Effects of Synergy on Nutrient Intake and Acceptability in Phenylketonuria (PKU)

Study Overview
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Brief Summary
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Phenylketonuria (PKU) is a rare inherited metabolic disorder, where subjects are born with a genetic deficiency in the phenylalanine hydroxylase enzyme (PAH), which leaves them unable to convert Phenylalanine (Phe) into Tyrosine (Tyr). Patients with mild PKU or partly responsive to the drug synthetic tetrahydrobiopterin (BH4) (Kuvan®) can change to a more relaxed diet. However due to difficulty to adapt their diet, these patients are at risk of an imbalanced nutritional status and an insufficient intake of specific micronutrients, essential amino acids and DHA (Docosahexaenoic acid). The study product is designed to improve the nutritional status of the patients. The study investigates if the nutritional status is indeed improved following 24 week use of the study product, and also the study aims to evaluate product acceptability.

Official Title
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An Open-label, Explorative, Post Launch, Multicenter, Multi-country Intervention Study of PKU Synergy (an Amino-acid Mixture) to Evaluate Change in Nutrient Intake in PKU Subjects With an Increased Phe-tolerance/Intake

Conditions
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Phenylketonurias

Intervention / Treatment
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* Other: PKU Synergy


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: PKU subjects identified by newborn screening and started low-Phe diet before 3 months of age PKU subjects (with or without current AAM use) with an increased Phe-tolerance/intake due to: Mild PKU phenotype BH4 treatment If treated with BH4, PKU subjects should be on a stable BH4 treatment for at least 26 consecutive weeks up to start test product intake Age≥12 years If subjects (irrespective whether BH4 users or mild PKU) use amino-acid mixture(s; AAM), then a maximum of 25 Protein Equivalents (PE) derived from the AAM per day applies and usage on a daily basis for at least 26 consecutive weeks up to Visit 1 If subjects (irrespective whether BH4 users or mild PKU) use AAMs they should be capable and willing to substitute their current AAM(s; maximum of 25 PE per day) with one portion of the test product per day If subjects (irrespective whether BH4 users or mild PKU) use omega-3, antioxidant, and/or vitamin supplements, to stop usage of the supplements and be able and willing to substitute with the test product Willing and able to comply with study procedures Willing and able to provide informed consent (and assent in case of minors if required by local law/regulations) For women of childbearing potential: not to have the intention to become pregnant during the study Exclusion Criteria: For women: Currently pregnant or lactating Current or prior use of the test product within six weeks prior to entry into the study Concurrent conditions (including renal failure and severe hepatic failure) and medication that could interfere with participation, outcome parameters or safety (as determined by Investigator) Psychotropic medication (i.e. medication affecting the nervous system) and inotropic medication Any condition creating high risk of poor compliance with study Participation in any other studies involving investigational or marketed products concomitantly or within six weeks prior to entry into the study. Except for studies related to Kuvan® (synthetic tetrahydrobiopterin (BH4)) without diagnostic, therapeutic or experimental intervention.

Ages Eligible for Study
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Minimum Age: 12 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Open label (1 arm)<br>Open label use of study product (post-marketing): PKU Synergy | Other: PKU Synergy<br>* PKU Synergy is a citrus flavored, powdered amino-acid mixture (containing traces of Phe, 4,3mg per portion; and 20 gr. Protein Equivalent (PE)) with a tailored amino acid and micronutrient profile adapted for the special requirements of HPA/PKU (Hyperphenylalaninemia/Phenylketonuria) subjects over 10 years of age with an increased Phenylalanine-(Phe) tolerance/intake.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Nutrient intake | Change in nutrient intake after 24 weeks by analysis of 3 day diet diary. Nutrients (energy, micronutrients, essential amino acids and DHA) in [(m)/(micro)gram/day] or [mg/day or mg/kg/day] | 24 weeks | 
| Product acceptability | Product acceptability questionnaire [category/score] [0-10] and [0-5] | 24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Compliance | Compliance (product consumption) using daily product intake diary [number of products used per week; per sachet of 33g] | 24 weeks | 
| Phenylalanine (Phe) levels | Dried bloodspot Phenylalanine (Phe) levels [µmol/L] | 24 weeks | 
| Blood chemistry: nutritional status | Blood chemistry: levels measured in blood: Full Fatty acid profile [For each FA Erythrocyte Membranes level (%FA)], full Amino acid profile [µmol/L], Vitamin B12 [pM], Vitamin D [ng/ml /nmol/L]; Folic acid [nM]; Selenium [µM]; Iodine [µg/L/ ng/mL]; Calcium [mg/dL]; Zinc [µmol/L]; Iron [µg/L] analyzed in blood samples by central laboratories | 24 weeks | 
| Anthropometrics: weight | Anthropometrics: Weight [kg] | 24 weeks | 
| Anthropometrics: height | Anthropometrics: Height [cm or m] | 24 weeks | 
| Anthropometrics: BMI | Anthropometrics: BMI [kg/m2], calculated from weight/height | 24 weeks |