Isoleucine, Leucine, Valine and Tryptophan Requirements in TPN Fed Neonates

Isoleucine, Leucine, Valine and Tryptophan Requirements in Total Parenteral Nutrition (TPN) Fed Neonates

This project will be conducted in 2 hospitals in Brazil to assess the requirements for four 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 4 amino acids.

The investigators will determine the requirement for Isoleucine, Leucine, Valine and Tryptophan. 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 (isoleucine, leucine, valine and tryptophan) 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 isoleucine, leucine, valine and tryptophan will be at least 50% lower than what is currently available in commercial solutions used for TPN feeding of neonates.

Study Overview

• Status: Recruiting
• Conditions: Stable Neonates; Neonates on TPN; Neonates Managed in the ICU
• 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 isoleucine or leucine or valine or tryptophan. 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 Isoleucine/ Leucine/ Valine/ Tryptophan 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 routine blood work done for clinical monitoring.

• Study Type: Interventional
• Enrollment (Estimated): 80
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Mahroukh Rafii, BSc; Phone Number: 4168137454; Email: mahroukh.rafii@sickkids.ca
• Study Contact Backup: Name: Glenda Courtney-Martin, PhD; Phone Number: 416 813 5744; Email: glenda.courtney-martin@sickkids.ca

Study Locations

• Brazil
  • Santa Maria, Brazil
    • Recruiting
    • Hospital de Caridade Dr. Astrogildo de Azevedo, and University Hospital of Santa Maria, Santa Maria, Brazil
    • Contact: Ivo Dr Prola, MD, PhD; Phone Number: 6477815786; Email: iprolla@gmail.com
    • Contact: Beatriz Dr Porto, MD; Phone Number: 6475002171; Email: bsilveiraporto@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 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: Isoleucine, leucine, valine, tryptophan requirement; isoleucine, leucine, valine and tryptophan intakes will be varied in the TPN solutions to study the requirements for each of these amino acids in neonates that are TPN fed.	Drug: Total parenteral nutrition (TPN): this is total nutrition provided by central vein.; isoleucine, leucine, valine and tryptophan 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 ofamino acid oxidized. This will be used to determine the amount retained inthe 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): January 1, 2026
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): December 1, 2027

Study Registration Dates

• First Submitted: April 15, 2024
• First Submitted That Met QC Criteria: April 15, 2024
• First Posted (Actual): April 18, 2024

Study Record Updates

• Last Update Posted (Actual): April 2, 2026
• Last Update Submitted That Met QC Criteria: March 27, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: neonates; parenteral nutrition; leucine; tryptophan; isoleucine; Neonates, Total pareteral nutrition (TPN), Isoleucine, Leucine, Valine, Tryptophan; valine
• Additional Relevant MeSH Terms: Signs and Symptoms, Digestive; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Hyperphagia; Therapeutics; Nutrition Therapy; Feeding Methods; Nutritional Support; Parenteral Nutrition; Parenteral Nutrition, Total
• Other Study ID Numbers: 1000081221

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: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No