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

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

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.

Study Overview

• Status: Completed
• Conditions: Phenylketonurias
• Intervention / Treatment: Other: PKU Synergy

• Study Type: Interventional
• Enrollment (Actual): 13
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Germany
  • Leipzig, Germany
    • University Hospital Leipzig
  • Münster, Germany
    • University Hospital Münster
• Netherlands
  • Groningen, Netherlands
    • University Medical Center Groningen (UMCG)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion criteria:

1. PKU subjects identified by newborn screening and started low-Phe diet before 3 months of age

2. PKU subjects (with or without current AAM use) with an increased Phe-tolerance/intake due to:

   • Mild PKU phenotype
   • BH4 treatment
3. 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
4. Age≥12 years
5. 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
6. 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
7. 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
8. Willing and able to comply with study procedures
9. Willing and able to provide informed consent (and assent in case of minors if required by local law/regulations)
10. For women of childbearing potential: not to have the intention to become pregnant during the study

Exclusion Criteria:

1. For women: Currently pregnant or lactating
2. Current or prior use of the test product within six weeks prior to entry into the study
3. Concurrent conditions (including renal failure and severe hepatic failure) and medication that could interfere with participation, outcome parameters or safety (as determined by Investigator)
4. Psychotropic medication (i.e. medication affecting the nervous system) and inotropic medication
5. Any condition creating high risk of poor compliance with study
6. 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Open label (1 arm); Open label use of study product (post-marketing): PKU Synergy	Other: PKU Synergy; 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.

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety Parameters (Incidence, frequency, seriousness, severity and relatedness of (Serious) Adverse Events)	Incidence, frequency, seriousness, severity and relatedness of (Serious) Adverse Events	24 weeks
Tolerance (Standard gastrointestinal questionnaire reporting)	Tolerance: Standard gastrointestinal questionnaire reporting of diarrhea constipation, abdominal distension, nausea, vomiting, burping, flatulence, regurgitation, and colic/cramps (0, 1, 12 and 24 weeks) [absent, mild, moderate, severe]	24 weeks
Subject characteristics	Age [years]; Sex [male/female]; Country [Germany/Netherlands]	week 0
Phe tolerance level and/or range	[mg Phe/day]	week 0
PKU phenotype	Recording of PKU (Phenylketonuria) genotype from medical history [hyperphenylalaninemia (HPA) or mild/moderate/classic PKU]	week 0

Collaborators and Investigators

• Sponsor: Nutricia Research

Study record dates

Study Major Dates

• Study Start (Actual): June 26, 2019
• Primary Completion (Actual): May 27, 2021
• Study Completion (Actual): May 27, 2021

Study Registration Dates

• First Submitted: November 19, 2018
• First Submitted That Met QC Criteria: December 14, 2018
• First Posted (Actual): December 17, 2018

Study Record Updates

• Last Update Posted (Actual): December 9, 2021
• Last Update Submitted That Met QC Criteria: December 8, 2021
• Last Verified: December 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Metabolic Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Genetic Diseases, Inborn; Metabolism, Inborn Errors; Brain Diseases, Metabolic; Brain Diseases, Metabolic, Inborn; Amino Acid Metabolism, Inborn Errors; Phenylketonurias
• Other Study ID Numbers: MPR16TA09791

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No