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PhenylketonuriasELEMENTNCT04076176

The Effects of CGMP in Children and Adults With PKU

A study testing CGMP protein substitute and L-amino acid protein substitute in people with Phenylketonurias, run by Vitaflo International, Ltd at 3 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 4 years and older
Conditions the study is for
Phenylketonurias
What is being tested?
CGMP protein substitute and L-amino acid protein substitute
Could I receive a placebo?
No, everyone receives an active treatment
How many people
12 participants
Where
3 sitesin 2 countries
Study dates
26 Apr 2019to 31 Jan 2023
Phase
Interventional
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 4 years and older
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • 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).
Show all 15Show fewer
  • 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.

Who cannot join

  • 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.

Trial locations and contacts

3 sites in 2 countries.

3 sites in 2 countries

United Kingdom2 sites
  • Birmingham Children's Hospital

    Birmingham, West Midlands, B4 6NH

  • Bristol Royal Hospital for Children

    Bristol, Avon, BS2 8BJ

Other trials in United Kingdom

Denmark1 site
  • Rigshospitalet

    Copenhagen, 2100

Other trials in Denmark

About this study

Official title: The Effects Of Casein Glycomacropeptide On Metabolic Control And General Health Status In Children And Adults With PKU: A Randomised Crossover Trial

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.

Read the detailed description

The study is a randomised controlled trial with a crossover design conducted at several international study centres.

The study population is early and continuously treated patients with PKU that are adhering to their prescribed diet.

The participants will be given both a CGMP based protein substitute and a free AA based protein substitute as their main protein source on two different 12-week periods in a crossover design. The two periods will be separated by a 4 week wash out period.

The protein substitutes will be consumed daily together with the patient's regular low protein diet during the intervention periods.

Primary Objective The primary objective of the study is to investigate the effects of a CGMP based formula compared to an AA based formula upon mean plasma Phe levels after 12 weeks of daily intake in patients with PKU.

Secondary Objectives The secondary objectives of the study are to investigate if a CGMP based formula compared to an AA based formula in PKU patients provides any long-term health benefits concerning gut health, inflammation, oxidative stress and product acceptability.

Being tested
CGMP protein substitute, L-amino acid protein substitute
Keywords
Phenylketonuria, PKU, Child, Adult, GMP, Glycomacropeptide
Medical subject headings
Phenylketonurias

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • CGMP protein substituteDietary supplement

    Also called PKU Sphere

    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.

  • L-amino acid protein substituteDietary supplement

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

Study groups in NCT04076176
Study groupRoleWhat they receive
L-amino AcidsActive comparatorThe 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.
Receives: Dietary Supplement: L-amino acid protein substitute
PKU SphereExperimentalThe 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.
Receives: Dietary Supplement: CGMP protein substitute

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Change in overnight fasting plasma Phe

    Overnight fasting plasma phenylalanine level (μmol/l)

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

  2. Change in overnight fasting plasma Tyr

    Overnight fasting plasma tyrosine level (μmol/l)

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

  3. Change in overnight fasting blood Phe

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

    Measured: Measured twice per week up to 32 weeks

  4. Change in overnight fasting blood Tyr

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

    Measured: Measured twice per week up to 32 weeks

Secondary outcomes (54)
  1. Change in gut health: PedsQL Gastrointestinal Symptoms Scales, Version 3.0

    Five point frequency scale for each question: Never (0), Almost Never (1), Sometimes (2), Often (3), Almost Always (4).

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

  2. Change in gut health: Stool pH for reducing sugars

    From stool sample. To rule out carbohydrate intolerance as a cause of any irritable bowel syndrome symptoms

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

  3. Change in gut health: Stool calprotectin

    From stool sample

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

  4. Change in gut health: Short chain fatty acids

    From stool sample

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

  5. Change in gut health: Immunoglobulin A

    From stool sample

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

  6. Change in gut health: Bristol stool form scale

    Bristol stool form scale:

    • Type 1: Separate hard lumps, like nuts (hard to pass)
    • Type 2: Sausage-shaped, but lumpy
    • Type 3: Like a sausage but with cracks on its surface
    • Type 4: Like a sausage or snake, smooth and soft
    • Type 5: Soft blobs with clear cut edges (easy to pass)
    • Type 6: Fluffy pieces with ragged edges, a mushy stool
    • Type 7: Watery, no solid pieces, entirely liquid

    Measured: Completed for 7 days prior to days 0 (visit 2), 84 (visit 3), 112 (visit 4) and 196 (visit 5).

  7. Change in gut health: 3 day weighed diet diary

    3 day weighed diet diary

    Measured: Completed for 3 days prior to days 0 (visit 2), 84 (visit 3), 112 (visit 4) and 196 (visit 5).

  8. Change in anthropometric measurements: weight

    Weight (kg)

    Measured: Days -31 (visit 1), 0 (visit 2), 84 (visit 3), 112 (visit 4) and 196 (visit 5).

  9. Change in anthropometric measurements: height

    Height (cm)

    Measured: Days -31 (visit 1), 0 (visit 2), 84 (visit 3), 112 (visit 4) and 196 (visit 5).

  10. Change in Albumin

    Following overnight fasting

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

  11. Change in Pre-albumin

    Following overnight fasting

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

  12. Change in Transferrin

    Following overnight fasting

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

  13. Change in Retinol-binding protein

    Following overnight fasting

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

  14. Change in Glucose

    Following overnight fasting

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

  15. Change in Haemoglobin A1C

    Following overnight fasting

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

  16. Change in IGF-1

    Following overnight fasting

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

  17. Change in C-peptide

    Following overnight fasting

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

  18. Change in Short chain fatty acids

    Following overnight fasting

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

  19. Change insulin production

    Following overnight fasting

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

  20. Change in alanine

    Total plasma amino acids following overnight fasting

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

  21. Change in arginine

    Total plasma amino acids following overnight fasting

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

  22. Change in asparagine

    Total plasma amino acids following overnight fasting

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

  23. Change in citrulline

    Total plasma amino acids following overnight fasting

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

  24. Change in cystine

    Total plasma amino acids following overnight fasting

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

  25. Change in glutamate

    Total plasma amino acids following overnight fasting

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

  26. Change in glutamine

    Total plasma amino acids following overnight fasting

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

  27. Change in glycine

    Total plasma amino acids following overnight fasting

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

  28. Change in histidine

    Total plasma amino acids following overnight fasting

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

  29. Change in isoleucine

    Total plasma amino acids following overnight fasting

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

  30. Change in leucine

    Total plasma amino acids following overnight fasting

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

  31. Change in lysine

    Total plasma amino acids following overnight fasting

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

  32. Change in methionine

    Total plasma amino acids following overnight fasting

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

  33. Change in proline

    Total plasma amino acids following overnight fasting

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

  34. Change in ornithine

    Total plasma amino acids following overnight fasting

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

  35. Change in phenylalanine

    Total plasma amino acids following overnight fasting

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

  36. Change in serine

    Total plasma amino acids following overnight fasting

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

  37. Change in taurine

    Total plasma amino acids following overnight fasting

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

  38. Change in threonine

    Total plasma amino acids following overnight fasting

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

  39. Change in tryptophan

    Total plasma amino acids following overnight fasting

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

  40. Change in tyrosine

    Total plasma amino acids following overnight fasting

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

  41. Change in valine

    Total plasma amino acids following overnight fasting

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

  42. Change in renal biomarkers: Serum cystatin C

    Blood sample following overnight fasting

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

  43. Change in renal biomarkers: Serum creatinine

    Blood sample following overnight fasting

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

  44. Change in renal biomarkers: Blood urea nitrogen

    Blood sample following overnight fasting

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

  45. Change in Adiponectin

    Following overnight fasting. An anti-inflammatory marker and related with both adipose tissue and insulin sensitivity

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

  46. Change in C-reactive protein (high sensitivity measurement)

    Following overnight fasting

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

  47. Change in Serum myeloid-related protein

    Following overnight fasting

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

  48. Change in Soluble Interleukin 2 Receptor

    Following overnight fasting

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

  49. Change in Inflammatory cytokine panel

    Following overnight fasting

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

  50. Change in oxidative stress: White cells glutathione (GSH)

    Following overnight fasting

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

  51. Change in oxidative stress: Plasma thiobarbituric acid-reactive species (TBAR)

    Following overnight fasting

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

  52. Change in oxidative stress:Total antioxidant reactivity (TAR)

    Following overnight fasting

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

  53. Change in patient opinion of acceptability of the product

    Product acceptability Likert scale:

    • I loved it (5 - best)
    • I liked it (4)
    • I neither liked nor disliked it (3)
    • I didn't like it (2)
    • I really didn't like it (1 - worst)

    Measured: Days 84 (visit 3) and 196 (visit 5)

  54. Change in hunger

    Measuring hunger in primary school children Likert scale:

    • I am really hungry! My belly feels very empty and is rumbling! (1 - worst)
    • I am quite hungry and my belly feels a little empty. (2)
    • I feel just right, not too hungry and not too full. (3)
    • I am quite full, but there is still a little room in my belly. (4)
    • I am not hungry at all! My belly feels very full and I cannot eat any more food! (5 - best)

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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted3 Sep 2019
  2. Study start26 Apr 2019
  3. Primary completion31 Jan 2023
  4. Study completion31 Jan 2023

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase N/A
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Crossover
Masking
None (open label)
Enrolment
12 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04076176
Sponsor's protocol ID
MCT-CGMP-2017-05-23
Other IDs
239520, 19/NW/0032
Acronym
ELEMENT
Status last verified
Aug 2025
First submitted
30 May 2019
Last updated
20 Aug 2025
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • 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.

    PubMed 39579672

Questions about this trial

What is this clinical trial studying?

A study testing CGMP protein substitute and L-amino acid protein substitute in people with Phenylketonurias, run by Vitaflo International, Ltd at 3 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 15 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 20 Aug 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites in United Kingdom, Denmark. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change in overnight fasting plasma Phe (time frame: Measured at days 0 (visit 2), 84 (visit 3), 112 (visit 4) and 196 (visit 5)). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04076176, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Aug 2025.

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