Phenylalanine, Methionine and Histidine Requirements in TPN Fed Neonates

Phenylalanine, Methionine and Histidine Requirements in Total Parenteral Nutrition (TPN) Fed Neonates

This is a single center project assessing the requirements for three essential amino acids in TPN fed neonates. Using the Carbon Oxidation method (indicator amino oxidation and direct amino acid oxidation method), the investigators will determine the requirement of each of the 3 amino acids. The investigators will first determine the requirement for Phenylalanine, then Methionine and finally Histidine. The investigators will recruit 18 - 20 babies per amino acid study. Breath and urine samples will be collected to determine the oxidation of the indicator amino acid. The response of the indicator amino acid to changes in intake of the test amino acid (phenylalanine, methionine, and histidine) will be analyzed by bi-phase linear mixed effect model to determine the breakpoint or mean requirement for each amino acid.

It is hypothesized that the requirement for phenylalanine, methionine and histidine will be at least 50% lower than what is currently available in commercial amino acids solutions used for TPN feeding of neonates.

Study Overview

• Status: Recruiting
• Conditions: Stable Neonates; Receiving Total Parenteral Nutrition (TPN)
• Intervention / Treatment: Drug: Total parenteral nutrition (TPN). This is total nutrition provided by central vein.

Detailed Description

The study is based on the carbon oxidation protocol. Each baby will receive one or two levels of either phenylalanine or methionine or histidine. Each level will be assessed over a two-day period.

On day 1: each baby will receive a standard pediatric amino acid solution, Primene used in the NICU and L-[1-13C]Na Bicarbonate will be given to measure carbon dioxide production. On day 2: he/she will receive the appropriate TPN Test Solution made up of the appropriate Bulk Amino Acid solution (for Phenylalanine/ Methionine/ Histidine Studies) with a different amount of the amino acid being investigated. To see how these amino acids are used in the body the investigators will add a small amount (calculated based on the body weight of the baby) of the amino acid L-[1-13C]phenylalanine to the amino acid solution. Breath and urine will be collected from the baby to study the oxidation of the L -[1-13C]phenylalanine. The investigators will take 2 x 0.75 ml blood to measure plasma amino acid concentration. The investigators will aim to coordinate blood taking with regular blood work done for clinical monitoring.

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Mahroukh Rafii; Phone Number: 6472151201; Email: mahroukh.rafii@sickkids.ca
• Study Contact Backup: Name: Glenda Courtney-Martin; Phone Number: 4168135744; Email: glenda.courtney-martin@sickkids.ca

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G 1X8
      • Recruiting
      • Glenda Courtney-Martin
      • Contact: Glenda Courtney-Martin; Phone Number: 4168135744; Email: glenda.courtney-martin@sickkids.ca

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 day to 4 weeks (Child)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Stable preterm babies that are growing and fully TPN fed (at least 90% of calories and protein).
2. TPN providing adequate calories and protein as determined by attending physician and dietitian.
3. Babies born ≥ 28 weeks gestation,
4. ≤ 28 days chronological age at the time of the study,
5. Birth weight and length appropriate for gestational age,
6. Medically stable as determined by normal blood results and lack of a fever or infection,
7. At least 3 days after surgery, if the baby had a surgery.

Exclusion Criteria:

1. Babies on mechanical ventilation, on low flow oxygen and CPAP.
2. Small for gestational age,
3. On medications known to affect protein and amino acid metabolism,
4. Documented infection, fever
5. Unstable medical condition
6. Receiving enteral feeding providing > 10% of protein intake.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Phenylalanine, methionine, histidine requirement	Drug: Total parenteral nutrition (TPN). This is total nutrition provided by central vein.; phenylalanine, methionine and histidine intakes will be varied in the TPN solutions to study the requirements for each of these amino acids in neonates that are TPN fed.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Amino acid oxidation using a labelled amino acid.	Breath samples will be collected and analyzed to determine the amount of amino acid oxidized. This will be used to determine the amount retained in the body and therefore the amount that is required for protein synthesis.	48 hrs

Collaborators and Investigators

• Sponsor: The Hospital for Sick Children

Study record dates

Study Major Dates

• Study Start (Actual): April 2, 2023
• Primary Completion (Estimated): September 2, 2026
• Study Completion (Estimated): September 2, 2027

Study Registration Dates

• First Submitted: September 22, 2022
• First Submitted That Met QC Criteria: September 27, 2022
• First Posted (Actual): September 30, 2022

Study Record Updates

• Last Update Posted (Actual): September 13, 2023
• Last Update Submitted That Met QC Criteria: September 11, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Keywords: Neonates; Phenylalanine; Methionine; Total parenteral nutrition (TPN); Histidine
• Other Study ID Numbers: 1000076474

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No