Effect of Large Neutral Amino Acids in Adults With Classical Phenylketonuria

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.

A randomized, open-label, crossover trial will be conducted to assess the safety and efficacy of LNAA supplementation in PKU patients. After completion of the crossover study, participants will have the option to participate in an open-label extension study aimed at evaluating the long-term safety and efficacy of LNAA.

A healthy control group will be recruited to obtain baseline outcome measures. 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.

• Urine peripheral biomarkers of neurotransmitters [Срок оценки: Crossover study: at baseline, 8, 10 and 18 weeks from baseline, Extension study: at 12 months from baseline]
• Incidence and severity of treatment-emergent adverse events (TEAEs) [Срок оценки: Baseline to week 80]
• Adult attention deficit hyperactivity disorder (ADHD) Self-Report Scale (ASRS v1.1) [Срок оценки: Crossover study: at baseline, 8, 10 and 18 weeks from baseline, Extension study: at 12 months from baseline]
• Symptom Checklist-90-Revised (SCL-90-R) [Срок оценки: Crossover study: at baseline, 8, 10 and 18 weeks from baseline, Extension study: at 12 months from baseline]
• Neuropsychological testing of flexibility and verbal fluency [Срок оценки: Crossover study: at baseline, 8, 10 and 18 weeks from baseline, Extension study: at 12 months from baseline]
• Behaviour Rating Inventory of Executive Function - Adult version (BRIEF-A) [Срок оценки: Crossover study: at baseline, 8, 10 and 18 weeks from baseline, Extension study: at 12 months from baseline]
• PKU-QOL Questionnaire Adult version [Срок оценки: Crossover study: at baseline, 8, 10 and 18 weeks from baseline, Extension study: at 12 months from baseline]
• Computerized neuropsychological testing (responses over study iPad) [Срок оценки: Crossover study: at baseline, 8, 10 and 18 weeks from baseline, Extension study: at 12 months from baseline]