Sapropterin Study
Research type
Research Study
Full title
Impact on Diet Quality and Dietary Burden of Sapropterin Dihydrochloride use in children with Phenylketonuria
IRAS ID
314071
Contact name
Anita MacDonald
Contact email
Sponsor organisation
Birmingham Women's & Children's NHS Foundation Trust
Clinicaltrials.gov Identifier
N/A, N/A
Duration of Study in the UK
3 years, 0 months, 31 days
Research summary
Summary of Research:
PKU is a rare genetic disease of the protein metabolism. Impaired transformation of the amino acid phenylalanine (Phe) into tyrosine (Tyr) leads to a build-up Phe in the blood.
Patients are diagnosed through newborn screening, and the condition is lifelong. Treatment is mainly dietetic with a low protein diet. High protein food groups such as meat, fish, eggs, milk and dairy, pulses, nuts, and some cereals are excluded. Thus, patients are prescribed medical foods – protein substitutes and special low protein foods – to help them meet their protein and energy requirements respectively. However, due to severe restrictiveness, patients and caregivers often struggle with dietary management.
Sapropterin dihydrochloride is a synthetic formulation of an intervenient in the metabolic blockage present in PKU. The drug can help about 30% of PKU patients, usually, those who present milder forms of the disease. Sapropterin allows patients to increase protein intake and/or improve their blood Phe control. It’s expected that patients under sapropterin treatment alter their food patterns due to a decrease in protein substitutes and an increase in natural food sources. This can lead to increased quality of life as well.
Therefore, we aim to study the quality of the diet and dietary burden of PKU children and parents on sapropterin treatment compared to the standard diet. This will be an observational, controlled, longitudinal, prospective study, conducted in a group of paediatric patients followed at the Birmingham Children’s Hospital. Two groups will be included – sapropterin responsive and sapropterin non-responsive patients. Questionnaires on food frequency, neophobia, and depression and anxiety will be applied to both groups and their caregivers, periodically for a period of 2 years. Outcome measurements will include anthropometric changes, metabolic control, questionnaire scores and reports.Summary of Results:
Evidence on the long-term impact of sapropterin drug treatment on dietary intake and quality of life in phenylketonuria (PKU) is limited. Understanding its effects on dietary restrictions, growth in children, and caregiver burden is essential to optimize PKU management. Methods: This prospective, two-year longitudinal study with a comparison group followed 33 children with PKU after sapropterin responsiveness assessment (21 responsive, 12 non-responsive). Outcomes included metabolic control, prescribed protein intake, dietary patterns, growth, psychological measures, and caregiver burden. Results: Sapropterin-responsive children increased natural protein intake from 10 g to 28 g/day at 2 years (p < 0.001), with reduced protein substitute intake (60 g [56–63] to 45 g [40–60], p < 0.05); no changes occurred in non-responsive children (p > 0.05). Animal-based foods (cheese, eggs, meat, fish) were introduced in 52% (11/21) of responsive children once tolerance exceeded approximately 25 g/day. The caregivers of responsive children reported reduced financial, familial-social, and personal burden (all p ≤ 0.05), alongside decreased food neophobia (p = 0.005) and caregiver depression (p = 0.013). In sapropterin-responsive children, weight and BMI z-scores remained stable, while height z-score increased over 24 months (p = 0.03); non-responsive children had higher weight and BMI z-scores than responsive children at 24 months (p = 0.037 and p = 0.026). Blood phenylalanine concentrations remained within recommended target ranges overall, with lower median values in responsive children at several time points. Conclusions: Sapropterin enabled more flexible, sustainable dietary management in responsive children with PKU, supporting metabolic control, growth, and improved family well-being and social participation. Equitable access to therapies and long-term dietetic support remain essential to optimize outcomes.REC name
Wales REC 6
REC reference
22/WA/0143
Date of REC Opinion
11 May 2022
REC opinion
Favourable Opinion