Evaluating the Efficacy and Safety of Large Neutral Amino Acids in the Treatment of Classical Phenylketonuria

Metabolic Disease Clinical Trial

Official title: Effect of Large Neutral Amino Acids in Classical Phenylketonuria

Status Not yet recruiting

Clinical Trial Summary

This research investigates the effectiveness and safety of large neutral amino acid (LNAA) supplementation in patients with classical phenylketonuria (PKU). Advanced brain imaging techniques alongside comprehensive neuropsychological and functional assessments will be employed. Short-term and long-term follow-up of participants will be conducted.

Clinical Trial Description

Standard treatment for Phenylketonuria (PKU) involves a lifelong, phenylalanine-restricted diet. Strict adherence to the diet is crucial, but often challenging. Large neutral amino acid (LNAA) supplementation is a potential alternative therapeutic approach for PKU management. The proposed mechanism involves competitive inhibition of phenylalanine (Phe) transport across the blood-brain barrier by high-dose LNAA, leading to reduced brain Phe levels. However, further investigation is needed to validate its efficacy and safety for PKU management.

Two separate crossover studies will be conducted to assess the safety and efficacy of LNAA supplementation in PKU patients.

Study 1: LNAA vs. No Treatment: This crossover trial investigates the effects of LNAA supplementation compared to no treatment. Participants will undergo both treatment phases in a randomized order:

• Phase 1: Semi-free diet with LNAA [duration: 8 weeks]

• Phase 2: Semi-free diet with no supplementation [duration: 1 week]

Study 2: LNAA vs. Phe-restricted Diet: This crossover trial compares LNAA supplementation to the current standard treatment, the Phe-restricted diet. Participants will undergo both treatment phases in a randomized order:

• Phase 1: Semi-free diet with LNAA [duration: 8 weeks]

• Phase 2: Standard Phe-restricted diet [duration: 8 weeks]

An optional open-label extension study will be offered to participants from both crossover studies. This study will assess the long-term safety and effectiveness of LNAA therapy over a period of 16 months.

A healthy control group will be recruited to obtain baseline outcome measures. Subsequently, they will be administered LNAA supplementation for a period of 1 week and then reassessed.

This project is expected to provide much-needed insights into the potential of LNAA in PKU management. The study also aims to gain a deeper understanding of the underlying pathophysiology of the disease. Finally, this work could lead to more personalized management strategies for PKU patients. ;

Related Conditions & MeSH terms

• Amino Acid Metabolism, Inborn Errors
• Brain Diseases
• Brain Diseases, Metabolic, Inborn
• Genetic Diseases, Inborn
• Metabolic Disease
• Metabolic Diseases
• Metabolism, Inborn Errors
• Phenylketonurias

• NCT number: NCT06337864
• Study type: Interventional
• Source: Rigshospitalet, Denmark
• Contact: Allan Lund, Professor, MD, DMSc
• Phone: +45 3545 1303
• Email: allan.lund@regionh.dk
• Status: Not yet recruiting
• Phase: N/A
• Start date: May 2024
• Completion date: December 2027