Safety and Efficacy of Treatment With Large Neutral Amino Acids in Patients With Classical Phenylketonuria

What this Trial Is About

Researchers are evaluating the use of large neutral amino acids (LNAAs) as a possible alternative to the standard lifelong, phenylalanine-restricted diet for adults with classical phenylketonuria (PKU). This study aims to compare LNAA treatment with the conventional diet in terms of effects on brain dopamine production, cognitive function, mental health, and safety. The research also seeks to improve understanding of PKU's underlying causes and to develop more personalized management strategies. The trial uses a randomized, open-label, crossover design where participants undergo two treatment phases of eight weeks each: one with LNAA supplementation taken three times daily using PreKUnil® LNAA medical food, and one with a low-phenylalanine diet. These are separated by a two-week washout period with a liberalized diet and no amino acid supplements. After the crossover study, participants may join an open-label extension to assess long-term safety and effectiveness. A healthy control group will also be studied to establish baseline measurements. Participants will undergo a series of assessments including dynamic PET imaging to measure brain dopamine synthesis, urine tests for neurotransmitter biomarkers, neuropsychological tests, mental health questionnaires, and monitoring for adverse events. These evaluations occur at baseline and at several points throughout the study and extension period, up to 12 months from baseline. The study will monitor adherence, safety, and changes in cognitive and mental health over time.

Effect of Large Neutral Amino Acids in Adults With Classical Phenylketonuria