An interventional study of n3-LCPUFA enriched Intravenous Lipid Emulsion in Very Low Birth Weight Infant and Bronchopulmonary Dysplasia, sponsored by University of Calgary. Status unknown at 1 site in Canada. Open to participants aged 1 Hour to 48 Hours. Per ClinicalTrials.gov, last updated 2022-11-07.
Sponsored by University of Calgary · Not applicable, Interventional, and Prevention
Despite many advances in neonatal care in the recent years, bronchopulmonary dysplasia (BPD) continues to be the major cause of chronic lung morbidity in infants. The pathogenesis of BPD is multifactorial; however, inflammation remains the central pathway for all risk factors. Omega-3 long chain polyunsaturated fatty acids (n3-LCPUFAs) from fish oil are known to down-regulate systemic inflammation and oxidative stress. Currently used soybean-based fatty acid emulsion (Intralipid) contains mainly n6-LCPUFA. Intralipid does not maintain the in-utero balanced LCPUFA accretion. Furthermore, Intralipid has been shown to increase free radical production and to be associated with BPD. A new fatty acid emulsion enriched with n3-LCPUFA (SMOFlipid) improves the fatty acid profile and reduces pro-inflammatory agents.
This project aims primarily to study whether SMOFlipid can lower the rate of BPD in preterm infants compared to Intralipid.
Intravenous lipid emulsions (IVLEs) is a core component of parenteral nutrition (PN) for providing calories and essential fatty acids. Until recently, Intralipid was the only available IVLE in North America. For a long time now, the use of Intralipid has been described to be associated with the development of BPD. Lack of sufficient lipid clearance in premature infants, augmented oxidative stress, deficiency of anti-inflammatory agents, and elevated pulmonary artery pressure have all shown to be potential causes for lung injury during the use of Intralipid.
Intralipid, made mainly of soybean oil, contains high amounts of n6-LCPUFA and low amounts of n3-LCPUFA. This results in prostaglandin synthesis favoring pro-inflammatory products and amplified oxidative stress. Current evidence indicates that well-balanced fatty acid supply is a crucial factor to reduce inflammation and oxidative stress. The concern about unbalanced n6:n3 ratio has led to the development of novel IVLEs, like SMOFlipid. SMOFlipid is composed of a mixture of soybean oil (30%), medium-chain triglycerides (MCT) (30%), olive oil (25%) and fish oil (15%). The combination of soybean oil and fish oil allows delivering balanced LCPUFA with n6:n3 ratio of 2.5:1 and provides sufficient amounts of the preformed n3-LCPUFA.
Interventions that improve n3-LCPUFA status have been shown to reduce pulmonary inflammation in animal models.
In humans, a study on extremely preterm infants has revealed a rapid decline in the n3-LCPUFA in the first week of life despite the use of Intralipid. Early restoration of an adequate ratio of LCPUFA to inhibit inflammation has gained interest in recent years. In an observational study by Skouroliakou et al., very low birth weight infants receiving SMOFlipid within 48 hours of birth and for at least 7 days had a lower incidence of BPD compared to the Intralipid control group. A recent systematic review and meta-analysis of 8 randomized control trials (7 compared SMOFlipid to Intralipid) was conducted to evaluate safety and efficacy of fish oil-enriched IVLEs in preterm infants. Infants who received fish oil-enriched IVLEs had significantly higher RBC membrane DHA and EPA. The meta-analysis showed no difference in all-cause mortality and overall complication rate in 238 infants receiving fish oil-enriched IVLEs. However, all the studies included in this meta-analysis were small. Furthermore, the studies focused mainly on laboratory findings, and did not aim to study effect on inflammation, oxidative stress or clinical outcomes. Studies from critically ill adults in intensive care units exhibited a reduction in the duration of hospitalization and ventilator days, a risk factor for lung injury, when using n3-LCPUFA enriched IVLEs.
339 studies on the registry are indexed under Bronchopulmonary Dysplasia; 80 are open to participants now.
This study's planned enrollment of 384 is above the median of 70 across 228 interventional studies indexed under Bronchopulmonary Dysplasia.
Browse Bronchopulmonary Dysplasia studies →University of Calgary is the lead sponsor of 686 studies on the registry; 189 are open to participants now.
Of its 10 completed or terminated interventional studies of FDA-regulated products, 2 (20%) have results posted.
Counted across the registry records on this site, refreshed daily.
Exclusion Criteria:
Conventional IVLE (Intralipid) from D0 at 1g/kg/day and increase by 1 g/kg daily till reaching 3 g/kg/day.
n3-LCPUFA enriched IVLE (SMOFlipid) from D0 at 1g/kg/day and increase by 1 g/kg daily till reaching 3 g/kg/day.
Other: n3-LCPUFA enriched Intravenous Lipid Emulsion
To start from D0 at 1g/kg/day and increase by 1 g/kg daily till reaching 3 g/kg/day.
Also known as: SMOFlipid
The incidence of Bronchopulmonary Disease
According to Child Health and Human Development with classification to mild, moderate and severe.
Time frame: 36 weeks corrected gestational age
Fatty acid profile
Determine serum fatty acids levels (μmol/L).
Time frame: First 3 weeks of life
Pro-inflammatory cytokine response
Compare pro-inflammatory cytokine levels (pg/mL)
Time frame: First 3 weeks of life
Lipid peroxidation measure 1
Malondialdehyde (MDA, μmol/L) in blood
Time frame: First 3 weeks of life
Lipid peroxidation measure 2
8-isoprostane levels (pg/mL) in blood
Time frame: First 3 weeks of life
Incidence of Cholestasis
Direct bilirubin more than 34 mmol/L
Time frame: Up to 36 weeks corrected gestational age or discharge
Weight gain velocity
Change in weight Z scores
Time frame: Up to 36 weeks corrected gestational age or discharge
Incidence of retinopathy of prematurity
Defined as stage 2 or higher according to the international classification or requiring treatment.
Time frame: Up to 36 weeks corrected gestational age or discharge
Incidence of moderate to severe neurodevelopmental disability
Defined by 1 or more of the following: moderate to severe motor impairment cerebral palsy (CP) or non-CP) with a GMFCS level ≥2, a BSID III cognitive score of \<70, severe visual impairment (bilateral blindness with vision \<20/200), or severe hearing impairment (permanent hearing loss that interferes with ability to understand or communicate with or without amplification).
Time frame: 18-22 months corrected gestational
Incidence of severe intraventricular hemorrhage (IVH)
Defined as grade 3 or higher
Time frame: Up to 36 weeks corrected gestational age or discharge
Plan to share: No
No publications or documents are linked to this record.
This study is status unknown, as verified in Nov 2022. You cannot join it, but the record below documents what was studied.
Get an email when the registry record changes — status, dates, results — or when someone posts here.
Sign in to followQuestions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.
Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.
Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.
University of Calgary