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

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.

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.

Study Overview

• Status: Completed
• Conditions: Phenylketonurias
• Intervention / Treatment: Dietary supplement: PKU Sphere

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 15
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Germany
  • Baden-Württemberg
    • Reutlingen, Baden-Württemberg, Germany, D-72764
      • Kreiskliniken Reutlingen

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 10 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Single

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 4 Weeks; 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; 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.; Other Names: GMP; Glycomacropeptide
Experimental: 8 Weeks; 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; 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.; Other Names: GMP; Glycomacropeptide
Experimental: 12 Weeks; 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; 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.; Other Names: GMP; Glycomacropeptide

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Vitaflo International, Ltd
• Collaborators: Johannes Gutenberg University Mainz; Kreiskliniken Reutlingen
• Investigators: Principal Investigator: Peter Freisinger, Kreiskliniken Reutlingen GmbH

Study record dates

Study Major Dates

• Study Start (Actual): December 6, 2018
• Primary Completion (Actual): October 30, 2020
• Study Completion (Actual): July 31, 2023

Study Registration Dates

• First Submitted: December 7, 2018
• First Submitted That Met QC Criteria: December 10, 2018
• First Posted (Actual): December 11, 2018

Study Record Updates

• Last Update Posted (Actual): February 16, 2024
• Last Update Submitted That Met QC Criteria: February 15, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: Child; Children; Adults; Adult; Phenylketonuria; PKU; GMP; Glycomacropeptide; Amino acid mixture; Amino acid; Protein supplement; Protein substitute
• 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: MCT-W-PKUSp-2017-06-29; F-2018-043 (Other Identifier: Landesärztekammer Baden-Württemberg)

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
• product manufactured in and exported from the U.S.: No