A 16 Week Study Evaluating the Introduction of a GMP Based Protein Substitute in Participants With PKU

Study Overview
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Brief Summary
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This study aims to measure changes in participants' blood phenylalanine (Phe) levels in participants with PKU when switching from a conventional amino acid based protein substitute to a GMP based protein substitute (PKU Sphere) over a 16 week period.

Detailed Description
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This is a stepped wedge, open-label study of PKU Sphere for the dietary management of participants with Phenylketonuria. It will be carried out with 33 participants who will be randomised into one of three clusters. The total study length per patient is 16 weeks. Each cluster transitions from taking their standard amino acid product alone to incorporating PKU Sphere (at least 50% of their protein substitue requirement) at different timepoints: week 5, 9 or 13. Participants will have a face-to-face clinical review at the time of recruitment (week 0) and at 16 weeks (completion of the study). They will also have an additional telephone review when they switch onto PKU Sphere. Blood samples will be taken at baseline, and then every two weeks for the duration of the study. In addition to these study visits and procedures, routine clinical care will continue in line with local guidelines.

Official Title
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Multicentre Study Project to Evaluate the New Generation of Protein Supplements With Glycomacropeptide (GMP) in Patients With Phenylketonuria (PKU) Aged 10 Years and Older Over a 16 Week Period.

Conditions
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Phenylketonurias

Intervention / Treatment
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* Dietary Supplement: PKU Sphere


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of PKU made in neonatal period Treated by a low-phenylalanine diet and necessity of intake of at least one protein substitute per day Aged 10 years and above Three blood Phe measurements taken within the preceding six months Willing to replace current amino acid based protein substitute with PKU Sphere Ability to take at least 50% of protein requirements as PKU Sphere Ability to comply with the study protocol, in the opinion of the investigator Willingly given, written, informed consent from patient or parent/guardian Willingly given, written assent (if appropriate) Exclusion Criteria: Women who are pregnant or planning to become pregnant during the study period Participants with atypical PKU (e.g. BH4 deficient) Intake of sapropterin dihydrochloride (Kuvan) in the six weeks prior to recruitment in the study Patients with soya, milk or fish allergies Any other severe disease

Ages Eligible for Study
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Minimum Age: 10 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: The study has a stepped wedge design, which is chosen over the alternative cross-over study as it allows that all participants start on the amino acid supplement and avoids the difficulty of the 'wash-out' period being the same as one of the treatment strategies being offered.
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 4 Weeks<br>All patients randomised to this arm will start on an amino acid based protein substitute and they will all swtich over to incorprating PKU Sphere after 4 weeks. | Dietary Supplement: PKU Sphere<br>* PKU sphere is a powdered, low phenylalanine protein substitute containing a balanced mix of casein glycomacropeptide (GMP) isolate, essential and non-essential amino acids, carbohydrate, vitamins, minerals and docosahexaenoic acid (DHA). With sugar and sweetener.<br>* Other names: Glycomacropeptide;|
| Experimental: 8 Weeks<br>All patients randomised to this arm will start on an amino acid based protein substitute and they will all swtich over to incorprating PKU Sphere after 8 weeks. | Dietary Supplement: PKU Sphere<br>* PKU sphere is a powdered, low phenylalanine protein substitute containing a balanced mix of casein glycomacropeptide (GMP) isolate, essential and non-essential amino acids, carbohydrate, vitamins, minerals and docosahexaenoic acid (DHA). With sugar and sweetener.<br>* Other names: Glycomacropeptide;|
| Experimental: 12 Weeks<br>All patients randomised to this arm will start on an amino acid based protein substitute and they will all swtich over to incorprating PKU Sphere after 12 weeks. | Dietary Supplement: PKU Sphere<br>* PKU sphere is a powdered, low phenylalanine protein substitute containing a balanced mix of casein glycomacropeptide (GMP) isolate, essential and non-essential amino acids, carbohydrate, vitamins, minerals and docosahexaenoic acid (DHA). With sugar and sweetener.<br>* Other names: Glycomacropeptide;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in blood Phe | Change in blood Phe concentrations when switching from an amino acid based protein substitute to a GMP based one (PKU Sphere). A minimum of five (5) blood samples (including a baseline measurement and one from each treatment arm) will be required for a patient to be included in the final analysis. | Baseline (week 0) and weeks 2, 4, 6, 8, 10, 12, 14 and 16. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in blood tyrosine | Impact of a GMP based protein substitute on blood tyrosine levels. A minimum of five (5) blood samples (including a baseline measurement and one from each treatment arm) will be required for a patient to be included in the final analysis. | Baseline (week 0) and weeks 2, 4, 6, 8, 10, 12, 14 and 16. | 
| Dietary intake | Compliance with a low protein diet - 3-day food diary. | Weeks 1 and 16. | 
| Protein substitute intake | Compliance with the recommended volume of protein substitute - 3-day protein substitute diary. | Weeks 1, 4, 8, 12 and 16 | 
| Stool patterns | 3-day diary noting stool type (Bristol stool chart). | Weeks 1, 4, 8, 12 and 16 | 
| Satiety questionnaire | Short questionnaire asking participants to consider their satiety levels over the last 7 days, asking them if it has increased, stayed the same or decreased. Questionnaire validated as part of a bachelor thesis. | Weeks 1, 4, 8, 12 and 16 | 
| Acceptance questionnaire | Questionnaire to collect information about taste, odour and practicability of the protein substitutes. The questions are answered on a scale of 1 (bad) to 5 or 6 (good). Questionnaire validated as part of a bachelor thesis. | Weeks 1, 4, 8, 12 and 16 | 
| Gastrointestinal symptoms questionnaire | Short questionnaire asking participants to consider their general gastrointestinal health over the previous 7 days. The occurrence of various GI symptoms are given as never, rare, often or always. Questionnaire validated as part of a bachelor thesis. | Weeks 1, 4, 8, 12 and 16 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Phenylketonuria, PKU, Child, Children, Adult, Adults, GMP, Glycomacropeptide, Amino acid mixture, Amino acid, Protein supplement, Protein substitute