ClinicalTrials.gov record NCT07728032

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

Record copied from ClinicalTrials.gov: Oct 10, 2026AI summaries generated: Sep 6, 2026

Impact Of A Phenylalanine-Restricted Diet On The Microbiota Composition And Metabolome Of Children With PKU

StatusRecruitingThe study is currently enrolling participants. Only the study team can say whether a particular person can join.
Study typeObservationalA study in which researchers do not assign participants to a treatment or other intervention. They observe or measure what happens, which may include study visits, tests, questionnaires or a review of medical records.
Healthy volunteersAcceptedPeople who do not have the condition being studied who are allowed to take part. Some studies include both people with the condition and healthy volunteers; others may enrol only healthy volunteers.
Age3 years old and older
SexAll
LocationUnited Kingdom
AI summaryWhat this study is about, in plain languageShow ▾Hide ▴

AI-written from the registry record, not the study's own wording. May contain errors or omissions. Check the registry text on this page and the original record ↗ before acting on it.

This observational study examines the gut microbiome and faecal metabolites in children and adolescents with phenylketonuria (PKU) and in healthy household controls. Participants are grouped by current PKU management: phenylalanine-restricted diet alone, sapropterin, or sepiapterin. Each participant provides one faecal sample and completes dietary and gastrointestinal symptom assessments.

What it is studying. Whether gut microbiota composition, microbial functional potential, and faecal metabolite profiles differ between children with PKU managed by different treatments (diet-only, sapropterin, sepiapterin) and healthy household controls.

What the researchers hope to learn. To characterise differences in gut microbiota composition, microbial genes and pathways, and faecal metabolite profiles across PKU treatment groups and controls, and to inform development of future nutritional strategies and protein substitutes for people with PKU.

What this study is about

The study's own summary, as published on ClinicalTrials.gov. Underlined terms have a short explanation.

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.

Interventions being studied

Being studied in this trial does not mean the treatment or procedure is approved or available for this condition.

Drug
  • Sapropterin Dihydrochloride
  • Sepiapterin
Other
  • Phenylalanine-restricted diet alone

Eligibility

The criteria exactly as listed on ClinicalTrials.gov. Only the study team can say whether they apply to you.

Inclusion criteria

  • Participants with PKU:
  • Aged 3-17 years.
  • Confirmed diagnosis of phenylketonuria following newborn screening.
  • Receiving ongoing clinical management for PKU.
  • For the diet-only cohort: managed with standard phenylalanine-restricted dietary treatment and not receiving sapropterin or sepiapterin.
  • For the sapropterin cohort: receiving sapropterin for at least three consecutive months and having achieved at least a 100% increase in natural protein tolerance compared with the pre-treatment prescription.
  • For the sepiapterin cohort: receiving sepiapterin for at least three consecutive months and having achieved at least a 100% increase in natural protein tolerance compared with the pre-treatment prescription.
  • Healthy household controls:
  • Aged 3 years or older.
  • Living in the same household as a participating child or adolescent with PKU.
  • No known diagnosis of PKU or another inherited metabolic disorder.

Exclusion criteria

  • Congenital malformations.
  • Chronic gastrointestinal disease.
  • Endocrine, liver, or kidney disease.
  • Other chronic medical conditions likely to affect gut microbiota composition.
  • Following a therapeutic diet for a medical condition other than PKU within the six months before stool sample collection.

Study description and what participation involves

The study's detailed description, as published on ClinicalTrials.gov.

Show the detailed description from the registry

This is a single-centre, cross-sectional observational study conducted at Birmingham Children's Hospital. The study investigates the association between phenylketonuria (PKU) treatment, degree of dietary restriction, gastrointestinal health, and the composition and functional potential of the gut microbiota. Children and adolescents aged 3-17 years with early-treated PKU are recruited into one of three cohorts according to their existing clinical management: treatment with a phenylalanine-restricted diet alone (anticipated n=30), treatment with sapropterin alongside an individualised phenylalanine-restricted diet (anticipated n=30), or treatment with sepiapterin alongside an individualised phenylalanine-restricted diet (anticipated n=14). Participants receiving sapropterin or sepiapterin have been receiving treatment for at least three months and have achieved at least a 100% increase in natural protein tolerance compared with their pre-treatment prescription. Treatment allocation, medication dosage, and dietary management are determined as part of routine clinical care and are not assigned or modified by the study. One healthy household control is recruited for each participant with PKU. Household controls are aged 3 years or older and do not have PKU or another inherited metabolic disorder. Recruiting controls from the same household aims to reduce the influence of shared environmental factors, including living conditions and food availability, when comparing gut microbiota profiles. The anticipated total enrolment is 148 participants, comprising 74 participants with PKU and 74 household controls. Each participant provides a single faecal sample. Samples are stored at -80°C and analysed using shotgun metagenomic sequencing to characterise microbial taxonomic composition, within-sample diversity, between-sample community differences, and microbial functional potential. Taxonomic profiles are assessed at multiple levels, including phylum, genus, and species. Functional annotation is used to characterise microbial genes, enzymes, and metabolic pathways. Dietary intake is assessed using a 24-hour dietary recall, including natural protein intake, protein substitute intake, dietary fibre intake, and consumption of special low-protein foods. Gastrointestinal symptoms are assessed using the age-appropriate self-report or parent-proxy version of the PedsQL Gastrointestinal Symptoms Module, and stool form is assessed using the Bristol Stool Form Scale. Relevant demographic and clinical information, including age, sex, anthropometric measurements, PKU treatment, and metabolic control, is also collected. The findings from this study may support the development of nutritional strategies and protein substitutes that more effectively promote gastrointestinal and metabolic health in individuals with PKU.

AI summaryWhat participation may involve, in plain languageShow ▾Hide ▴

AI-written from the registry record, not the study's own wording. May contain errors or omissions. Check the registry text on this page and the original record ↗ before acting on it.

Participants provide a single faecal (stool) sample that will be frozen and analysed using shotgun metagenomic sequencing and metabolite profiling to study the gut microbiome. They complete a 24-hour dietary recall about recent food and protein substitute intake, an age-appropriate gastrointestinal symptoms questionnaire (PedsQL Gastrointestinal Symptoms Module), and record usual stool form using the Bristol Stool Form Scale. Study staff also collect basic demographic and clinical information, including age, sex, height/weight (anthropometrics), current PKU treatment, and metabolic control. Healthy household controls complete the same stool sample and questionnaire assessments.

How the study is structured. A single-centre, cross-sectional observational cohort study. Children and adolescents with PKU are assigned to one of three groups based on their existing treatment (phenylalanine-restricted diet only, sapropterin, or sepiapterin); one healthy household control is recruited per participant. Each person provides a single faecal sample for shotgun metagenomic sequencing and metabolite profiling, completes a 24-hour dietary recall and the age-appropriate PedsQL Gastrointestinal Symptoms Module, and records stool form using the Bristol Stool Form Scale. Routine demographic and clinical information is also collected.

Questions you could ask

These questions are suggestions for a conversation with the study team or your own clinician, not advice.

  • This is an observational study, so the study itself gives no treatment. What would taking part involve for me, and would it change my usual care?
  • The listed sites are in United Kingdom. Is any of them reachable for me, and does the study help with travel?
  • Which of the eligibility criteria would need to be checked with tests before I could join?

More on phenylketonuria

Clinical trials38 trials listed for phenylketonuriaEvery trial the registry lists for phenylketonuria, with recruitment status, phase and sites, updated from ClinicalTrials.gov.See all trials →Research updatesWhat changed in phenylketonuria researchLatest monthly update: September 2026. Includes: Diet supply gaps. New research summarized each month in plain language, with links to every source paper.Read the latest update →

Important dates

Study start
Oct 1, 2025
Primary completion
December 2026 (estimated)
Study completion
December 2026 (estimated)
Target enrollment
148 participants (estimated)
Last updated on registry
Oct 6, 2026
Data verified
Oct 10, 2026

Sponsor and research team

The lead sponsor funds and oversees the trial. A pharmaceutical or biotech company sponsor typically means the study is testing that company's drug or device; a hospital, university, or government agency usually indicates investigator-initiated or publicly funded research.

Lead sponsor
Birmingham Women's and Children's NHS Foundation Trust
Collaborators
  • Universidade Nova de Lisboa

Central study contact

If you're interested in participating, the central contact can answer general questions about the study — including eligibility requirements and how to find a recruiting site near you. Actual eligibility is determined by the site's medical team.

Participating sites (1)

Terms used on this page · explanations by MedicalUpdates.ai

cohort
A group of people who share a characteristic, such as a diagnosis, and are studied together. 'Prospective' means they are followed forward from enrolment; 'retrospective' means existing records are reviewed.
Inclusion Criteria
The conditions a person must meet to be considered for the study, for example a confirmed diagnosis, an age range or a test result.
Exclusion Criteria
The conditions that rule a person out even if they meet the inclusion criteria, for example other illnesses, certain medicines or pregnancy.
allocation
How participants are assigned to study groups, for example at random or by a non-random rule.
enrolment
The number of participants a study plans to include, or has included. 'Estimated' means the planned number; 'actual' means the number who joined.

The study record on this page is reproduced from ClinicalTrials.gov, a database of the U.S. National Library of Medicine, where it was submitted by the study sponsor. MedicalUpdates.ai does not own this content, is not affiliated with or endorsed by ClinicalTrials.gov, NIH, or the U.S. Government, and does not verify the record. Plain-language notes, the glossary and the questions above are added by this website; text in the boxes marked "AI summary" was written by an AI model and may contain errors. Registry records change over time. Check the original record for the current version and discuss eligibility or participation with a qualified healthcare professional.

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