Modulation of Immune Function by Parenteral Fish Oil in Patients With Crohn's Disease and High Inherent Tumor Necrosis Factor-alpha Production: a Randomized, Single Blinded, Cross-over Study
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 6
- 试验地点
- 1
- 主要终点
- Change of TNF-α production in pg/ml
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- Single (Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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
研究组 & 干预措施
treatment order A
Participants in this arm first receive 'Omegaven 10%' and after crossing over the 'Intralipid 20%'
干预措施: Omegaven 10% (Drug)
treatment order A
Participants in this arm first receive 'Omegaven 10%' and after crossing over the 'Intralipid 20%'
干预措施: Intralipid 20% (Drug)
treament order B
Participants in this arm first receive 'Intralipid 20%' and after crossing over the 'Omegaven 10%'
干预措施: Omegaven 10% (Drug)
treament order B
Participants in this arm first receive 'Intralipid 20%' and after crossing over the 'Omegaven 10%'
干预措施: Intralipid 20% (Drug)
结局指标
主要结局
Change of TNF-α production in pg/ml
时间窗: day 0 and day 4
whole blood cultures are stimulated with 1 ng/ml lipopolysaccharide for 4 hours. TNF-alpha levels are measured in the supernatant with an enzyme-linked immunosorbent assay. Differences are compared by paired t-test or wilcoxon signed rank test.
次要结局
- short term change in leukocyte functions(day 0 and day 4)
- long term change in leukocyte functions(day 0 and day 11)
- change in Oxygen radical production by neutrophils(day 0 and day 11)
- short term effects on in cytokine production(day 0 and day 4)
- Long term effects on in cytokine production(day 0 and day 11)
- Composition of phospholipids in the cell membrane(day 0, day4 and day 11)
- Change of TNF-α production in pg/ml(day 0 and day 11)
- (anti-) Oxidant status and oxidative damage(day 0 and day 11)