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.
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
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.
- Conditions
- Phenylketonurias
- 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 group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Dietary Supplement: CGMP protein substitute |
What is being measured
The primary outcome is the main question the study is designed to answer.
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)
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)
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
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)
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).
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).
Change in gut health: Stool calprotectin
From stool sample
Measured: Days 0 (visit 2), 84 (visit 3), 112 (visit 4) and 196 (visit 5).
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).
Change in gut health: Immunoglobulin A
From stool sample
Measured: Days 0 (visit 2), 84 (visit 3), 112 (visit 4) and 196 (visit 5).
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).
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).
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).
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).
Change in Albumin
Following overnight fasting
Measured: Days 0 (visit 2), 84 (visit 3), 112 (visit 4) and 196 (visit 5).
Change in Pre-albumin
Following overnight fasting
Measured: Days 0 (visit 2), 84 (visit 3), 112 (visit 4) and 196 (visit 5).
Change in Transferrin
Following overnight fasting
Measured: Days 0 (visit 2), 84 (visit 3), 112 (visit 4) and 196 (visit 5).
Change in Retinol-binding protein
Following overnight fasting
Measured: Days 0 (visit 2), 84 (visit 3), 112 (visit 4) and 196 (visit 5).
Change in Glucose
Following overnight fasting
Measured: Days 0 (visit 2), 84 (visit 3), 112 (visit 4) and 196 (visit 5).
Change in Haemoglobin A1C
Following overnight fasting
Measured: Days 0 (visit 2), 84 (visit 3), 112 (visit 4) and 196 (visit 5).
Change in IGF-1
Following overnight fasting
Measured: Days 0 (visit 2), 84 (visit 3), 112 (visit 4) and 196 (visit 5).
Change in C-peptide
Following overnight fasting
Measured: Days 0 (visit 2), 84 (visit 3), 112 (visit 4) and 196 (visit 5).
Change in Short chain fatty acids
Following overnight fasting
Measured: Days 0 (visit 2), 84 (visit 3), 112 (visit 4) and 196 (visit 5).
Change insulin production
Following overnight fasting
Measured: Days 0 (visit 2), 84 (visit 3), 112 (visit 4) and 196 (visit 5).
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).
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).
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).
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).
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).
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).
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).
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).
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).
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).
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).
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).
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).
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).
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).
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).
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).
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).
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).
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).
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).
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).
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).
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).
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).
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).
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).
Change in Serum myeloid-related protein
Following overnight fasting
Measured: Days 0 (visit 2), 84 (visit 3), 112 (visit 4) and 196 (visit 5).
Change in Soluble Interleukin 2 Receptor
Following overnight fasting
Measured: Days 0 (visit 2), 84 (visit 3), 112 (visit 4) and 196 (visit 5).
Change in Inflammatory cytokine panel
Following overnight fasting
Measured: Days 0 (visit 2), 84 (visit 3), 112 (visit 4) and 196 (visit 5).
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).
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).
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).
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)
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.
- First posted3 Sep 2019
- Study start26 Apr 2019
- Primary completion31 Jan 2023
- Study completion31 Jan 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for PhenylketonuriasStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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)
Sponsor and investigators
- Lead sponsor
- Vitaflo International, Ltd
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Arla Foods
- Responsible party
- Sponsor
- Investigators
- Anita MacDonald, Principal investigator, Birmingham Women's and Children's NHS Foundation Trust
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
Study at a glance
From the registry record, last updated by the sponsor on 20 Aug 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effects Of Casein Glycomacropeptide On Metabolic Control And General Health Status In Children And Adults With PKU: A Randomised Crossover Trial
- ClinicalTrials.gov ID
- NCT04076176
- Acronym / sponsor ID
- ELEMENT / MCT-CGMP-2017-05-23
- Conditions
- Phenylketonurias
- Keywords
- Phenylketonuria, PKU, Child, Adult, GMP, Glycomacropeptide
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 12 participants (actual)
- Lead sponsor
- Vitaflo International, LtdIndustry (pharma, biotech, devices)
- Collaborators
- Arla Foods
- Study start
- 26 Apr 2019 (actual)
- Primary completion
- 31 Jan 2023 (actual)
- Study completion
- 31 Jan 2023 (actual)
- First posted
- 3 Sep 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| L-amino Acids | Active comparator | Dietary Supplement: L-amino acid protein substituteThe 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. |
| PKU Sphere | Experimental | Dietary Supplement: CGMP protein substituteThe 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. |
Who may qualify
- Ages
- 4 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (15 listed)
- 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).
Key exclusion criteria (7 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CGMP protein substituteAlso: PKU SpherePKU 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. | Dietary supplement | PKU Sphere |
| L-amino acid protein substitutePatient may choose from a list of products, specified in the protocol, that are nutritionally comparable to PKU Sphere. | Dietary supplement | L-amino Acids |
Primary outcome
Change in overnight fasting plasma Phe
Time frame: Measured at days 0 (visit 2), 84 (visit 3), 112 (visit 4) and 196 (visit 5)
Overnight fasting plasma phenylalanine level (μmol/l)
Change in overnight fasting plasma Tyr
Time frame: Measured at days 0 (visit 2), 84 (visit 3), 112 (visit 4) and 196 (visit 5)
Overnight fasting plasma tyrosine level (μmol/l)
Change in overnight fasting blood Phe
Time frame: Measured twice per week up to 32 weeks
Overnight fasting blood phenylalanine level (μmol/l) using blood spots
Change in overnight fasting blood Tyr
Time frame: Measured twice per week up to 32 weeks
Overnight fasting blood tyrosine level (μmol/l) using blood spots
54 secondary outcomes
Change in gut health: PedsQL Gastrointestinal Symptoms Scales, Version 3.0
Time frame: Days 0 (visit 2), 84 (visit 3), 112 (visit 4) and 196 (visit 5).
Change in gut health: Stool pH for reducing sugars
Time frame: Days 0 (visit 2), 84 (visit 3), 112 (visit 4) and 196 (visit 5).
Change in gut health: Stool calprotectin
Time frame: Days 0 (visit 2), 84 (visit 3), 112 (visit 4) and 196 (visit 5).
Change in gut health: Short chain fatty acids
Time frame: Days 0 (visit 2), 84 (visit 3), 112 (visit 4) and 196 (visit 5).
Change in gut health: Immunoglobulin A
Time frame: Days 0 (visit 2), 84 (visit 3), 112 (visit 4) and 196 (visit 5).
Change in gut health: Bristol stool form scale
Time frame: Completed for 7 days prior to days 0 (visit 2), 84 (visit 3), 112 (visit 4) and 196 (visit 5).
Change in gut health: 3 day weighed diet diary
Time frame: Completed for 3 days prior to days 0 (visit 2), 84 (visit 3), 112 (visit 4) and 196 (visit 5).
Change in anthropometric measurements: weight
Time frame: Days -31 (visit 1), 0 (visit 2), 84 (visit 3), 112 (visit 4) and 196 (visit 5).
Change in anthropometric measurements: height
Time frame: Days -31 (visit 1), 0 (visit 2), 84 (visit 3), 112 (visit 4) and 196 (visit 5).
Change in Albumin
Time frame: Days 0 (visit 2), 84 (visit 3), 112 (visit 4) and 196 (visit 5).
Change in Pre-albumin
Time frame: Days 0 (visit 2), 84 (visit 3), 112 (visit 4) and 196 (visit 5).
Change in Transferrin
Time frame: Days 0 (visit 2), 84 (visit 3), 112 (visit 4) and 196 (visit 5).
Change in Retinol-binding protein
Time frame: Days 0 (visit 2), 84 (visit 3), 112 (visit 4) and 196 (visit 5).
Change in Glucose
Time frame: Days 0 (visit 2), 84 (visit 3), 112 (visit 4) and 196 (visit 5).
Change in Haemoglobin A1C
Time frame: Days 0 (visit 2), 84 (visit 3), 112 (visit 4) and 196 (visit 5).
Change in IGF-1
Time frame: Days 0 (visit 2), 84 (visit 3), 112 (visit 4) and 196 (visit 5).
Change in C-peptide
Time frame: Days 0 (visit 2), 84 (visit 3), 112 (visit 4) and 196 (visit 5).
Change in Short chain fatty acids
Time frame: Days 0 (visit 2), 84 (visit 3), 112 (visit 4) and 196 (visit 5).
Change insulin production
Time frame: Days 0 (visit 2), 84 (visit 3), 112 (visit 4) and 196 (visit 5).
Change in alanine
Time frame: Days 0 (visit 2), 84 (visit 3), 112 (visit 4) and 196 (visit 5).
Change in arginine
Time frame: Days 0 (visit 2), 84 (visit 3), 112 (visit 4) and 196 (visit 5).
Change in asparagine
Time frame: Days 0 (visit 2), 84 (visit 3), 112 (visit 4) and 196 (visit 5).
Change in citrulline
Time frame: Days 0 (visit 2), 84 (visit 3), 112 (visit 4) and 196 (visit 5).
Change in cystine
Time frame: Days 0 (visit 2), 84 (visit 3), 112 (visit 4) and 196 (visit 5).
Change in glutamate
Time frame: Days 0 (visit 2), 84 (visit 3), 112 (visit 4) and 196 (visit 5).
Change in glutamine
Time frame: Days 0 (visit 2), 84 (visit 3), 112 (visit 4) and 196 (visit 5).
Change in glycine
Time frame: Days 0 (visit 2), 84 (visit 3), 112 (visit 4) and 196 (visit 5).
Change in histidine
Time frame: Days 0 (visit 2), 84 (visit 3), 112 (visit 4) and 196 (visit 5).
Change in isoleucine
Time frame: Days 0 (visit 2), 84 (visit 3), 112 (visit 4) and 196 (visit 5).
Change in leucine
Time frame: Days 0 (visit 2), 84 (visit 3), 112 (visit 4) and 196 (visit 5).
Change in lysine
Time frame: Days 0 (visit 2), 84 (visit 3), 112 (visit 4) and 196 (visit 5).
Change in methionine
Time frame: Days 0 (visit 2), 84 (visit 3), 112 (visit 4) and 196 (visit 5).
Change in proline
Time frame: Days 0 (visit 2), 84 (visit 3), 112 (visit 4) and 196 (visit 5).
Change in ornithine
Time frame: Days 0 (visit 2), 84 (visit 3), 112 (visit 4) and 196 (visit 5).
Change in phenylalanine
Time frame: Days 0 (visit 2), 84 (visit 3), 112 (visit 4) and 196 (visit 5).
Change in serine
Time frame: Days 0 (visit 2), 84 (visit 3), 112 (visit 4) and 196 (visit 5).
Change in taurine
Time frame: Days 0 (visit 2), 84 (visit 3), 112 (visit 4) and 196 (visit 5).
Change in threonine
Time frame: Days 0 (visit 2), 84 (visit 3), 112 (visit 4) and 196 (visit 5).
Change in tryptophan
Time frame: Days 0 (visit 2), 84 (visit 3), 112 (visit 4) and 196 (visit 5).
Change in tyrosine
Time frame: Days 0 (visit 2), 84 (visit 3), 112 (visit 4) and 196 (visit 5).
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Aug 2025.
- Results publication: PubMed 39579672Pinto 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Anita MacDonald principal investigator
Birmingham Women's and Children's NHS Foundation Trust
3 sites in 2 countries: see every site and its status.
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.