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NCT07728032

Overview

NCT ID: NCT07728032
Lead Sponsor: Birmingham Women's and Children's NHS Foundation TrustOTHER
Official Title: Impact Of A Phenylalanine-Restricted Diet On The Microbiota Composition And Metabolome Of Children With PKU
Brief 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. 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.

Status and Timeline

Status: Recruiting
Last Update Posted: Jul 27, 2026Actual
Start Date: Oct 1, 2025Actual
Primary Completion Date: Dec 2026Estimated
Completion Date

Participation Criteria

Ages Eligible for Study: Child (0-17)
Sexes Eligible for Study: All
Accepts Healthy Volunteers?: Yes
Eligibility Criteria: 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 Plan

Study Type: Observational
Phase: No data available
Enrollment: 148Estimated
Primary Purpose: No data available
Allocation: No data available
Interventional Model: No data available
Masking: No data available

Contacts and Locations

Central Contacts: Anita MacDonald, PhDContact
anita.macdonald@nhs.net+44 121 333 9999

Similar Studies

Participant Group/Arms

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.

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.

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.

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.