Evaluation of Low Phenylalanine Formulas

The Effects of an Innovative Glycomacropeptide Based Protein Supplement Purified to Lower the Phenylalanine Content for the Treatment of Paediatric Patients With Phenylketonuria

Ajinomoto Cambrooke has developed a PKU protein substitute that is a proprietary blend of purified Glycomacropeptide (GMP) and essential amino acids, under the brand name Glytactin®. One serving of such Glytactin® products contains 20mg or less of Phenylalanine (Phe). The aim of the proposed study is to use this purified GMP-AA-based protein substitute, with less Phe per gram of protein equivalent than other commercially available products, in children with PKU at 100% of their protein substitute intake and evaluate its efficacy and the change in blood Phe in comparison to Phe-free L-AA-based protein substitutes.

Study Overview

• Status: Active, not recruiting
• Conditions: Phenylketonurias
• Intervention / Treatment: Dietary supplement: Glytactin; Dietary supplement: L-AA

Detailed Description

Study Design This is a 2-stage, 15-week randomized crossover trial. The randomized crossover design was chosen as it reduces the influence of differences among individuals; and it offers statistical efficiency (requires fewer subjects than non-crossover designs).

In summary, 2 groups of 9 participants each will be assigned to either (1) sequence 1: take GMP-AA-based PS for the first 4 weeks and then take only L-AA-based Protein Substitute for 4 weeks, or (2) take only L-AA-based Protein Substitute for the first 4 weeks and then take GMP-AA-based PS for 4 weeks. At the end of the first 4 weeks, a 2-week washout period will follow with both groups only consuming L-AA-based PS. Randomization will be generated by a block randomization system and the random order will be kept within a sealed envelope.

Primary research objective The principal research objective of this study is to evaluate the effect on Phe levels of a low-Phe diet combined with a purified GMP-AA-based protein substitute (containing 1 mg Phe/g Protein Equivalent), in the treatment of paediatric patients with PKU.

Secondary research objectives The secondary objectives of the study aim to investigate whether there are any differences between the GMP-AA-based protein substitute and L-AA-based protein Substitute in the frequency and quantity of protein substitute intake, if any GI (gastrointestinal) symptoms occur with ingestion of the GMP-AA-based protein substitute, effect on satiety (hunger) and mood and any differences in anthropometric data.

• Study Type: Interventional
• Enrollment (Estimated): 19
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United Kingdom
  • London, United Kingdom, WC1N 3JH
    • Great Ormond Street Hospital for Children
  • West Midlands
    • Birmingham, West Midlands, United Kingdom, B4 6NH
      • Birmingham Women and Children's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patients with PKU, aged 5 to 16 years of age, currently compliant with protein restricted diet and L-AA- and/or GMP-AA-based protein substitute willing to switch to a GMP-AA-based only product for 4 weeks.

  • 2 out of 4 last blood Phe levels within target range (i.e. 50%): Target range 120-360µmol/l <12 years Target range 120-600µmol/l >12 years

Exclusion Criteria:

• • Milk protein allergy

  • Pregnancy
  • Severe medical diagnosis not related to PKU
  • Treatment with Sapropterin hydrochloride (KUVAN)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Sequence AB: GMP-AA -> L-AA; After an initial washout period of 2 weeks, participants randomised to Sequence AB will consume GMP-AA for 3 months whilst keeping a food diary and sending blood spots for twice weekly analysis. At the end of 3 months there is a further 2 week washout period with L-AA, after which the participant will consume L-AA for 3 months whilst keeping a food diary and sending blood spots for twice weekly analysis.	Dietary supplement: Glytactin; Glycomacropeptide based protein substitute for dietary treatment of PKU; Other Names: Glytactin Build 20 Flavours; Glytactin Ready To Drink (RTD) 15 Lite; Glytactin Build 10
Placebo Comparator: Sequence BA: L-AA -> GMP-AA; After an initial washout period of 2 weeks, participants randomised to Sequence BA will consume L-AA for 3 months whilst keeping a food diary and sending blood spots for twice weekly analysis. At the end of 3 months there is a further 2 week washout period with L-AA, after which the participant will consume GMP-AA for 3 months whilst keeping a food diary and sending blood spots for twice weekly analysis.	Dietary supplement: L-AA; Amino acid based protein substitute for dietary treatment of PKU

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in blood Phe in	Change in blood Phe in subjects ingesting purified GMP-AA-protein substitute compared with the change when ingesting L-AA-protein substitute	16 weeks

Collaborators and Investigators

• Sponsor: Ajinomoto Co., Inc.
• Collaborators: Great Ormond Street Hospital for Children NHS Foundation Trust; Birmingham Children's Hospital
• Investigators: Principal Investigator: Anita MacDonald, BSc PhD, Birmingham Women and Children's Hospital

Study record dates

Study Major Dates

• Study Start (Actual): January 30, 2023
• Primary Completion (Estimated): January 1, 2025
• Study Completion (Estimated): April 1, 2025

Study Registration Dates

• First Submitted: March 20, 2024
• First Submitted That Met QC Criteria: March 25, 2024
• First Posted (Actual): March 27, 2024

Study Record Updates

• Last Update Posted (Estimated): April 15, 2024
• Last Update Submitted That Met QC Criteria: April 12, 2024
• Last Verified: April 1, 2024

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: CUK001

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