Amino Acid Requirements in TPN for Neonates

Age: < 18

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Academic

Recruiting

Sponsor: The Hospital for Sick Children

Must not be taking: Protein metabolism drugs

Disqualifiers: Mechanical ventilation, Infection, Enteral feeding, others

No Placebo Group

Trial Summary

What is the purpose of this trial?

This trial tests how much of three important nutrients newborns need when fed through a tube. It focuses on babies who rely on this type of nutrition and uses a method to see how their bodies use these nutrients.

Will I have to stop taking my current medications?

The trial requires that participants are not on medications known to affect protein and amino acid metabolism. If your current medications affect these, you may need to stop them to participate.

What data supports the effectiveness of the treatment involving Histidine, L-Histidine, Methionine, DL-Methionine, L-Methionine, Phenylalanine, and L-Phenylalanine in TPN for neonates?

Research shows that adjusting amino acid levels in total parenteral nutrition (TPN) can help achieve more normal plasma amino acid patterns in infants, which may improve their overall nutrition and growth. Specifically, studies on phenylalanine and tyrosine in neonatal piglets suggest that understanding and meeting specific amino acid requirements is crucial for effective TPN. ^{1 2 3 4 5}

How does the treatment of Histidine, Methionine, and Phenylalanine in TPN for neonates differ from other treatments?

This treatment is unique because it focuses on the specific amino acid requirements for neonates receiving total parenteral nutrition (TPN), which are different from those for oral feeding. The study highlights the importance of determining precise amino acid needs, such as phenylalanine, to improve TPN formulations for better nutritional outcomes in neonates. ^{1 2 4 6 7}

Research Team

Eligibility Criteria

This trial is for stable newborns who are the right size for their age, born at or after 28 weeks of pregnancy, and are under 28 days old. They must be mostly fed through a vein (at least 90% of calories and protein) and not have any infections or serious health issues.

Inclusion Criteria

Birth weight and length appropriate for gestational age

My baby was born at or after 28 weeks of pregnancy.

My baby is stable, growing, and mostly fed through IV nutrition.

Exclusion Criteria

My baby is on a breathing machine or needs extra oxygen.

Receiving enteral feeding providing > 10% of protein intake

Small for gestational age

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Each baby receives one or two levels of either phenylalanine, methionine, or histidine over a two-day period. Day 1 involves a standard pediatric amino acid solution, and Day 2 involves a TPN Test Solution with the amino acid being investigated.

2 days per amino acid

Daily visits for sample collection

Follow-up

Participants are monitored for safety and effectiveness after treatment

1-2 weeks

Treatment Details

Interventions

• Histidine (Amino Acid)
• Methionine (Amino Acid)
• Phenylalanine (Amino Acid)

Trial Overview The study is testing how much of three amino acids - Phenylalanine, Methionine, Histidine - neonates need when they're getting all their nutrition through a vein. Researchers will use special methods to measure these needs in about 18-20 babies per amino acid.

Participant Groups

Group I: Phenylalanine, methionine, histidine requirement Experimental Treatment 1 Intervention

Histidine is already approved in Canada, Japan for the following indications:

Approved in Canada as L-Histidine for:

• Nutritional supplement in parenteral nutrition

Approved in Japan as L-Histidine for:

• Nutritional supplement in parenteral nutrition

Who Is Running the Clinical Trial?

The Hospital for Sick Children

Lead Sponsor

Trials

724

Recruited

6,969,000+

Dr. Ronald D. Cohn

The Hospital for Sick Children

Chief Executive Officer since 2019

MD from University of Düsseldorf, Germany

Dr. Lennox Huang

The Hospital for Sick Children

Chief Medical Officer since 2016

MD from McGill University

Findings from Research

This study determined that neonatal piglets require approximately 0.45 g of phenylalanine per kg of body weight per day when receiving total parenteral nutrition (TPN), with a safe intake level of 0.48 g/kg/d, which is crucial for optimizing TPN formulations.

The research utilized phenylalanine oxidation techniques to assess amino acid requirements, revealing that higher intakes above 0.8 g/kg/d do not lead to a proportional increase in oxidation, indicating a limit to how much phenylalanine can be effectively utilized.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phenylalanine requirements determined by using L-[1-14C]phenylalanine in neonatal piglets receiving total parenteral nutrition supplemented with tyrosine. House, JD., Pencharz, PB., Ball, RO.[2018]

A new amino acid solution (AF) designed for infants on total parenteral nutrition (TPN) resulted in more balanced plasma amino acid levels compared to a commercially prepared solution (CF), which caused imbalances in certain amino acids.

Infants receiving the AF solution had a better nitrogen balance (+170 mg/kg/day) compared to those on CF (+112 mg/kg/day), suggesting that AF may be a more effective nutritional option for infants requiring TPN.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Total parenteral nutrition with a new amino acid solution for infants. Kanaya, S., Nose, O., Harada, T., et al.[2019]

In a study involving 18 neonatal piglets over 8 days, the control group receiving phenylalanine (Phe) showed significantly better nitrogen balance and utilization compared to those receiving N-acetyltyrosine (N-AcTyr) or glycyltyrosine (GlyTyr).

N-AcTyr was found to have low bioavailability, with 65% excreted in urine, indicating that current methods for supplying aromatic amino acids in total parenteral nutrition (TPN) for infants may need improvement.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Aromatic amino acid metabolism of neonatal piglets receiving TPN: effect of tyrosine precursors. Wykes, LJ., House, JD., Ball, RO., et al.[2017]

In a study involving 25 male Yorkshire piglets, the parenteral threonine requirement for neonates receiving total parenteral nutrition (TPN) was found to be significantly lower than that for those fed orally, with a mean requirement of 0.19 g/(kg.d) for TPN compared to 0.42 g/(kg.d) for oral feeding.

The research indicates that neonates on TPN need about 45% of the threonine that orally fed neonates require, highlighting the importance of adjusting amino acid intake based on feeding method to ensure proper nutrition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Threonine requirement of neonatal piglets receiving total parenteral nutrition is considerably lower than that of piglets receiving an identical diet intragastrically. Bertolo, RF., Chen, CZ., Law, G., et al.[2018]

Infants receiving total parenteral nutrition (TPN) often have low levels of tyrosine (Tyr) and high levels of phenylalanine (Phe), which can limit their ability to synthesize important biomolecules like proteins and catecholamines.

The study found that substituting half of the Phe in TPN with the soluble peptide gamma-glutamyl-tyrosine (Glu(Tyr)) resulted in normal plasma Tyr concentrations and improved Phe/Tyr ratios, suggesting that Glu(Tyr) could enhance Tyr availability for brain function in TPN formulations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of the soluble peptide gamma-L-glutamyl-L-tyrosine to provide tyrosine in total parenteral nutrition in rats. Radmacher, PG., Hilton, MA., Hilton, FK., et al.[2017]

In a study involving 26 TPN-fed piglets, the indicator amino acid oxidation (IAAO) technique revealed that adding limiting amino acids significantly reduced lysine oxidation, indicating improved amino acid utilization.

Specifically, the addition of aromatic amino acids (AAA) to one diet and sulfur amino acids (SAA) to another both led to a 30% decrease in lysine oxidation, demonstrating the effectiveness of this method in identifying and addressing amino acid deficiencies in parenteral nutrition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The indicator amino acid oxidation method identified limiting amino acids in two parenteral nutrition solutions in neonatal piglets. Brunton, JA., Shoveller, AK., Pencharz, PB., et al.[2023]

This study determined that the total sulfur amino acid (TSAA) requirement for postsurgical neonates receiving parenteral nutrition is approximately 47.4 to 49.0 mg/kg/day, using a method that measures amino acid oxidation.

The findings suggest that current commercial pediatric parenteral nutrition solutions provide about 90% of the estimated methionine requirement, indicating that these solutions may need adjustments to meet the specific needs of these vulnerable patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Total sulfur amino acid requirement and metabolism in parenterally fed postsurgical human neonates. Courtney-Martin, G., Chapman, KP., Moore, AM., et al.[2023]

References

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

Phenylalanine requirements determined by using L-[1-14C]phenylalanine in neonatal piglets receiving total parenteral nutrition supplemented with tyrosine. [2018]

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

Total parenteral nutrition with a new amino acid solution for infants. [2019]

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

Aromatic amino acid metabolism of neonatal piglets receiving TPN: effect of tyrosine precursors. [2017]

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

Threonine requirement of neonatal piglets receiving total parenteral nutrition is considerably lower than that of piglets receiving an identical diet intragastrically. [2018]

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

Use of the soluble peptide gamma-L-glutamyl-L-tyrosine to provide tyrosine in total parenteral nutrition in rats. [2017]

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

The indicator amino acid oxidation method identified limiting amino acids in two parenteral nutrition solutions in neonatal piglets. [2023]

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

Total sulfur amino acid requirement and metabolism in parenterally fed postsurgical human neonates. [2023]