Liquid valine and isoleucine for MSUD
Research type
Research Study
Full title
Valine 50mg/ml and isoleucine 25mg/ml oral solutions for Maple Syrup Urine Disease (MSUD) – Acceptability and Tolerance Study
IRAS ID
324480
Contact name
Anita MacDonald
Contact email
Sponsor organisation
Meta Healthcare Ltd
Clinicaltrials.gov Identifier
Clinicaltrials.gov Identifier
N/A, N/A
Duration of Study in the UK
2 years, 0 months, 1 days
Research summary
Research Summary:
This is a prospective, open label, observational market research study in 5 children with Maple Syrup Urine Disease (MSUD). People with MSUD need to take a valine and isoleucine supplement daily as part of their treatment. Patients who are currently taking a powdered valine and isoleucine supplement for MSUD will be recruited for a 56 day trial, of a new ready-to-use liquid valine supplement and a new ready-to-use liquid isoleucine supplement, to evaluate the tolerability and acceptability of the study products compared with their usual products. Subjects will replace their usual daily dose of powdered valine supplement with the equivalent amount of the liquid valine supplement for 28 days and then replace their usual daily dose of powdered isoleucine supplement with the equivalent amount of the liquid isoleucine supplement for a futher 28 days. Gastrointestinal tolerance, acceptability and adherence data will be collected along with routine blood results for valine, leucine and isoleucine. 3-day food diaries will collect data on valine and isoleucine intake from food during the study. The outcome of this assessment will be used in a submission to regulatory authorities to enable the study products to be made reimbursable on prescription in the UK.Summary of Results:
Introduction: Maple Syrup Urine Disease (MSUD) is a rare metabolic disorder requiring lifelong restriction of branched-chain amino acids (BCAA), and targeted supplementation with valine (Val) and isoleucine (Ile) to maintain metabolic stability. Traditionally, powdered Val and Ile supplements are prescribed. New ready-to-use (RTU) liquid formulations of Val and Ile are developed that aim to improve ease of use and patient experience. This study aimed to assess the efficacy, acceptability, and tolerability of RTU Val and Ile supplements in children with classical MSUD.
Methods: A prospective, open-label, observational study was conducted in 5 pediatric patients with classical MSUD over 56 days. In Phase 1 (Days 0–28), participants received the new Val RTU liquid formulation, while continuing their usual powdered Ile supplement. In Phase 2 (Days 29–56), participants returned to powdered Val and changed to the RTU liquid Ile supplement. Weekly plasma BCAA’s were monitored. Acceptability, gastrointestinal tolerance, adherence, and dietary intake were assessed through questionnaires and food diaries.
Results: RTU Val and Ile supplements were well tolerated and accepted by all participants. Plasma Leu decreased with the RTU Val (mean 253 µmol/L) and RTU Ile (mean 234 µmol/L) phases compared to baseline (mean 356 µmol/L). Required doses of Val and Ile decreased by 30% and 18.4%, respectively, suggesting improved adherence or enhanced efficacy. Palatability and ease of use were rated more favourably for RTU products, with no adverse effects or adherence issues reported. Dietary intake remained stable throughout the study.
Discussion: RTU Val and Ile supplements demonstrated promising outcomes in terms of metabolic control, adherence, and patient/caregiver satisfaction. The reduction in plasma Leu and supplement dosage points to potential clinical advantages. While findings are limited by small sample size and short follow-up, RTU formulations appear to offer a practical and patient-centered alternative to powdered Val and Ile supplements. Further studies are needed to confirm long-term benefits in larger, more diverse cohorts.REC name
West Midlands - South Birmingham Research Ethics Committee
REC reference
24/WM/0171
Date of REC Opinion
3 Sep 2024
REC opinion
Favourable Opinion