervention type(s): Drug; Drug
Intervention description(s): intravenous administration 10% (w/v) fish oil emulsion (Omegaven) for 1 hour on three consecutive days at a dose of 0.2 g/kg bodyweight/hr.; intravenous administration of 20% (w/v) lipid-control (Intralipid®), for 1 hour on three consecutive days at a dose of 0.2 g/kg bodyweight/hr.
Other intervention name(s): fish oil; N-3 polyunsaturated fatty acids atty acids; soybean oil; N-6 polyunsaturated fatty acids atty acids
Intervention MeSH terms: Soybean oil, phospholipid emulsion
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Single (Outcomes Assessor)
Primary purpose: Treatment