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

134 Participants Needed

Trial Summary

What is the purpose of this trial?

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.

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.

What data supports the idea that Intralipid Regimens for Neurodevelopment in Preterm Infants is an effective treatment?

The available research shows that Intralipid, a soybean oil-based intravenous lipid emulsion, is commonly used in parenteral nutrition for preterm infants. However, studies comparing Intralipid to other lipid emulsions like SMOFlipid, which includes fish oil, suggest that SMOFlipid may have some advantages. For instance, one study found that using SMOFlipid resulted in fewer cases of certain health issues like bronchopulmonary dysplasia and cholestasis compared to Intralipid. This suggests that while Intralipid is effective, there might be alternative treatments that offer better outcomes for specific conditions. ^{1 2 3 4 5}

What data supports the effectiveness of the treatment Intralipid Regimens for Neurodevelopment in Preterm Infants?

Research suggests that intravenous lipid emulsions, like Intralipid, are essential for growth in very preterm and low birth weight infants, as they enhance growth when given at specific doses. However, there is no direct evidence from the provided studies that these emulsions improve neurodevelopment outcomes in preterm infants. ^{1 2 3 4 5}

What safety data exists for Intralipid regimens in preterm infants?

The safety data for Intralipid regimens in preterm infants includes several studies and observations. Intralipid, a soybean oil-based intravenous lipid emulsion, has been commonly used in parenteral nutrition. Studies have compared its effects with other lipid emulsions like SMOFlipid, which contains fish oil and has a different fatty acid profile. Research indicates that while Intralipid is effective for growth, SMOFlipid may reduce the prevalence of certain conditions like bronchopulmonary dysplasia and cholestasis, though it may increase the risk of late sepsis. Additionally, the formulation of Intralipid has evolved to meet pharmacopeial specifications for droplet size, ensuring its safety and efficacy. However, there is still a need for further research to optimize lipid emulsions for neurodevelopment and manage complications like hypertriglyceridemia in preterm infants. ^{1 2 3 4 5}

Is Intralipid safe for use in preterm infants?

Intralipid, a soybean oil-based intravenous lipid emulsion, has been widely used in preterm infants and is generally considered safe. However, some studies suggest that alternative formulations like SMOFlipid may reduce certain complications such as bronchopulmonary dysplasia and cholestasis, although they may increase the risk of late sepsis. Overall, Intralipid is a common component of parenteral nutrition for preterm infants, but ongoing research is needed to optimize its use and safety. ^{1 2 3 4 5}

Is the Intralipid regimen a promising treatment for neurodevelopment in preterm infants?

Intralipid, a soybean oil-based intravenous lipid emulsion, is commonly used in preterm infants to support growth and provide essential nutrients. It helps deliver nonprotein calories and fatty acids, which are important for growth and development. While Intralipid is effective in promoting growth, newer formulations like SMOFlipid, which include a mix of oils, may offer additional benefits such as improved liver health and reduced risk of certain complications. However, Intralipid remains a valuable option for supporting the growth and development of preterm infants. ^{1 2 5 6 7}

How does the Intralipid regimen for preterm infants differ from other treatments?

The Intralipid regimen for preterm infants is unique because it uses a 100% soybean oil-based intravenous lipid emulsion, which is a common component of parenteral nutrition to support growth and development in these infants. Unlike multi-oil emulsions like SMOFlipid, Intralipid has a specific omega-6 to omega-3 ratio and lower vitamin E content, which may influence its effects on conditions like cholestasis and bronchopulmonary dysplasia. ^{1 2 5 6 7}

Research Team

Lindsay F Holzapfel, MD, MS

Principal Investigator

The University of Texas Health Science Center, Houston

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

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]

References

1. China pubmed.ncbi.nlm.nih.gov

Clinical effects of multi-oil versus pure soybean oil-based lipid emulsions for preterm infants: An observational study. [2023]

2. United States 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. [2023]

3. Netherlands pubmed.ncbi.nlm.nih.gov

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

4. England pubmed.ncbi.nlm.nih.gov

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

5. United States 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. [2021]

6. United States pubmed.ncbi.nlm.nih.gov

Parenteral Nutrition in the Neonatal Intensive Care Unit: Intravenous Lipid Emulsions. [2023]

7. United States 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. [2021]