A Prolonged-Release Formula Has a Positive Impact on Morning Phenylalanine and Tyrosine Fluctuations in Patients with Classical Phenylketonuria (PKU)
Clinical Genetics and Therapeutics
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Primary Categories:
- Clinical- Pediatric
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Secondary Categories:
- Clinical- Pediatric
Introduction:
Fluctuations in blood phenylalanine (Phe) may be an important determinant of intellectual outcome in patients with early and continuously treated phenylketonuria (PKU). The relationship between IQ and blood Phe is clear, potentially caused by a deficit in neurotransmitter synthesis. The current study investigated the potential change in metabolic control during an overnight fast comparing the difference between a prolonged release medical formula (PKU GOLIKE) and standard of care in children with PKU.
Methods:
A 2-arm, randomized, controlled, cross-over, study in children with classical PKU was conducted. Patients were randomized to receive a prolonged-release formula as their last protein or standard of care (SoC) as their last protein for 7 days. Following a 14-day washout period, where all subjects were on their usual protein substitute, the subjects were placed into the other study arm. Baseline morning Phe and tyrosine (Tyr) concentrations were compared to morning Phe and Tyr levels following the 7-day experimental period.
Results:
Overall, 16 children, mean age 11.8 y/o (7 – 15 y/o) were recruited for the study. There was a statistically significant reduction in the morning Phe concentrations in the prolonged-release group (-17.8%, p = 0.0484 vs baseline). In contrast, there was a significant increase in morning Phe in the SoC group (+27.6%, p = 0.0063 vs baseline). Contrary to the Phe results, a significant increase of blood tyrosine (Tyr) in the prolonged-release group (+33.8%, p = 0.0008) was observed at study end. The change in Tyr for the SoC group was not significant when compared to baseline. There was a statistically significant difference between the prolonged-release group and the SoC group at the end of the treatment periods for both Phe (p = 0.0002) and Tyr (p=0.0113). No significant safety signals were observed during the study.
Conclusion:
These findings demonstrate that a prolonged release medical formula administered as the final daily protein source may improve metabolic control during the night, helping the most challenging group of patients with PKU to have improved morning Phe and Tyr control.
Fluctuations in blood phenylalanine (Phe) may be an important determinant of intellectual outcome in patients with early and continuously treated phenylketonuria (PKU). The relationship between IQ and blood Phe is clear, potentially caused by a deficit in neurotransmitter synthesis. The current study investigated the potential change in metabolic control during an overnight fast comparing the difference between a prolonged release medical formula (PKU GOLIKE) and standard of care in children with PKU.
Methods:
A 2-arm, randomized, controlled, cross-over, study in children with classical PKU was conducted. Patients were randomized to receive a prolonged-release formula as their last protein or standard of care (SoC) as their last protein for 7 days. Following a 14-day washout period, where all subjects were on their usual protein substitute, the subjects were placed into the other study arm. Baseline morning Phe and tyrosine (Tyr) concentrations were compared to morning Phe and Tyr levels following the 7-day experimental period.
Results:
Overall, 16 children, mean age 11.8 y/o (7 – 15 y/o) were recruited for the study. There was a statistically significant reduction in the morning Phe concentrations in the prolonged-release group (-17.8%, p = 0.0484 vs baseline). In contrast, there was a significant increase in morning Phe in the SoC group (+27.6%, p = 0.0063 vs baseline). Contrary to the Phe results, a significant increase of blood tyrosine (Tyr) in the prolonged-release group (+33.8%, p = 0.0008) was observed at study end. The change in Tyr for the SoC group was not significant when compared to baseline. There was a statistically significant difference between the prolonged-release group and the SoC group at the end of the treatment periods for both Phe (p = 0.0002) and Tyr (p=0.0113). No significant safety signals were observed during the study.
Conclusion:
These findings demonstrate that a prolonged release medical formula administered as the final daily protein source may improve metabolic control during the night, helping the most challenging group of patients with PKU to have improved morning Phe and Tyr control.