Validating IAAO for Muscle Outcomes

NCT07317921 | Recruiting

• 1 other identifier: VIM
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 1

Brief Summary

Consuming dietary protein stimulates whole-body and muscle protein synthesis, the latter of which is typically measured using invasive primed constant infusions of stable isotopes with concurrent muscle biopsies. Alternative non-invasive methodologies have been developed (namely the indicator amino acid oxidation (IAAO) technique) to estimate the impact of protein ingestion on whole-body protein synthesis as a proxy for determining dietary protein requirements. Given that the IAAO technique is based on principles of protein metabolism which occur in the liver, it is unclear how representative the IAAO outcomes of whole-body protein synthesis is to skeletal muscle protein synthesis. Validation of the IAAO technique against gold-standard, biopsy-derived measures of muscle metabolism (i.e., muscle protein synthesis) would assist in mitigating the invasiveness of muscle physiology and nutrition research.

Conditions

Protein Metabolism

Keywords

Muscle biopsy; Protein Metabolism; Stable isotopes; Protein oxidation; Indicator amino acid oxidation; Protein synthesis

Outcome Measures

Primary Outcomes (4)

• Phenylalanine excretion (umol/kg/h)

  Rate of whole-body phenylalanine excretion following orally ingested amino acid tracer \[1-13C\]Phenylalanine determined from the product of breath 13CO2 enrichment and carbon dioxide production rate (VCO2).

  6.5 hours

• Phenylalanine oxidation (umol/kg/h)

  Rate of whole-body phenylalanine oxidation following orally ingested amino acid tracer \[1-13C\]Phenylalanine determined from the correction of phenylalanine excretion by the phenylalanine precursor enrichment via urine enrichment.

  6.5 hours

• Myofibrillar protein synthesis (%/hr)

  Rate of myofibrillar fractional synthesis is determined by rate of incorporation of orally ingested tracer \[2H5\]Phenylalanine into myofibrillar proteins (isolated from skeletal muscle biopsies) and the enrichment of \[2H5\]Phenylalanine in plasma collected over the 6 hours protein consumption period. Enrichment will be quantified via tandem LC-MS/MS to derive a rate of incorporation over the 6-hour period.

  6.5 hours

• Sarcoplasmic protein synthesis (%/hr)

  Rate of sarcoplasmic fractional synthesis is determined by rate incorporation of orally ingested tracer \[2H5\]Phenylalanine into sarcoplasmic (ie., soluble) proteins (isolated from skeletal muscle biopsies) and the enrichment of \[2H5\]Phenylalanine in plasma collected over the 6 hours protein consumption period. Enrichment will be quantified via tandem LC-MS/MS to derive a rate of incorporation over the 6-hour period.

  6.5 hours

Study Arms (1)

Protein + Stable Isotope Tracer Beverage

EXPERIMENTAL

Participants will consume 12 half-hourly (6 hours) isoenergetic, isonitrogenous beverages containing 0.9g/kg fat-free mass/day protein. Drinks will be enriched with stable isotopes \[2H5\]Phenylalanine and \[1-13C\]Phenylalanine, which will respectively allow for determination of muscle protein synthesis and whole-body protein synthesis over the subsequent 6 hours of feeding.

Dietary Supplement: Protein + Stable Isotope Tracer Beverage

Interventions

Protein + Stable Isotope Tracer Beverage DIETARY_SUPPLEMENT

Participants will consume 12 half-hourly (6 hours) isoenergetic, isonitrogenous beverages containing 0.9g/kg fat-free mass/day protein. Drinks will be enriched with stable isotopes \[2H5\]Phenylalanine and \[1-13C\]Phenylalanine, which will respectively allow for determination of muscle protein synthesis and whole-body protein synthesis over the subsequent 6 hours of feeding

Protein + Stable Isotope Tracer Beverage

Eligibility Criteria

• Age: 18 Years - 35 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Participants will be aged 18-35 years old
• Participants will have a BMI within the normal range (i.e., 18.5-24.9) and waist-to-hip circumference ratio of \<0.95 for males and \<0.8 for circumference for females to ensure homogeneity of the sample population
• Participants are willing to abide by the compliance rules of this study (e.g., abstain from extraneous physical activity 48h prior to session 4
• Self-reported regular menstrual cycle (25-35d) within the last 3 months (female participants)
• Physical activity score of ≥24 units as measured by the Godin leisure time exercise questionnaire

You may not qualify if:

• Inability to adhere to any of the compliance rules judged by principal investigator
• Self-reported regular tobacco or illicit drug use (e.g., growth hormone or testosterone)
• Current use of hormonal contraceptives
• Individuals with a history of allergy to local anesthetics (e.g., lidocaine)

Sponsors & Collaborators

• University of Toronto: lead

Study Sites (1)

Kinesiology & Physical Education

Toronto, Ontario, M5S 2C9, Canada

RECRUITING

MeSH Terms

Interventions

Proteins

Intervention Hierarchy (Ancestors)

Amino Acids, Peptides, and Proteins

Study Officials

• Daniel Moore, Ph.D

  University of Toronto, Faculty of KPE

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Sabrina T Barsky, Ph.D.

CONTACT

16475400115; sabrina.barsky@utoronto.ca

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: Single group: Eight healthy young (18-35 years, 4 females and 4 males) will be subjected to 2 skeletal muscle biopsies, collection of blood and urine samples, and a non-invasive 13CO2 breath-test over a 6.5-hour period while ingesting half-hourly protein beverages with stable isotope tracers. The breath-test is based on the indicator amino acid oxidation (IAAO) method.

Study Record Dates

• First Submitted: December 18, 2025
• First Posted: January 5, 2026
• Study Start: December 1, 2025
• Primary Completion: March 20, 2026
• Study Completion (Estimated): May 20, 2026
• Last Updated: January 5, 2026

Record last verified: 2025-12

Locations

CA (1)