Lipid Infusions to Optimize Nutrition Trial (LION)

Lipid Infusions to Optimize Nutrition (LION) and Minimize Bronchopulmonary Dysplasia and Neurodevelopmental Impairment in Extremely Preterm Infants: A Randomized Comparative Effectiveness Trial

The purpose of this study is to identify survival free of bronchopulmonary dysplasia (BPD), fatty acid profiles, and early biochemical measures for oxidative stress comparing mixed oil lipid emulsion (MOLE) vs soybean oil-based lipid emulsion (SOLE) and to establish whether MOLE or SOLE is more effective in minimizing pulmonary outcomes, neonatal morbidities, long-term morbidity and mortality, and improving discharge growth and Bayley Scales of Infant Development Fourth Edition (BSID-IV) neurodevelopmental assessment at two years

Study Overview

• Status: Recruiting
• Conditions: Bronchopulmonary Dysplasia; Neurodevelopmental Impairment
• Intervention / Treatment: Drug: SOLE; Drug: MOLE

• Study Type: Interventional
• Enrollment (Estimated): 230
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Emily Stephens; Phone Number: (713) 500-5734; Email: Emily.K.Stephens@uth.tmc.edu
• Study Contact Backup: Name: Lindsay F Holzapfel, MD, MS; Phone Number: (713) 500-6422; Email: Lindsay.N.Fleig@uth.tmc.edu

Study Locations

• United States
  • Texas
    • Houston, Texas, United States, 77030
      • Recruiting
      • The University of Texas Health Science Center at Houston
      • Contact: Emily Stephens; Phone Number: (713) 500-5734; Email: Emily.K.Stephens@uth.tmc.edu
      • Contact: Lindsay Holzapfel, MD, MS; Phone Number: 713-500-6422; Email: Lindsay.N.Fleig@uth.tmc.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• inborn <28 weeks gestational age (GA) or ≤1000g birth weight (BW)
• survives until 12 hours after birth.

Exclusion Criteria:

• Infants who are unable to be enrolled by 96 hours postnatal age
• Major anomaly
• Overt non-bacterial infection
• Infants likely to expire soon defined as limiting or withdrawal of intensive care recommended or requested by the parents.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: SOLE	Drug: SOLE; Participants will first receive LE at 1 g/kg/day, then will advance to 2 g/kg/day and lastly to 3 g/kg/day as tolerated to titrate based on triglyceride level <250 mg/dL, per clinical team
Active Comparator: MOLE	Drug: MOLE; Participants will first receive LE at 1 g/kg/day, then will advance to 2 g/kg/day and lastly to 3 g/kg/day as tolerated to titrate based on triglyceride level <250 mg/dL, per clinical team

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Number of participants free of BPD (infants breathing in room air)	36 weeks post menstrual age (PMA)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in relative mole percentages of Docosahexaenoic acid (DHA) in plasma		baseline before LE exposure, end of the intervention period (28±3 postnatal days), 36 weeks postmenstrual age (±3 days)
Relative mole percentages of Docosahexaenoic acid (DHA) in plasma		baseline before LE exposure
Relative mole percentages of Docosahexaenoic acid (DHA) in plasma		end of the intervention period (28±3 postnatal days)
Relative mole percentages of Docosahexaenoic acid (DHA) in plasma		36 weeks postmenstrual age (±3 days)
Change in relative mole percentages of Eicosapentaenoic acid (EPA) in plasma		baseline before LE exposure, end of the intervention period (28±3 postnatal days), 36 weeks postmenstrual age (±3 days)
Relative mole percentages of Eicosapentaenoic acid (EPA) in plasma		baseline before LE exposure
Relative mole percentages of Eicosapentaenoic acid (EPA) in plasma		end of the intervention period (28±3 postnatal days)
Relative mole percentages of Eicosapentaenoic acid (EPA) in plasma		36 weeks postmenstrual age (±3 days)
Change in relative mole percentages of Arachidonic acid (ARA) in plasma		baseline before LE exposure, end of the intervention period (28±3 postnatal days), 36 weeks postmenstrual age (±3 days)
Relative mole percentages of Arachidonic acid (ARA) in plasma		baseline before LE exposure
Relative mole percentages of Arachidonic acid (ARA) in plasma		end of the intervention period (28±3 postnatal days)
Relative mole percentages of Arachidonic acid (ARA) in plasma		36 weeks postmenstrual age (±3 days)
Change in relative mole percentages of linoleic acid (LA) in plasma		baseline before LE exposure, end of the intervention period (28±3 postnatal days), 36 weeks postmenstrual age (±3 days)
Relative mole percentages of linoleic acid (LA) in plasma		baseline before LE exposure
Change in relative mole percentages of linoleic acid (LA) in plasma		end of the intervention period (28±3 postnatal days)
Change in relative mole percentages of linoleic acid (LA) in plasma		36 weeks postmenstrual age (±3 days)
Change in Urine oxidative stress marker, superoxide dismutase		baseline before LE exposure, end of the intervention period (28±3 postnatal days), 36 weeks postmenstrual age (±3 days)
Change in Urine oxidative stress marker, lipid peroxidase		baseline before LE exposure, end of the intervention period (28±3 postnatal days), 36 weeks postmenstrual age (±3 days)
Change in glutathione ratio		baseline before LE exposure, end of the intervention period (28±3 postnatal days), 36 weeks postmenstrual age (±3 days)
Amount of superoxide dismutase		baseline before LE exposure
Amount of superoxide dismutase		end of the intervention period (28±3 postnatal days)
Amount of superoxide dismutase		36 weeks postmenstrual age (±3 days)
Glutathione ratio		baseline before LE exposure
Glutathione ratio		end of the intervention period (28±3 postnatal days)
Glutathione ratio		36 weeks postmenstrual age (±3 days)
Amount of lipid peroxidase		baseline before LE exposure
Amount of lipid peroxidase		end of the intervention period (28±3 postnatal days)
Amount of lipid peroxidase		36 weeks postmenstrual age (±3 days)
Change in lung reactance as assessed by the Non-Invasive Functional Oscillometry Test (FOT)		before discharge (~ 36 weeks post menstrual age), two years
Change in resistance as assessed by the Non-Invasive Functional Oscillometry Test (FOT)		before discharge (~ 36 weeks post menstrual age), two years
Change in impedance as assessed by the Non-Invasive Functional Oscillometry Test (FOT)		before discharge (~ 36 weeks post menstrual age), two years
Change in resonance frequency as assessed by the Non-Invasive Functional Oscillometry Test (FOT)		before discharge (~ 36 weeks post menstrual age), two years
Change in tidal volume as assessed by the Non-Invasive Functional Oscillometry Test (FOT)		before discharge (~ 36 weeks post menstrual age), two years
Change in respiratory rate as assessed by the Non-Invasive Functional Oscillometry Test (FOT)		before discharge (~ 36 weeks post menstrual age), two years
Change in weight of participant		baseline, end of the intervention period (28±3 postnatal days), 36 weeks postmenstrual age, at discharge (~ 40 weeks post menstrual age)
Change in length of participant		baseline, end of the intervention period (28±3 postnatal days), 36 weeks postmenstrual age, at discharge (~ 40 weeks post menstrual age)
Change in head circumference of participant		baseline, end of the intervention period (28±3 postnatal days), 36 weeks postmenstrual age, at discharge (~ 40 weeks post menstrual age)
Neurodevelopmental development as assessed by the Bayley Scales of Infants Development Version IV (BSID-IV)	The following domains will be assessed: composite motor, language and cognition.Range of composite score is from 40-160.Composite scores (mean = 100; Standard Deviation = 15) will be reported, with higher scores reflecting better developmental outcomes.	2 years corrected age
Mechanical ventilation days		Discharge (about 3 months from birth)
Number of days participants are exposed to oxygen		Discharge (about 3 months from birth)
Number of chronic lung disease re-hospitalizations		after Neonatal Intensive Care Unit (NICU) discharge till 2 years of age
Number of participants that develop late onset sepsis		Discharge (about 3 months from birth)
Number of participants that develop cholestasis		Discharge (about 3 months from birth)
Weight of participant		Discharge (about 3 months from birth)
Length of participant		Discharge (about 3 months from birth)
Head circumference of participant		Discharge (about 3 months from birth)
Number of participants that die		Discharge (about 3 months from birth)
Number of participants that die		at 2 years
Number of participants that develop Neonatal Morbidity	Neonatal Morbidity may include severe intraventricular hemorrhage, surgical necrotizing enterocolitis (stage 2A or greater), severe retinopathy of prematurity (Stage 2 or greater or with plus disease), hearing loss, severe bronchopulmonary dysplasia or death.	Discharge (about 3 months from birth)

Collaborators and Investigators

• Sponsor: The University of Texas Health Science Center, Houston
• Investigators: Principal Investigator: Lindsay Holzapfel, MD, MS, The University of Texas Health Science Center, Houston

Study record dates

Study Major Dates

• Study Start (Estimated): May 1, 2026
• Primary Completion (Estimated): July 30, 2028
• Study Completion (Estimated): December 31, 2030

Study Registration Dates

• First Submitted: March 27, 2025
• First Submitted That Met QC Criteria: April 3, 2025
• First Posted (Actual): April 8, 2025

Study Record Updates

• Last Update Posted (Actual): May 5, 2026
• Last Update Submitted That Met QC Criteria: April 29, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: soybean oil-based lipid emulsion (SOLE); mixed oil lipid emulsion (MOLE)
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases; Infant, Premature, Diseases; Infant, Newborn, Diseases; Lung Injury; Ventilator-Induced Lung Injury; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Bronchopulmonary Dysplasia
• Other Study ID Numbers: HSC-MS-24-1129

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No