Intralipid Regimens for Neurodevelopment in Preterm Infants

Overseen By Lindsay F Holzapfel, MD, MS

Age: < 18

Sex: Any

Trial Phase: Phase 2

Sponsor: The University of Texas Health Science Center, Houston

Must not be taking: Intralipid

Disqualifiers: Congenital anomaly, Nonbacterial infection, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 14 days

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines how varying amounts of intralipid (a fat-based nutrient given through an IV) affect brain development in extremely preterm infants. Researchers aim to determine if reducing the usual intralipid amount can alter levels of unbound bilirubin (a blood substance) and enhance hearing and overall development by age two. The trial includes two groups: one receiving the usual prescribed intralipid (UL) regimen and the other receiving a restricted prescribed intralipid (RL) regimen. Infants eligible for this trial do not have major birth defects or infections and have mothers who agreed to participate in a related study. As a Phase 2 trial, this research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

Do I need to stop taking my current medications to join the trial?

The trial protocol does not specify whether you need to stop taking your current medications.

Will I have to stop taking my current medications?

The trial information does not specify whether participants need to stop taking their current medications.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that Intralipid treatments are generally safe for premature babies. For the restricted prescribed intralipid (RL) regimen, studies have found that long-term use might be linked to some liver problems, though these are uncommon. Side effects are rarely observed.

The usual prescribed intralipid (UL) regimen has undergone safety testing in many studies. Most infants tolerate common doses well. However, rare reports of serious side effects, such as breathing issues and metabolic imbalances, have occurred.

In both regimens, starting doses are usually well tolerated, and side effects are uncommon. Prospective trial participants should note that while intralipid treatments are generally safe, they do carry some risks, as with any treatment. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the trial comparing different intralipid regimens for preterm infants because it could lead to better neurodevelopmental outcomes. Unlike standard intralipid protocols, which may not account for the unique metabolic needs of preemies, the restricted prescribed intralipid (RL) regimen offers a tailored approach. This regimen aims to optimize nutrition while potentially reducing risks associated with overfeeding or underfeeding essential lipids. By fine-tuning the lipid intake, this method hopes to better support brain development in these vulnerable infants.

What evidence suggests that this trial's treatments could be effective for neurodevelopment in preterm infants?

Research has shown that varying the amounts of a fat-based nutrition called intralipid given to premature babies can affect their brain development and bilirubin levels. In this trial, participants will be assigned to one of two treatment arms: the restricted prescribed intralipid (RL) regimen or the usual prescribed intralipid (UL) regimen. Previous studies compared reduced fat intake to the usual amount and found that the usual amount might increase certain fats in the blood. This increase can displace bilirubin from a protein that carries it, potentially affecting brain development. However, the effects of reduced fat intake on brain development are still under investigation. This trial researches both approaches to understand their specific effects on the brain development of very premature babies. The goal is to find the best way to support growth while reducing risks. ^{2 3 4 6 7}

Who Is on the Research Team?

Lindsay F Holzapfel, MD, MS

Principal Investigator

The University of Texas Health Science Center, Houston

Are You a Good Fit for This Trial?

This trial is for extremely preterm infants without major birth defects or infections, whose mothers consented to the Neonatal Research Network Cycled Phototherapy Trial. Infants who have already received intralipid treatments are not eligible.

Inclusion Criteria

I do not have any major birth defects or active infections.

Mother has consented to inclusion of the infant for the Neonatal Research Network (NRN) Cycled Phototherapy Trial

Exclusion Criteria

I have received Intralipid treatment.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either the usual or reduced lipid intake to evaluate effects on bilirubin levels and neurodevelopmental outcomes

14 days

Follow-up

Participants are monitored for neurodevelopmental outcomes at 2 years

2 years

What Are the Treatments Tested in This Trial?

Interventions

• restricted prescribed intralipid (RL) regimen
• usual prescribed intralipid (UL) regimen

Trial Overview The study compares two lipid intake regimens in premature babies: a restricted and a usual prescribed intralipid regimen. It aims to see how these affect bilirubin levels, auditory brain responses, and neurodevelopment by age 2.

How Is the Trial Designed?

Group I: restricted prescribed intralipid (RL) regimen Experimental Treatment 1 Intervention

Group II: usual prescribed intralipid (UL) regimen Active Control 1 Intervention

restricted prescribed intralipid (RL) regimen is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Intralipid for:

• Parenteral nutrition for adults and pediatric patients

Approved in European Union as Intralipid for:

• Parenteral nutrition for adults and pediatric patients

Approved in Canada as Intralipid for:

• Parenteral nutrition for adults and pediatric patients

Who Is Running the Clinical Trial?

The University of Texas Health Science Center, Houston

Lead Sponsor

Trials

974

Recruited

361,000+

National Center for Advancing Translational Sciences (NCATS)

Collaborator

Trials

394

Recruited

404,000+

Published Research Related to This Trial

In a study of 262 preterm infants receiving parenteral nutrition, those given the multi-oil-based intravenous lipid emulsion (SMOFlipid) had a significantly shorter hospital stay compared to those receiving the conventional soybean oil-based emulsion (Intralipid).

The SMOFlipid group also showed lower rates of retinopathy of prematurity (ROP) at 23.8% compared to 37.5% in the Intralipid group, suggesting potential benefits in reducing this serious condition, although this difference was not significant in multivariate analysis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical effects of multi-oil versus pure soybean oil-based lipid emulsions for preterm infants: An observational study. Li, X., Zhao, R., Lv, HF., et al.[2023]

In a study of 170 very low birth weight premature infants, switching from Intralipid to SMOFlipid in parenteral nutrition was associated with a reduction in moderate to severe bronchopulmonary dysplasia (BPD) and cholestasis.

However, the use of SMOFlipid also correlated with an increase in late sepsis cases, particularly from Staphylococcus epidermidis, indicating a need for careful monitoring when using this alternative lipid emulsion.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Morbidity Outcomes of Very Low Birth Weight Neonates Receiving Parenteral Nutrition with Fish Oil Enriched Lipid Emulsion or Lipid Emulsion with Soybean Oil: An Observational Study. Uberos, J., Jiménez-Montilla, S., Molina-Oya, M., et al.[2021]

New intravenous lipid emulsions (IVLEs) that combine soybean oil with olive oil or fish oil may reduce the need for essential fatty acids while potentially lowering serum triglycerides, making them beneficial for patients with hypertriglyceridemia.

Despite historical concerns, recent evidence shows that fish oil in IVLEs does not increase bleeding risk, even in patients on anticoagulants, but these new emulsions provide less vitamin K, necessitating supplementation for patients receiving parenteral nutrition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dispelling myths about intravenous fish oil-based lipid emulsions: a clinical perspective. ApSimon, M.[2019]

The United States Pharmacopeia established strict criteria for lipid injectable emulsions, requiring a mean droplet diameter of less than 500 nm and a volume-weighted percentage of fat greater than 5 microm (PFAT(5)) to be less than 0.05%.

A study of 31 lots of Intralipid over five years showed that after reformulation, the product successfully transitioned from a coarse to a fine dispersion, meeting the new pharmacopeial limits for safety and efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The pharmacopeial evolution of intralipid injectable emulsion in plastic containers: from a coarse to a fine dispersion. Driscoll, DF.[2010]

Intravenous lipid emulsions (ILEs) provide essential calories and fatty acids that are crucial for the growth and health of preterm infants and those with intestinal failure.

The type and dosage of ILEs influence the delivery of important nutrients like fatty acids and vitamins, which can affect the risk of deficiencies and support overall neonatal health, including inflammation and organ development.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Parenteral Nutrition in the Neonatal Intensive Care Unit: Intravenous Lipid Emulsions. Chan, AP., Rostas, S., Rogers, S., et al.[2023]

In a study of 37 neonates with intestinal failure, those receiving SMOFlipid had significantly lower levels of conjugated bilirubin, indicating better liver function compared to those receiving Intralipid.

Patients on SMOFlipid also showed improved weight gain at 3 and 6 months, suggesting that SMOFlipid may be more effective in supporting overall growth and reducing liver disease associated with intestinal failure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An Observational Study of Smoflipid vs Intralipid on the Evolution of Intestinal Failure-Associated Liver Disease in Infants With Intestinal Failure. Belza, C., Wales, JC., Courtney-Martin, G., et al.[2021]

Intravenous lipid emulsions (ILEs) are crucial for the growth of very preterm and very low birth weight infants, with doses of 1.5-2 g/kg/day advancing to 3 g/kg/day showing enhanced growth without significant differences between 100% soybean oil and multi-oil emulsions.

100% fish oil is recommended for treating parenteral nutrition-associated cholestasis and liver disease, but further research is needed to optimize ILEs for better neurodevelopment outcomes and to establish clear guidelines for managing hypertriglyceridemia in this vulnerable population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dilemmas in the delivery of intravenous lipid emulsions and approach to hypertriglyceridemia in very preterm and low birth weight infants. Frost, B., Martin, CR., Calkins, KL.[2023]

Citations

1. withpower.com withpower.com/trial/phase-3-kernicterus-2021-1340c

Intralipid Regimens for Neurodevelopment in Preterm Infants Trial Overview The study compares two lipid intake regimens in premature babies: a restricted and a usual prescribed intralipid regimen. It aims to see how ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S1744165X25000290

Parenteral nutrition for preterm infants: benefits and risks in ... Parenteral nutrition (PN) has been a key component of neonatal care for preterm infants since the 1980's and provides macronutrients for growth.

3. bmcpediatr.biomedcentral.com bmcpediatr.biomedcentral.com/articles/10.1186/s12887-023-04149-0

Effect of reduced versus usual lipid emulsion dosing on ... This pilot study addresses whether a commonly used pure soybean-based intravenous lipid emulsion dosing regimen increases the risk BN toxicity ...

4. mdpi.com mdpi.com/2072-6643/15/1/58

Neurodevelopmental Outcomes in Preterm Infants ... The administration of a multicomponent LE containing fish oil, compared to a soybean-based LE, had no significant effects on neurodevelopmental outcomes in ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7265279/

Parenteral Fish-Oil Lipid Emulsions in Retinopathy ... Purpose: To evaluate the effects of a fish oil-containing regimen on the severity of retinopathy of prematurity (ROP) in preterm infants.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4325703/

Intravenous Lipids for Preterm Infants: A Review - PMC However, when provided in 8-hour regimen, levels of over 300 mg/dL were seen, especially in the <32-week premature infants. The practice of increasing ...

7. hopkinsmedicine.org hopkinsmedicine.org/-/media/files/allchildrens/clinical-pathways/iv-lipid-emulsions-management-clinical-pathway-5_3_24.pdf

Intravenous Lipid Emulsions Management Clinical Pathway Despite limited data on the benefit of SMOF, adverse effects are unlikely and the prolonged use of Intralipid is associated with PNALD. When ...