Phe fluctuation in PKU: PKU Golike vs amino acid protein substitute
Research type
Research Study
Full title
Randomised investigation to evaluate Phe fluctuation after overnight fasting in PKU patients treated with PKU GOLIKE versus standard amino acid protein substitute
IRAS ID
303703
Contact name
Anita MacDonald
Contact email
Sponsor organisation
APR Applied Pharma Research sa
Clinicaltrials.gov Identifier
Clinicaltrials.gov Identifier
not applicable, not applicable
Duration of Study in the UK
0 years, 9 months, 31 days
Research summary
This randomised crossover study involves a previously studied and ACBS approved protein substitute for phenylketonuria (PKU). We are wanting to know if the slow-release properties of the PKU Golike will reduce overnight blood phenylalanine levels and neurotransmitters and if this in turn will alter sleep patterns. To do this we need to measure blood phenylalanine, tyrosine and branch chain amino acids (via blood spots) and take urine samples after ingestion of the protein substitute. We then want to compare this with the same parameters measured after usual amino acid protein substitutes. We aim to recruit 16 children. They will take the study product or an amino acid protein substitute for 7 days, then after a 2-week washout period they will swap for the next 7 days. In addition to the blood and urine samples, a questionnaire about sleep, a 24-hour food diary and a physical activity diary will be completed on several occasions during the study.
Results Summary:
: Background:
Physiomimic technology applied to L-amino acids (PM-AA) impacts their absorption from the gastrointestinal system slowing down their release, providing a more physiological effect. No work has been published comparing blood phenylalanine (Phe) control on PM-AA compared to free amino acids (F-AA) in patients with phenylketonuria (PKU).
Aim:
To compare the effect of PM-AA v F-AA protein substitutes on blood Phe and tyrosine (Tyr) after an overnight fast in children with classical PKU.
Methods:
Over 28 days a randomised non blinded 2 arm controlled cross over study was conducted. Patients were randomised to PM-AA or F-AAs as their last protein substitute of the day for 7 days. On the last two days of each study arm days 6 and 7 / 27 and 28 blood spots were collected at 5, 6 and 7 am measuring Phe and Tyr. A 14-day washout period separated each arm, subjects continued to take their usual protein substitute.
Results:
A total of n=13 from 16 children completed the study, mean age 11.8 y (range 7-15). There was a statistically significant difference in morning Phe concentrations in the PM-AA compared to the F-AA group when compared to baseline: PM-AA; -17.8% (p-0.048) compared to F-AAs; +27.6% (p=0.006). For Tyr there was a statistically significant increase in the PM-AA compared to baseline +33.8% (p=0.0008) while no change was noted for the F-AA. Comparing Phe and Tyr at the end of each treatment arm after completing PM-AA or F-AA a statistically significant difference was observed for Phe and Tyr, being lower after taking PM-AA v F-AA , Phe μmol/L (330.3 v 389.6) p= 0.0002 and higher for Tyr μmol/L PM-AA v F-AA (54.1 v 48.2) p-0.011.
Conclusions:
A physiomimic protein substitute given as the final substitute of the day significantly lowers blood morning Phe and increases Tyr, demonstrating improved metabolic control reducing overnight catabolism and likely muscle breakdown compared to the F-AA group.REC name
North West - Greater Manchester West Research Ethics Committee
REC reference
22/NW/0060
Date of REC Opinion
3 May 2022
REC opinion
Further Information Favourable Opinion