Impact Of A Phe-Restricted Diet On Gut Health In Children With PKU

Sponsor
Birmingham Women's and Children's NHS Foundation Trust
Study ID
NCT07728032
Status
Recruiting
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Conditions

Eligibility Criteria

Sex
ALL
Age
3 Years - 17 Years
Healthy Volunteers
Accepted

Interventions

  • Phenylalanine-restricted diet alone — OTHER
    Participants are managed with a phenylalanine-restricted diet and prescribed protein substitutes as part of their usual clinical care. They are not receiving sapropterin or sepiapterin. Dietary treatment is not assigned or modified by this observational study.
  • Sapropterin Dihydrochloride — DRUG
    Participants receive sapropterin as part of their usual clinical care, alongside an individualised phenylalanine-restricted diet. Sapropterin treatment and dosage are prescribed independently of this observational study and are not assigned or modified by the investigators.
  • Sepiapterin — DRUG
    Participants receive sepiapterin as part of their existing clinical management, alongside an individualised phenylalanine-restricted diet. Sepiapterin treatment and dosage are determined independently of this observational study and are not assigned or modified by the investigators.

Study Details

Phenylketonuria (PKU) is an inherited disorder of phenylalanine (Phe) metabolism. The mainstay of treatment is a Phe-restricted diet, which aims to maintain blood Phe concentrations within the recommended range and prevent neurological complications. Some individuals with PKU respond to pharmacological treatments, including sapropterin, a synthetic form of tetrahydrobiopterin (BH4), or sepiapterin. These treatments may increase Phe tolerance and allow a less restrictive diet. Diet is an important determinant of gut microbiota composition and function. However, the effects of the Phe-restricted diet and pharmacologically enabled dietary relaxation on the gut microbiota in PKU remain poorly understood. This observational study includes children and adolescents with PKU aged 3-17 years attending Birmingham Children's Hospital. Participants include those managed exclusively with a Phe-restricted diet, those receiving sapropterin, and those receiving sepiapterin. One healthy household control is recruited for each participant with PKU. Faecal samples are collected for shotgun metagenomic sequencing and metabolite profiling. Dietary intake, gastrointestinal symptoms, stool characteristics, clinical information, and PKU treatment are also assessed. The study investigates whether gut microbiota composition, microbial functional potential, and faecal metabolite profiles differ between participants managed with a Phe-restricted diet, those receiving pharmacological treatment, and healthy household controls. The findings may improve understanding of the relationships between PKU treatment, dietary restriction, gastrointestinal health, and the gut microbiome and may inform future nutritional strategies for individuals with PKU.

Key Dates

First listed
Jul 27, 2026
Start date
Oct 1, 2025
Status verified
Jul 2026
Primary completion
Dec 31, 2026
Completion
Dec 31, 2026

Study Design

Enrollment
148 participants (estimated)

Arms

  • Arm: PKU - Diet Only
    Children and adolescents aged 3-17 years with early-treated phenylketonuria who are managed exclusively with a phenylalanine-restricted diet and are not receiving sapropterin or sepiapterin. Participants provide a faecal sample and undergo dietary, clinical, gastrointestinal symptom, and stool assessments.
  • Arm: PKU - Sapropterin
    Children and adolescents aged 3-17 years with early-treated phenylketonuria who have been receiving sapropterin for at least 3 months and have achieved at least a 100% increase in natural protein tolerance compared with before treatment. Sapropterin treatment is not assigned as part of this observational study. Participants provide a faecal sample and undergo dietary, clinical, gastrointestinal symptom, and stool assessments.
  • Arm: PKU - Sepiapterin
    Children and adolescents aged 3-17 years with early-treated phenylketonuria who have been receiving sepiapterin for at least 3 months and have achieved at least a 100% increase in natural protein tolerance compared with before treatment. Sepiapterin treatment is not assigned as part of this observational study. Participants provide a faecal sample and undergo dietary, clinical, gastrointestinal symptom, and stool assessments.
  • Arm: Healthy Household Controls
    Healthy household members without phenylketonuria who are recruited at a ratio of one control for each participant with phenylketonuria. Controls provide a faecal sample and complete the relevant dietary, gastrointestinal symptom, and stool assessments.

Primary Outcome Measure

Faecal gut microbiota taxonomic composition assessed by shotgun metagenomic sequencing [ Time Frame: At enrolment (single faecal sample collection) ]

Central Contacts

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