The Effects of CGMP in Children and Adults With PKU

NCT04076176 | Completed

• 3 other identifiers: MCT-CGMP-2017-05-2323952019/NW/0032
• Study Type: interventional
• Target: 12
• Locations: 2 countries
• Sites: 3

Brief Summary

Randomised controlled trial with a crossover design. For early and continuously treated patients with phenylketonuria (PKU) that are adherent. Two 12-week periods where patients consume either casein glycomacropeptide (CGMP) based protein substitute or a free amino acid (AA) based protein substitute. 4 week wash out period in between. The protein substitutes will be consumed daily together with the patient's regular low protein diet.

Conditions

Phenylketonurias

Keywords

Phenylketonuria; PKU; Child; Adult; GMP; Glycomacropeptide

Outcome Measures

Primary Outcomes (4)

• Change in overnight fasting plasma Phe

  Overnight fasting plasma phenylalanine level (μmol/l)

  Measured at days 0 (visit 2), 84 (visit 3), 112 (visit 4) and 196 (visit 5)

• Change in overnight fasting plasma Tyr

  Overnight fasting plasma tyrosine level (μmol/l)

  Measured at days 0 (visit 2), 84 (visit 3), 112 (visit 4) and 196 (visit 5)

• Change in overnight fasting blood Phe

  Overnight fasting blood phenylalanine level (μmol/l) using blood spots

  Measured twice per week up to 32 weeks

• Change in overnight fasting blood Tyr

  Overnight fasting blood tyrosine level (μmol/l) using blood spots

  Measured twice per week up to 32 weeks

Secondary Outcomes (54)

• Change in gut health: PedsQL Gastrointestinal Symptoms Scales, Version 3.0

  Days 0 (visit 2), 84 (visit 3), 112 (visit 4) and 196 (visit 5).

• Change in gut health: Stool pH for reducing sugars

  Days 0 (visit 2), 84 (visit 3), 112 (visit 4) and 196 (visit 5).

• Change in gut health: Stool calprotectin

  Days 0 (visit 2), 84 (visit 3), 112 (visit 4) and 196 (visit 5).

• Change in gut health: Short chain fatty acids

  Days 0 (visit 2), 84 (visit 3), 112 (visit 4) and 196 (visit 5).

• Change in gut health: Immunoglobulin A

  Days 0 (visit 2), 84 (visit 3), 112 (visit 4) and 196 (visit 5).

Study Arms (2)

L-amino Acids

ACTIVE COMPARATOR

The specific amount and timing of L-amino acid consumption will be at the instruction of a dietitian following a review of the individual patient's dietary needs. Consumption period: 12 weeks.

Dietary Supplement: L-amino acid protein substitute

PKU Sphere

EXPERIMENTAL

The specific amount and timing of PKU sphere consumption will be at the instruction of a dietitian following a review of the individual patient's dietary needs. Consumption period: 12 weeks.

Dietary Supplement: CGMP protein substitute

Interventions

CGMP protein substitute DIETARY_SUPPLEMENT

PKU sphere is a powdered, low phenylalanine protein substitute, containing a balanced mix of casein glycomacropeptide (CGMP) isolate, essential and non-essential amino acids, carbohydrate, vitamins, minerals, trace elements and the omega-3 long chain polyunsaturated fatty acid (LCP); docosahexaenoic acid.

Also known as: PKU Sphere

PKU Sphere

L-amino acid protein substitute DIETARY_SUPPLEMENT

Patient may choose from a list of products, specified in the protocol, that are nutritionally comparable to PKU Sphere.

L-amino Acids

Eligibility Criteria

• Age: 4 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• PKU patient diagnosed on newborn screening (NBS).
• \> 50% of protein intake from protein substitutes.
• (CHILDREN) Dietary intake of ≤ 1000 mg Phe from natural protein or ≤20 g natural protein inclusive of fruit and vegetables per day.
• (ADULTS) Dietary intake of ≤ 1500 mg Phe from natural protein or ≤ 30 g natural protein inclusive of fruit and vegetables per day.
• (CHILDREN) Three out of the last four consecutive Phe measurements within the target range (≤360 µmol/L in patients aged 4-12 years).
• (ADULTS) Two out of the last four consecutive Phe measurements within the target range (≤600 µmol/L for adults).
• Male or female aged 4-12 years or 18 years and over.
• Early and continuously treated. Adherent to their prescribed PKU diet consisting of a protein-restricted diet and free AA based protein substitute.
• Otherwise in good general health as evidenced by medical history.
• Able to provide written informed consent (patient or parent/guardian).
• Able to comply with the study protocol and take study product according to the opinion of the PI.
• Protein substitute intake provided by L-amino acid supplements only.
• (ADULTS) No studies have been done in pregnant women. To ensure patients safety, female patients of childbearing potential must have a negative pregnancy test prior to completing the screening procedures.
• (ADULTS) All female patients of childbearing potential and sexually mature males should be willing to use a medically accepted method of contraception throughout the study.
• Successful 3-day PKU Sphere taste test.

You may not qualify if:

• Concomitant diseases / disorders such as but not limited to renal or gut disease / disorders and diabetes.
• Currently or previously treated with tetrahydrobiopterin (BH4), pegylated recombinant phenylalanine ammonia lyase (PEG PAL), large neutral amino acids.
• Previous intake of CGMP for more than four consecutive weeks.
• Having a current infection.
• Known soya, milk or fish allergies / intolerance.
• Patients who are currently participating in, plan to participate in, or have participated in an interventional investigational drug, food or medical device trial within 30 days prior to screening visit.
• Where applicable, patients not covered by Health Insurance System and/or not in compliance with the recommendations of National Law in force.

Sponsors & Collaborators

• Vitaflo International, Ltd: lead
• Arla Foods: collaborator

Study Sites (3)

Rigshospitalet

Copenhagen, 2100, Denmark

Location

Bristol Royal Hospital for Children

Bristol, Avon, BS2 8BJ, United Kingdom

Location

Birmingham Children's Hospital

Birmingham, West Midlands, B4 6NH, United Kingdom

Location

Related Publications (1)

• Pinto A, Daly A, Newby C, Robotham A, Heales S, Eaton S, Aitkenhead H, Gilmour K, Jackson R, Ashmore C, Evans S, Rocha JC, Ilgaz F, Hickson M, MacDonald A. The effects of casein glycomacropeptide on general health status in children with PKU: A randomized crossover trial. Mol Genet Metab. 2024 Dec;143(4):108607. doi: 10.1016/j.ymgme.2024.108607. Epub 2024 Nov 4.

  PMID: 39579672 RESULT

MeSH Terms

Conditions

Phenylketonurias

Condition Hierarchy (Ancestors)

Brain Diseases, Metabolic, Inborn; Brain Diseases, Metabolic; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Amino Acid Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Officials

• Anita MacDonald

  Birmingham Women's and Children's NHS Foundation Trust

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 30, 2019
• First Posted: September 3, 2019
• Study Start: April 26, 2019
• Primary Completion: January 31, 2023
• Study Completion: January 31, 2023
• Last Updated: August 20, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

DK (1); GB (2)