PKU Protein Requirements

Official title

Defining Protein Requirements in Adults With PKU: Impact of Genotype and Medical Food Intake

Overview

The objective of this research is to determine the protein requirements based on genotype and medical food consumption in a sample of adults with Phenylketonuria (PKU) using the indicator amino acid oxidation (IAAO) method.

Detailed description

Current phenylketonuria (PKU) protein guidelines are based on outdated methods and do not account for differences in genetics or how much medical formula an individual consumes. This research aims to determine more accurate and personalized protein requirements in adults with PKU that have different genetic changes using a safe and direct method called the indicator amino acid oxidation technique. The study will address two specific aims: Aim 1 will determine the protein requirements of adults with PKU that have different genetic changes and Aim 2 will investigate how the ratio of medical formula to protein intake from natural foods affects protein needs.

Adults with PKU will be recruited for this study, and vulnerable populations will not be included.

This study includes surveys, anthropometric measurements, body composition analysis, indirect calorimetry, diet history, collection of blood, urine, and expired breath samples, administration of study day diets and an oral stable isotope protocol.

Recruitment will be at Emory Genetics Clinic. Informed consent will be obtained with an in-person signature or by an electronic IRB approved signature. Participants will attend one preliminary visit and 7 study days. Each study day will last 8 hours. Participants will be enrolled for approximately 4-6 months.

Participants will have the option to bank plasma and urine samples for future use.

Interventions

• Other Nonradioactive stable oral isotope
  NaH13CO3 \[99% atom percent excess (APE) and L-\[1-13C\]Leu (99% APE) will be given orally. Isotope administration will begin with the fifth meal on each study day with each remaining meal. The nonradioactive stable oral isotope is being administered to study the physiological process of amino acid oxidation.
• Other Test diet
  Test diets will be provided on study days in 8 hourly isocaloric and isonitrogenous meals to maintain a metabolic steady state. Each meal will provide one-twelfth of the participant's daily needs to model a 12-hour fasted and 12-hour fed feeding pattern. The diet will be composed of PFD2 (Mead Johnson), Tang and Kool-Aid (Kraft), corn oil, and protein-free wheat starch cookies. Each participant will receive 1 of 7 test protein intakes (0.2-3.2 g ⋅ kg-1 ⋅ d-1) on each study day. Protein will be

Primary outcome measures

• Change in rate of oxidation of tracer in the expired breath [Time frame: Baseline, post-intervention (3-8 hours post-baseline)]

Secondary outcome measures (4)

• Change in Phenylalanine concentrations before and after provision of the oral isotope protocol to provide an assessment of phenylalanine and tyrosine metabolism following study day [Time frame: Baseline, post-intervention (8 hours post-baseline)]
• Change in Tyrosine concentrations before and after provision of the oral isotope [Time frame: Baseline, post-intervention (8 hours post-baseline)]
• Ratio of medical food protein to protein from foods protein to protein from foods [Time frame: Throughout the study (Up to 6 months post-intervention)]
• Number of participants with no adverse events related to study day diets and nonradioactive isotope tracers [Time frame: End of study (Up to 6 months post-intervention)]

Eligibility criteria

Inclusion criteria

• will be males and females (50:50) 18 years and older who were diagnosed with PKU through newborn screening or diagnosis later in life, capable of providing consent, and have previously had mutation testing

Exclusion criteria

• include concurrent illness, recent history of weight loss or acute illness during the past 6 months that could affect protein metabolism, pregnancy, lack of regular menstruation, implantable electronic devices or pacemakers, history of claustrophobia, and inability to provide consent. In addition, participants will be excluded if their genotype subgroup has already reached its predefined maximum enrollment (n=4)

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Other

Study locations

United States · 1 center

• Emory University Hospital — Atlanta

Identifiers

NCT: NCT07194993 · STUDY00009869 · 2025P012071

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗