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Crossover Study on the Effect of Omegaven in Combination With Different Lipid Emulsions in Home Parenteral Nutrition

Phase 4
Completed
Conditions
Parenteral Nutrition
Interventions
Drug: Lipoplus (baseline)
Drug: Lipoplus + Omegaven
Drug: SMOFlipid (baseline)
Drug: SMOFlipid + Omegaven
Registration Number
NCT03149653
Lead Sponsor
General University Hospital, Prague
Brief Summary

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.

Detailed Description

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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
24
Inclusion Criteria
  • 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
Exclusion Criteria
  • 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

Study & Design

Study Type
INTERVENTIONAL
Study Design
CROSSOVER
Arm && Interventions
GroupInterventionDescription
1 Home Parenteral Nutrition, Cross-overClinOleic (baseline)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.
2 Home Parenteral Nutrition, Cross-overClinOleic + OmegavenRandom 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.
1 Home Parenteral Nutrition, Cross-overLipoplus (baseline)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.
1 Home Parenteral Nutrition, Cross-overSMOFlipid + OmegavenRandom 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.
2 Home Parenteral Nutrition, Cross-overClinOleic (baseline)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.
2 Home Parenteral Nutrition, Cross-overLipoplus (baseline)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.
2 Home Parenteral Nutrition, Cross-overSMOFlipid + OmegavenRandom 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.
1 Home Parenteral Nutrition, Cross-overClinOleic + OmegavenRandom 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.
2 Home Parenteral Nutrition, Cross-overSMOFlipid (baseline)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.
1 Home Parenteral Nutrition, Cross-overLipoplus + OmegavenRandom 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.
1 Home Parenteral Nutrition, Cross-overSMOFlipid (baseline)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.
2 Home Parenteral Nutrition, Cross-overLipoplus + OmegavenRandom 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.
Primary Outcome Measures
NameTimeMethod
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 additionday 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 additionday 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 additionday 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 additionday 42, day 70

The whole blood culture supernatant concentration of IL-8 (ng/L)

Secondary Outcome Measures
NameTimeMethod
Alteration of liver functionweek 6, week 10, week 16, week 20, week 26, week 30

Liver function tests

Change from baseline lipid emulsion erythrocyte catalase activity at 4 weeks of Omegaven lipid emulsion additionday 42, day 70

The erythrocyte activity of CAT (U/g Hb)

Change from baseline lipid emulsion plasma concentration of fibrothelial growth factor 19 at 4 weeks of Omegaven lipid emulsion additionday 42, day 70

The plasma concentration of fibrothelial growth factor 19 (ng/L)

Change from baseline lipid emulsion plasma concentration of TNF-alpha at 4 weeks of Omegaven lipid emulsion additionday 42, day 70

The plasma concentration of TNF-alpha (ng/L)

Change from baseline lipid emulsion plasma concentration of IL-1-beta at 4 weeks of Omegaven lipid emulsion additionday 42, day 70

The plasma concentration of IL-1-beta (ng/L)

Change from baseline lipid emulsion plasma concentration of total cholesterol at 4 weeks of Omegaven lipid emulsion additionday 42, day 70

The plasma concentration of total cholesterol (mmol/L)

Change from baseline lipid emulsion plasma concentration of LDL cholesterol at 4 weeks of Omegaven lipid emulsion additionday 42, day 70

The plasma concentration of LDL cholesterol (mmol/L)

Change from baseline lipid emulsion plasma phospholipid fatty acid profile at 4 weeks of Omegaven lipid emulsion additionday 42, day 70

The plasma phospholipid fatty acid profile (mol%)

Change from baseline lipid emulsion erythrocyte phospholipid fatty acid profile at 4 weeks of Omegaven lipid emulsion additionday 42, day 70

The erythrocyte phospholipid fatty acid profile (mol%)

Change from baseline lipid emulsion erythrocyte glutathione reductase activity at 4 weeks of Omegaven lipid emulsion additionday 42, day 70

The erythrocyte activity of GR (U/g Hb)

Change from baseline lipid emulsion plasma concentration of IL-6 at 4 weeks of Omegaven lipid emulsion additionday 42, day 70

The plasma concentration of IL-6 (ng/L)

Change from baseline lipid emulsion plasma concentration ratio of oxidized LDL/LDL cholesterol at 4 weeks of Omegaven lipid emulsion additionday 42, day 70

The plasma concentration ratio of oxidized LDL/LDL cholesterol (ox-LDL/LDL-C)

Change from baseline lipid emulsion erythrocyte superoxide dismutase activity at 4 weeks of Omegaven lipid emulsion additionday 42, day 70

The erythrocyte activity of SOD (U/g Hb)

Change from baseline lipid emulsion plasma paraoxonase 1 activity at 4 weeks of Omegaven lipid emulsion additionday 42, day 70

The plasma activity of PON1 (U/L)

Change from baseline lipid emulsion plasma concentration of IL-8 at 4 weeks of Omegaven lipid emulsion additionday 42, day 70

The plasma concentration of IL-8 (ng/L)

Change from baseline lipid emulsion plasma concentration of triglycerides at 4 weeks of Omegaven lipid emulsion additionday 42, day 70

The plasma concentration of triglycerides (mmol/L)

Change from baseline lipid emulsion plasma concentration of HDL cholesterol at 4 weeks of Omegaven lipid emulsion additionday 42, day 70

The plasma concentration of HDL cholesterol (mmol/L)

Change from baseline lipid emulsion erythrocyte glutathione peroxidase activity at 4 weeks of Omegaven lipid emulsion additionday 42, day 70

The erythrocyte activity of GPX (U/g Hb)

Septic complicationsweek 6, week 10, week 16, week 20, week 26, week 30

Catheter-related bloodstream infections

Trial Locations

Locations (1)

General University Hospital

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Prague, Czechia

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