PhenylketonuriaNCT07728032
Impact Of A Phe-Restricted Diet On Gut Health In Children With PKU
An observational study of Phenylketonuria, run by Birmingham Women's and Children's NHS Foundation Trust at 1 site in United Kingdom.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 3 to 17 yearsHealthy volunteers can take part
- Conditions the study is for
- Phenylketonuria
- What is being tested?
- Phenylalanine-restricted diet alone, Sapropterin Dihydrochloride and Sepiapterin
- How many people
- 148 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 1 Oct 2025to Dec 2026
- Phase
- Observational
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 3 to 17 years
- All sexes
- Healthy volunteers accepted
- Child
Study population: Children and adolescents aged 3-17 years with early-treated phenylketonuria receiving clinical care at Birmingham Children's Hospital are recruited into one of three cohorts according to their current treatment: a phenylalanine-restricted diet alone, sapropterin, or sepiapterin. One healthy household control aged 3 years or older, without phenylketonuria or another inherited metabolic disorder, is recruited for each participant with phenylketonuria. All participants are enrolled according to predefined eligibility criteria.
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United Kingdom1 site, 1 recruiting
- Recruiting
Birmingham Children's Hospital
Birmingham, B4 6NH
Anita MacDonald, PhD, +44 121 333 9999, anita.macdonald@nhs.net
About this study
Official title: Impact Of A Phenylalanine-Restricted Diet On The Microbiota Composition And Metabolome Of Children With PKU
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.
Read more
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.
Read the detailed description
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.
- Conditions
- Phenylketonuria
- Being tested
- Phenylalanine-restricted diet alone, Sapropterin Dihydrochloride, Sepiapterin
- Medical subject headings
- Phenylketonurias
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Phenylalanine-restricted diet aloneOther
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 DihydrochlorideDrug
Also called Kuvan
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.
SepiapterinDrug
Also called Sephience
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 group | Role | What they receive |
|---|---|---|
| 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. Receives: Other: Phenylalanine-restricted diet alone | |
| 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. Receives: Drug: Sapropterin Dihydrochloride | |
| 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. Receives: Drug: Sepiapterin | |
| 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. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Faecal gut microbiota taxonomic composition assessed by shotgun metagenomic sequencing
Taxonomic profiles, expressed as the relative abundance of microbial taxa at phylum, genus, and species levels, are derived from shotgun metagenomic sequencing of one faecal sample per participant. Profiles are compared among participants with PKU managed by a phenylalanine-restricted diet alone, sapropterin, or sepiapterin and healthy household controls.
Measured: At enrolment (single faecal sample collection)
Secondary outcomes (6)
Faecal gut microbiota alpha diversity assessed by shotgun metagenomic sequencing
Within-sample microbial diversity is assessed from shotgun metagenomic sequencing data using alpha-diversity indices, including Shannon, Simpson, Chao1, ACE, and observed species. Alpha-diversity measures are compared across the study cohorts.
Measured: At enrolment, based on a single faecal sample
Faecal gut microbiota beta diversity assessed by shotgun metagenomic sequencing
Differences in overall microbial community composition between participants are assessed using beta-diversity measures derived from shotgun metagenomic sequencing data, including Bray-Curtis dissimilarity. Microbial community profiles are compared across the study cohorts.
Measured: At enrolment, based on a single faecal sample
Microbial functional potential assessed by shotgun metagenomic sequencing
Microbial genes and functional pathways are characterised from shotgun metagenomic sequencing data using functional annotation databases. The relative abundance of microbial genes, enzymes, and metabolic pathways is compared across the study cohorts.
Measured: At enrolment, based on a single faecal sample
Gastrointestinal symptom burden assessed using the Pediatric Quality of Life Inventory™ 3.0 Gastrointestinal Symptoms Module
Gastrointestinal symptoms are assessed using the age-appropriate version of the Pediatric Quality of Life Inventory™ 3.0 Gastrointestinal Symptoms Module. The Gastrointestinal Symptoms Total Score and individual symptom-domain scores range from 0 to 100. Higher scores indicate fewer gastrointestinal symptoms and a better outcome, whereas lower scores indicate a greater gastrointestinal symptom burden and a worse outcome. Scores are compared across the study cohorts.
Measured: At enrolment, based on a single faecal sample
Stool form assessed using the Bristol Stool Form Scale
Stool form of the collected faecal sample is classified using the Bristol Stool Form Scale, which ranges from type 1 (separate hard lumps) to type 7 (entirely liquid stool). Higher scores indicate progressively softer and looser stools; they do not inherently represent a better or worse outcome. Stool-form distributions are compared across the study cohorts.
Measured: At enrolment, based on a single faecal sample
Dietary intake assessed using a 24-hour dietary recall
Dietary intake is assessed using a 24-hour dietary recall. Nutrient and food-group measures, including natural protein intake, protein substitute intake, dietary fibre intake, and consumption of special low-protein foods, are estimated and compared across the study cohorts.
Measured: At enrolment, based on a single faecal sample
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Jul 2026
- Study start1 Oct 2025
- Primary completionDec 2026 (estimated)
- Study completionDec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for PhenylketonuriaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Cross-sectional
- Enrolment
- 148 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Birmingham Women's and Children's NHS Foundation Trust
- Sponsor type
- University, hospital or other
- Collaborators
- Universidade Nova de Lisboa
- Responsible party
- Sponsor
- Investigators
- Anita MacDonald, PhD, Principal investigator, Birmingham Children's Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07728032
- Sponsor's protocol ID
- IRAS project ID: 353831
- Status last verified
- Oct 2026
- First submitted
- 21 Jul 2026
- Last updated
- 6 Oct 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: There is no current plan to share individual participant data because the study involves a small population with a rare condition, which may increase the risk of participant identification. Any future data sharing would be subject to participant consent, ethical and institutional approvals, and an appropriate data-sharing agreement. Aggregated study results will be disseminated through scientific publications and presentations.