A Prospective, Randomized, Controlled, Double-blind, Crossover-Design, Mono-center, Phase IV Study Comparing the Effect of Omegaven in Combination With Clinoleic or Lipoplus or SMOFlipid in Home Parenteral Nutrition Patients
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 发起方
- 入组人数
- 24
- 试验地点
- 1
- 主要终点
- Change from baseline lipid emulsion production of IL-1-beta after in vitro stimulation of whole blood by lipopolysacharide at 4 weeks of Omegaven lipid emulsion addition
研究概览
简要总结
The aim of this study was to evaluate the safety and tolerance of ClinOleic or Lipoplus or SMOFlipid lipid emulsions. After 6 weeks of each lipid emulsion, Omegaven (fish oil) was added for a further 4 weeks. The safety and tolerance was evaluated after each lipid emulsion cycle by biochemistry, hematology and coagulation variables, vital signs and adverse events. We also analysed fatty acid profiles in plasma or erythrocyte phospholipids, antioxidant enzyme activities, lipid peroxidation products, plasma lipids and pro-inflammatory cytokine production after in vitro stimulation of whole blood by lipopolysacharide in HPN patients. The non-interventional group of healthy controls was included for comparison.
详细描述
Intravenous lipid emulsions (LEs) are an indispensable part of home parenteral nutrition (HPN). All commercially obtainable LEs are applicable for HPN in providing a source of energy and essential fatty acids. The originally used soyabean oil-based LE (Intralipid) have been suspected of being associated with a higher risk of pro-inflammatory lipid-mediator production due to their high content of n-6 polyunsaturated fatty acids. The more modern mixes of soyabean oil, and/or olive oil, and/or fish oil LEs with beneficial responses compared with Intralipid are available. Given that there are no clear clinical recommendations for LE application in HPN, we performed this cross-over design, phase 4 study comparing ClinOleic, Lipoplus or SMOFlipid in chronic intestinal failure patients with additional escalation of fish oil using Omegaven.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 85 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Home parenteral nutrition patients in need of parenteral nutrition administration > 4 days/week
- •Parenteral duration expectancy > 8 months
- •Stable clinical condition without any complications in the past 2 months
- •Written consent from the subject
排除标准
- •Known hypersensitivity to any of the active substances or excipients
- •Unstable conditions
- •Active cancer or its treatment
- •Established immunodeficiency
- •Advanced organ dysfunction from chronic disease
研究组 & 干预措施
1 Home Parenteral Nutrition, Cross-over
Random Cycle Sequence - Cycle 1: Clinoleic (baseline), 50g/per day, 42 days Clinoleic + Omegaven, 40g + 10g/per day, 28 days. Cycle 2: Lipoplus (baseline), 50g/per day, 42 days Lipoplus + Omegaven, 40g + 10g/per day, 28 days. Cycle 3: SMOFlipid (baseline), 50g/per day, 42 days SMOFlipid + Omegaven, 40g + 10g/per day, 28 days.
干预措施: ClinOleic (baseline) (Drug)
1 Home Parenteral Nutrition, Cross-over
Random Cycle Sequence - Cycle 1: Clinoleic (baseline), 50g/per day, 42 days Clinoleic + Omegaven, 40g + 10g/per day, 28 days. Cycle 2: Lipoplus (baseline), 50g/per day, 42 days Lipoplus + Omegaven, 40g + 10g/per day, 28 days. Cycle 3: SMOFlipid (baseline), 50g/per day, 42 days SMOFlipid + Omegaven, 40g + 10g/per day, 28 days.
干预措施: ClinOleic + Omegaven (Drug)
1 Home Parenteral Nutrition, Cross-over
Random Cycle Sequence - Cycle 1: Clinoleic (baseline), 50g/per day, 42 days Clinoleic + Omegaven, 40g + 10g/per day, 28 days. Cycle 2: Lipoplus (baseline), 50g/per day, 42 days Lipoplus + Omegaven, 40g + 10g/per day, 28 days. Cycle 3: SMOFlipid (baseline), 50g/per day, 42 days SMOFlipid + Omegaven, 40g + 10g/per day, 28 days.
干预措施: Lipoplus (baseline) (Drug)
1 Home Parenteral Nutrition, Cross-over
Random Cycle Sequence - Cycle 1: Clinoleic (baseline), 50g/per day, 42 days Clinoleic + Omegaven, 40g + 10g/per day, 28 days. Cycle 2: Lipoplus (baseline), 50g/per day, 42 days Lipoplus + Omegaven, 40g + 10g/per day, 28 days. Cycle 3: SMOFlipid (baseline), 50g/per day, 42 days SMOFlipid + Omegaven, 40g + 10g/per day, 28 days.
干预措施: Lipoplus + Omegaven (Drug)
1 Home Parenteral Nutrition, Cross-over
Random Cycle Sequence - Cycle 1: Clinoleic (baseline), 50g/per day, 42 days Clinoleic + Omegaven, 40g + 10g/per day, 28 days. Cycle 2: Lipoplus (baseline), 50g/per day, 42 days Lipoplus + Omegaven, 40g + 10g/per day, 28 days. Cycle 3: SMOFlipid (baseline), 50g/per day, 42 days SMOFlipid + Omegaven, 40g + 10g/per day, 28 days.
干预措施: SMOFlipid (baseline) (Drug)
1 Home Parenteral Nutrition, Cross-over
Random Cycle Sequence - Cycle 1: Clinoleic (baseline), 50g/per day, 42 days Clinoleic + Omegaven, 40g + 10g/per day, 28 days. Cycle 2: Lipoplus (baseline), 50g/per day, 42 days Lipoplus + Omegaven, 40g + 10g/per day, 28 days. Cycle 3: SMOFlipid (baseline), 50g/per day, 42 days SMOFlipid + Omegaven, 40g + 10g/per day, 28 days.
干预措施: SMOFlipid + Omegaven (Drug)
2 Home Parenteral Nutrition, Cross-over
Random Cycle Sequence - Cycle 1: Clinoleic (baseline), 50g/per day, 42 days Clinoleic + Omegaven, 40g + 10g/per day, 28 days. Cycle 2: Lipoplus (baseline), 50g/per day, 42 days Lipoplus + Omegaven, 40g + 10g/per day, 28 days. Cycle 3: SMOFlipid (baseline), 50g/per day, 42 days SMOFlipid + Omegaven, 40g + 10g/per day, 28 days.
干预措施: ClinOleic (baseline) (Drug)
2 Home Parenteral Nutrition, Cross-over
Random Cycle Sequence - Cycle 1: Clinoleic (baseline), 50g/per day, 42 days Clinoleic + Omegaven, 40g + 10g/per day, 28 days. Cycle 2: Lipoplus (baseline), 50g/per day, 42 days Lipoplus + Omegaven, 40g + 10g/per day, 28 days. Cycle 3: SMOFlipid (baseline), 50g/per day, 42 days SMOFlipid + Omegaven, 40g + 10g/per day, 28 days.
干预措施: ClinOleic + Omegaven (Drug)
2 Home Parenteral Nutrition, Cross-over
Random Cycle Sequence - Cycle 1: Clinoleic (baseline), 50g/per day, 42 days Clinoleic + Omegaven, 40g + 10g/per day, 28 days. Cycle 2: Lipoplus (baseline), 50g/per day, 42 days Lipoplus + Omegaven, 40g + 10g/per day, 28 days. Cycle 3: SMOFlipid (baseline), 50g/per day, 42 days SMOFlipid + Omegaven, 40g + 10g/per day, 28 days.
干预措施: Lipoplus (baseline) (Drug)
2 Home Parenteral Nutrition, Cross-over
Random Cycle Sequence - Cycle 1: Clinoleic (baseline), 50g/per day, 42 days Clinoleic + Omegaven, 40g + 10g/per day, 28 days. Cycle 2: Lipoplus (baseline), 50g/per day, 42 days Lipoplus + Omegaven, 40g + 10g/per day, 28 days. Cycle 3: SMOFlipid (baseline), 50g/per day, 42 days SMOFlipid + Omegaven, 40g + 10g/per day, 28 days.
干预措施: Lipoplus + Omegaven (Drug)
2 Home Parenteral Nutrition, Cross-over
Random Cycle Sequence - Cycle 1: Clinoleic (baseline), 50g/per day, 42 days Clinoleic + Omegaven, 40g + 10g/per day, 28 days. Cycle 2: Lipoplus (baseline), 50g/per day, 42 days Lipoplus + Omegaven, 40g + 10g/per day, 28 days. Cycle 3: SMOFlipid (baseline), 50g/per day, 42 days SMOFlipid + Omegaven, 40g + 10g/per day, 28 days.
干预措施: SMOFlipid (baseline) (Drug)
2 Home Parenteral Nutrition, Cross-over
Random Cycle Sequence - Cycle 1: Clinoleic (baseline), 50g/per day, 42 days Clinoleic + Omegaven, 40g + 10g/per day, 28 days. Cycle 2: Lipoplus (baseline), 50g/per day, 42 days Lipoplus + Omegaven, 40g + 10g/per day, 28 days. Cycle 3: SMOFlipid (baseline), 50g/per day, 42 days SMOFlipid + Omegaven, 40g + 10g/per day, 28 days.
干预措施: SMOFlipid + Omegaven (Drug)
结局指标
主要结局
Change from baseline lipid emulsion production of IL-1-beta after in vitro stimulation of whole blood by lipopolysacharide at 4 weeks of Omegaven lipid emulsion addition
时间窗: day 42, day 70
The whole blood culture supernatant concentration of IL-1-beta (ng/L)
Change from baseline lipid emulsion production of IL-6 after in vitro stimulation of whole blood by lipopolysacharide at 4 weeks of Omegaven lipid emulsion addition
时间窗: day 42, day 70
The whole blood culture supernatant concentration of IL-6 (ng/L)
Change from baseline lipid emulsion production of TNF-alpha after in vitro stimulation of whole blood by lipopolysacharide at 4 weeks of Omegaven lipid emulsion addition
时间窗: day 42, day 70
The whole blood culture supernatant concentration of TNF-alpha (ng/L)
Change from baseline lipid emulsion production of IL-8 after in vitro stimulation of whole blood by lipopolysacharide at 4 weeks of Omegaven lipid emulsion addition
时间窗: day 42, day 70
The whole blood culture supernatant concentration of IL-8 (ng/L)
次要结局
- Change from baseline lipid emulsion plasma concentration of fibrothelial growth factor 19 at 4 weeks of Omegaven lipid emulsion addition(day 42, day 70)
- Change from baseline lipid emulsion erythrocyte catalase activity at 4 weeks of Omegaven lipid emulsion addition(day 42, day 70)
- Alteration of liver function(week 6, week 10, week 16, week 20, week 26, week 30)
- Change from baseline lipid emulsion plasma concentration of LDL cholesterol at 4 weeks of Omegaven lipid emulsion addition(day 42, day 70)
- Change from baseline lipid emulsion plasma concentration of TNF-alpha at 4 weeks of Omegaven lipid emulsion addition(day 42, day 70)
- Change from baseline lipid emulsion plasma concentration of IL-1-beta at 4 weeks of Omegaven lipid emulsion addition(day 42, day 70)
- Change from baseline lipid emulsion plasma concentration of total cholesterol at 4 weeks of Omegaven lipid emulsion addition(day 42, day 70)
- Change from baseline lipid emulsion plasma phospholipid fatty acid profile at 4 weeks of Omegaven lipid emulsion addition(day 42, day 70)
- Change from baseline lipid emulsion erythrocyte phospholipid fatty acid profile at 4 weeks of Omegaven lipid emulsion addition(day 42, day 70)
- Change from baseline lipid emulsion erythrocyte glutathione reductase activity at 4 weeks of Omegaven lipid emulsion addition(day 42, day 70)
- Change from baseline lipid emulsion plasma concentration of IL-6 at 4 weeks of Omegaven lipid emulsion addition(day 42, day 70)
- Change from baseline lipid emulsion plasma concentration ratio of oxidized LDL/LDL cholesterol at 4 weeks of Omegaven lipid emulsion addition(day 42, day 70)
- Change from baseline lipid emulsion erythrocyte superoxide dismutase activity at 4 weeks of Omegaven lipid emulsion addition(day 42, day 70)
- Change from baseline lipid emulsion plasma paraoxonase 1 activity at 4 weeks of Omegaven lipid emulsion addition(day 42, day 70)
- Change from baseline lipid emulsion plasma concentration of IL-8 at 4 weeks of Omegaven lipid emulsion addition(day 42, day 70)
- Change from baseline lipid emulsion plasma concentration of triglycerides at 4 weeks of Omegaven lipid emulsion addition(day 42, day 70)
- Change from baseline lipid emulsion plasma concentration of HDL cholesterol at 4 weeks of Omegaven lipid emulsion addition(day 42, day 70)
- Change from baseline lipid emulsion erythrocyte glutathione peroxidase activity at 4 weeks of Omegaven lipid emulsion addition(day 42, day 70)
- Septic complications(week 6, week 10, week 16, week 20, week 26, week 30)
研究者
Frantisek Novak
Chief physician
General University Hospital, Prague