Bilirubin Neurotoxicity (BN) and Neurodevelopmental Impairment (NDI) in Extremely Preterm (EP) Infants: Avoidable by Reducing the Usual Intravenous Lipid (UL) Administration

The purpose of this study is to evaluate the effect of usual versus reduced lipid intake on unbound bilirubin levels, brainstem auditory evoked responses, and neurodevelopmental outcome at 2 years in extremely preterm infants.

Study Overview

• Status: Recruiting
• Conditions: Bilirubin Encephalopathy
• Intervention / Treatment: Drug: usual prescribed intralipid (UL) regimen; Drug: restricted prescribed intralipid (RL) regimen

• Study Type: Interventional
• Enrollment (Estimated): 120
• Phase: Phase 2

Contacts and Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 6 months (Child)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• no major congenital anomaly or overt nonbacterial infection
• mother has consented to inclusion of the infant for the Neonatal Research Network (NRN) Cycled Phototherapy Trial

Exclusion Criteria:

• has received Intralipid

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: usual prescribed intralipid (UL) regimen	Drug: usual prescribed intralipid (UL) regimen; Intralipid will be started at 1 g/kg/day and routinely advanced by 1 g/kg/day each day to a max of 3 g/kg/day as per usual clinical practice
Experimental: restricted prescribed intralipid (RL) regimen	Drug: restricted prescribed intralipid (RL) regimen; Intralipid will be started at 0.5 g/kg/day and routinely advanced by 0.5 g/kg/day each day to a max of 1.5 g/kg/day (half rate of usual clinical practice).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of patients with unbound bilirubin (UB) concentration greater than 40 nM/L		within first 14 days of life
Average unbound bilirubin (UB) concentration	6 UB measurements will be taken per participant .Average of the 6 readings will be reported	within first 14 days of life
Number of patients with a prolonged brain stem auditory-evoked response (BAER) V latency		34-36 weeks post menstrual age(PMA)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean UB concentration		within first 14 days of life
Number of patients with UB measurements greater than 40 nM/L		within first 14 days of life
Peak UB concentration		within first 14 days of life
Total unbound free fatty acids (FFA)	6 FFA measurements will be taken for each participant.Average of the 6 readings will be reported	within first 14 days of life
Peak total unbound free fatty acids (FFA)		within first 14 days of life
Peak total serum bilirubin		within first 14 days of life
Number of patients with Direct bilirubin greater than 1.5 mg/dL		Before discharge (discharge is on average 3 months after birth)
Amount of protein given to participant in grams per kilograms per day		within first 14 days of life
Amount of carbohydrates given to participant in grams per kilograms per day		within first 14 days of life
Amount of fats given to participant in grams per kilograms per day		within first 14 days of life
Change in weight(grams/kilogram/day)		birth,day 28
Change in weight(grams/kilogram/day)		birth,post menstrual age 36 weeks
Number of patients with Bronchopulmonary dysplasia		36 weeks post menstrual age
number of patients with Perinatal and hospital acquired sepsis episodes		birth until discharge ( discharge will be about 3 months post birth)
Number of patients who died		24 months PMA
Number of patients with neurodevelopmental impairment		24 months PMA
Number of patients with hearing loss		24 months PMA
Number of patients with cerebral palsy		24 months PMA

Collaborators and Investigators

• Sponsor: The University of Texas Health Science Center, Houston
• Collaborators: National Center for Advancing Translational Sciences (NCATS)
• Investigators: Principal Investigator: Lindsay F Holzapfel, MD, MS, The University of Texas Health Science Center, Houston

Publications and helpful links

General Publications

• Holzapfel LF, Arnold C, Tyson JE, Shapiro SM, Reynolds EW, Pedroza C, Stephens EK, Kleinfeld A, Huber AH, Rysavy MA, Del Mar Romero Lopez M, Khan AM. Effect of reduced versus usual lipid emulsion dosing on bilirubin neurotoxicity and neurodevelopmental impairment in extremely preterm infants: study protocol for a randomized controlled trial. BMC Pediatr. 2023 Jul 10;23(1):347. doi: 10.1186/s12887-023-04149-0.

Study record dates

Study Major Dates

• Study Start (Actual): January 6, 2021
• Primary Completion (Estimated): June 30, 2024
• Study Completion (Estimated): June 30, 2026

Study Registration Dates

• First Submitted: October 6, 2020
• First Submitted That Met QC Criteria: October 6, 2020
• First Posted (Actual): October 14, 2020

Study Record Updates

• Last Update Posted (Actual): August 7, 2023
• Last Update Submitted That Met QC Criteria: August 2, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Keywords: preterm; bilirubin; lipid emulsions; unbound bilirubin; unbound free fatty acids
• Additional Relevant MeSH Terms: Chemically-Induced Disorders; Pathologic Processes; Metabolic Diseases; Central Nervous System Diseases; Nervous System Diseases; Immune System Diseases; Hematologic Diseases; Infant, Newborn, Diseases; Brain Diseases, Metabolic; Poisoning; Hyperbilirubinemia; Erythroblastosis, Fetal; Brain Diseases; Neurotoxicity Syndromes; Kernicterus; Pharmaceutical Solutions; Parenteral Nutrition Solutions; Fat Emulsions, Intravenous; Soybean oil, phospholipid emulsion
• Other Study ID Numbers: HSC-MS-20-0916; KL2TR003168 (U.S. NIH Grant/Contract)

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