Impact Of A Phe-Restricted Diet On Gut Health In Children With PKU
ConditionPhenylketonuria
Trial statusRecruiting
Trial phaseNot listed
Trial typeObservational
Biological sexAll
Age3-17
SponsorBirmingham Women's and Children's NHS Foundation Trust
About this trial
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.
Eligibility criteria
This trial accepts healthy volunteersQualifiers
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.
Disqualifiers
Congenital malformations.
Chronic gastrointestinal disease.
Endocrine, liver, or kidney disease.
Other chronic medical conditions likely to affect gut microbiota composition.
Trial 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.
Trial design
Design model
Cohort
Time perspective
Cross-sectional
Treatments tested in this trial
Phenylalanine-restricted diet alone
Other interventionParticipants 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
DrugParticipants 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
DrugParticipants 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.
Treatment groups
148 Participants
are divided into 4 treatment groupsGroup A: PKU - Diet Only1 intervention
Group B: PKU - Sapropterin1 intervention
Group C: PKU - Sepiapterin1 intervention
Group D: Healthy Household Controls0 interventions
Trial outcomes
Primary outcomes
1
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.
Time frame
At enrolment (single faecal sample collection)Secondary outcomes
1
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.
Time frame
At enrolment, based on a single faecal sample2
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.
Time frame
At enrolment, based on a single faecal sample3
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.
Time frame
At enrolment, based on a single faecal sample4
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.
Time frame
At enrolment, based on a single faecal sampleSponsors and contacts
Click on the lead sponsor to view all of their trials.
Birmingham Women's and Children's NHS Foundation Trust
Lead sponsor
Universidade Nova de Lisboa
Collaborator
Source ClinicalTrials.gov