Immune Modulation by Parenteral Fish Oil in Patients With Crohn's Disease

NCT ID: NCT02349594

Last Updated: 2015-11-10

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 6 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-01-31
• Study Completion Date: 2015-09-30

Brief 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.

Conditions

Crohn Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

treatment order A

Participants in this arm first receive 'Omegaven 10%' and after crossing over the 'Intralipid 20%'

Group Type: ACTIVE_COMPARATOR

Omegaven 10%

Intervention Type: DRUG

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.

Intralipid 20%

Intervention Type: DRUG

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.

treament order B

Participants in this arm first receive 'Intralipid 20%' and after crossing over the 'Omegaven 10%'

Group Type: ACTIVE_COMPARATOR

Omegaven 10%

Intervention Type: DRUG

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.

Intralipid 20%

Intervention Type: DRUG

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.

Interventions

Omegaven 10%

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.

Intervention Type: DRUG

Intralipid 20%

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.

Intervention Type: DRUG

Other Intervention Names

fish oil; N-3 polyunsaturated fatty acids atty acids; soybean oil; N-6 polyunsaturated fatty acids atty acids

Eligibility Criteria

Inclusion Criteria

• 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.

Exclusion Criteria

• Patients with other active inflammatory / immune mediated underlying diseases
• Smoking > 5 cigarettes a day
• Diet with >2 portions of fatty fish (tuna, salmon, mackerel, herring, and trout) a week
• History of metabolic disorder (especially diabetes or lipid disorders)
• Crohn's disease activity, including the presence of active fistulas
• On need for medical (other than 5-aminosalicylic acid preparations) or surgical treatment for Crohn's disease activity
• Use of non-steroidal anti-inflammatory drugs or aspirin
• C-reactive protein levels of >10 mg/l
• History of venous or arterial thrombosis
• Active malignancy
• Presence of severe pulmonary, cardiovascular, renal, liver, coagulation or hematological disease
• Pregnancy or lactation
• Age <18 yrs
• Allergy for one of the following components: fish, chicken, eggs or soy beans

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Radboud University Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

G. Wanten, MD, PhD

Role: STUDY_DIRECTOR

Radboud University Nijmegen Medical Center

F. Hoentjen, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Radboud University Nijmegen Medical Center

D de Jong, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Radboud University Nijmegen Medical Center

P. Calder, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

University Hospital Southampton NHS Foundation Trust

Locations

Radboud University Medical Center

Nijmegen, , Netherlands

Countries

Netherlands

Other Identifiers

2013-001212-30

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

GW/MB/42964

Identifier Type: -

Identifier Source: org_study_id