PhenylketonuriasNCT05971563
Amino Acid Kinetics of GMP-AA in Healthy Human Volunteers
A study testing Casein, L-amino acids and CGMP-AA in people with Phenylketonurias, run by Birmingham Women's and Children's NHS Foundation Trust at 1 site in United Kingdom.
Trial summary
Children with phenylketonuria (PKU) are treated with a special diet supplemented with a synthetic protein based on amino acids. These have a poor taste and are inefficiently used by the body. A different type of synthetic protein, called glycomacropeptide is being tried in PKU. Read more about this study
- Who is it for?
- Ages 18 to 50 yearsHealthy volunteers can take part
- Conditions the study is for
- Phenylketonurias
- What is being tested?
- Casein, L-amino acids and CGMP-AA
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 18 Oct 2022to 31 Aug 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 18 to 50 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Male and female healthy subjects without PKU;
- 18 to 50 years of age;
- Female subjects with a negative urine pregnancy test prior to entry into the study and who are practicing an adequate method of birth control during the study;
- Good general health status proven by medical history and clinical laboratory values within normal limits or considered not clinically significant by the investigator;
- Non-smokers or not current smokers;
- Body mass index (BMI) between 18 and 30 kg/m2 and weight (kg)
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- No existence of disorders or any comorbidity.
- Willing to follow the study protocol and to take the study products;
- Able to understand study procedures and sign informed consent.
Who cannot join
- History of alcohol or drugs abuse;
- Smokers;
- Women who are pregnant, breast feeding, or planning to become pregnant during the course of the study;
- Received an investigational drug or device within 30 days (or 5 half-lives, whichever is longer) of dosing;
- Existence of any disorder, food allergy or comorbidity (clinically significant including gastrointestinal, renal, pulmonary, hepatic, cardiovascular and endocrine disorders) - to be decided by investigator from medical history;
- Current illness or infection that could interfere with the study;
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- Use of laxatives;
- Use of antibiotics in the last 3 months;
- Use of medication that could influence protein metabolism (like growth hormone, anabolic steroids, hormone replacement) - to be judged by the investigator;
- Participation in any clinical trial in the last 3 months;
- Blood donation within the past 3 months;
- On a medically prescribed diet;
- Unable to follow the study protocol or provide consent;
- Unable to take or tolerate one of the study products.
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
University Hospitals Birmingham NHS Foundation Trust
Birmingham, West Midlands, B15 2TT
About this study
Official title: Amino Acid Kinetics of GMP-AA Vs. Phenylalanine-free Amino Acids Compared with Natural Protein in Healthy Adults Volunteers
Children with phenylketonuria (PKU) are treated with a special diet supplemented with a synthetic protein based on amino acids. These have a poor taste and are inefficiently used by the body. A different type of synthetic protein, called glycomacropeptide is being tried in PKU. It tastes better than amino acids but it requires the addition of some extra amino acids which may worsen how well it is absorbed compared with traditional amino acid supplements. We will perform a 3-part trial in healthy adult volunteers to compare amino acids vs glycomacropeptide protein with a 'normal protein' (casein) to examine the absorption properties of these proteins. Volunteers will take one dose of each of the protein sources on 3 different days. Blood and urine samples will be collected examining the rate of absorption of amino acids over 5 hours on each study day.
Read the detailed description
In the USA, casein glycomacropeptide (CGMP), a low phenylalanine (Phe) 64-amino acid peptide derived from cheese whey, is widely promoted as a low Phe protein substitute in phenylketonuria (PKU). Protein substitute is composed of non-essential and essential amino acids which replace natural protein in the diet in order to enable normal growth and suppression of blood Phe levels.
It is suggested that CGMP has a slower absorption than usual protein substitute based on amino acids only (amino acids-AA). This compositional change may enhance protein utilization leading to improved blood Phe control. In PKU, any protein substitute that has its absorption closer to the normal 'physiological state' should be advantageous but pure CGMP is lacking in several essential and conditionally essential amino acids (e.g. tyrosine, leucine, tryptophan, histidine). To ensure that CGMP is safe for PKU, it is supplemented with deficient AA (CGMP-AA). Evidence from 'normal' nutritional research suggests that adding AA to natural protein (similar to CGMP-AA), worsens rather than improves efficiency of protein absorption. It is essential to ascertain if CGMP-AA enhances, worsens or has the same absorption when compared with traditional AA substitutes, particularly when prescribing CGMP-AA for children and maternal PKU. The investigators aim to perform a three-part, randomized, controlled, trial in healthy adult volunteers comparing absorption of CGMP-AA (study product 1) vs. AA (study product 2) vs. normal protein (casein) (study product 3). After overnight fasting, healthy volunteers will consume a standard dose of each of the study products. Over the course of 4 hours, plasma AA will be monitored 8 times and this will provide greater insight into the kinetic absorption of CGMP-AA in PKU. The investigators hope these results will add to existing safety and efficacy data about using CGMP-AA in PKU.
- Conditions
- Phenylketonurias
- Being tested
- Casein, L-amino acids, CGMP-AA
- Medical subject headings
- Phenylketonurias
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CaseinDietary supplement
Natural protein
L-amino acidsDietary supplement
Synthetic amino acids based protein substitute for Phenylketonuria
CGMP-AADietary supplement
Glycomacropeptide based protein substitute for Phenylketonuria
| Study group | Role | What they receive |
|---|---|---|
| Casein | Active comparator | Not described Receives: Dietary Supplement: Casein |
| Glycomacropeptide | Active comparator | Not described Receives: Dietary Supplement: CGMP-AA |
| L- amino acids | Active comparator | Not described Receives: Dietary Supplement: L-amino acids |
What is being measured
The primary outcome is the main question the study is designed to answer.
Total EAA concentrations
To compare the total EAA concentrations after oral ingestion of one dose of three different protein supplements: cGMP-AA vs. AA only vs. casein.
Measured: 240 minutes for each protein
Mean CMAX
Mean CMAX within 240 minutes of ingestion of each of the 3 proteins
Measured: 240 minutes for each protein
AUC of EAA's
AUC of EAA's within 240 minutes of ingestion of each of the 3 proteins
Measured: 240 minutes for each protein
Secondary outcomes (2)
Curve characteristics (Cmax)
Curve characteristics (Cmax) of the following quantities:
- LNAA;
- BCAA;
- Total AA;
- Tyrosine;
- Phenylalanine;
- Urea;
- Insulin.
Measured: 240 minutes for each protein
Curve characteristics (AUC)
Curve characteristics (AUC) of the following quantities:
- LNAA;
- BCAA;
- Total AA;
- Tyrosine;
- Phenylalanine;
- Urea;
- Insulin.
Measured: 240 minutes for each protein
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Aug 2023
- Study start18 Oct 2022
- Primary completion31 Aug 2023
- Study completion31 Aug 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- 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
- Other
- Allocation
- Randomised
- Intervention model
- Crossover
- Model description
- A three-way, randomized, controlled, open-label, crossover, single-dose clinical trial in healthy adult volunteers.
- Masking
- None (open label)
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- Birmingham Women's and Children's NHS Foundation Trust
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05971563
- Sponsor's protocol ID
- 281421
- Status last verified
- Jul 2023
- First submitted
- 13 Jul 2023
- Last updated
- 4 Mar 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: All materials, information (oral or written) and unpublished documentation provided to the Investigators (or any company/institution acting on their behalf), including this protocol and the patient Case Report Forms, are the exclusive property of the Research team and may not be given or disclosed, either in part or in whole, by any person to any third party without the prior express consent of the research team. Potential and recruited patients will be identified by a unique study number with only the local research staff having the corresponding list of full patient identifiers, which should be kept secure. CRFs will be labelled with patient initials and their unique study number. Laboratory results shall be labelled similarly having had patient-identifiable details removed. All unpublished information shall be kept confidential and shall not be published or disclosed to a third party without the prior written consent of the research team.
Study at a glance
From the registry record, last updated by the sponsor on 4 Mar 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Amino Acid Kinetics of GMP-AA Vs. Phenylalanine-free Amino Acids Compared with Natural Protein in Healthy Adults Volunteers
- ClinicalTrials.gov ID
- NCT05971563
- Acronym / sponsor ID
- 281421
- Conditions
- Phenylketonurias
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- Birmingham Women's and Children's NHS Foundation TrustUniversity, hospital or other
- Study start
- 18 Oct 2022 (actual)
- Primary completion
- 31 Aug 2023 (actual)
- Study completion
- 31 Aug 2023 (actual)
- First posted
- 2 Aug 2023 (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.
Children with phenylketonuria (PKU) are treated with a special diet supplemented with a synthetic protein based on amino acids. These have a poor taste and are inefficiently used by the body. A different type of synthetic protein, called glycomacropeptide is being tried in PKU. It tastes better than amino acids but it requires the addition of some extra amino acids which may worsen how well it is absorbed compared with traditional amino acid supplements. We will perform a 3-part trial in healthy adult volunteers to compare amino acids vs glycomacropeptide protein with a 'normal protein' (casein) to examine the absorption properties of these proteins. Volunteers will take one dose of each of the protein sources on 3 different days. Blood and urine samples will be collected examining the rate of absorption of amino acids over 5 hours on each study day.
Detailed description
In the USA, casein glycomacropeptide (CGMP), a low phenylalanine (Phe) 64-amino acid peptide derived from cheese whey, is widely promoted as a low Phe protein substitute in phenylketonuria (PKU). Protein substitute is composed of non-essential and essential amino acids which replace natural protein in the diet in order to enable normal growth and suppression of blood Phe levels.
It is suggested that CGMP has a slower absorption than usual protein substitute based on amino acids only (amino acids-AA). This compositional change may enhance protein utilization leading to improved blood Phe control. In PKU, any protein substitute that has its absorption closer to the normal 'physiological state' should be advantageous but pure CGMP is lacking in several essential and conditionally essential amino acids (e.g. tyrosine, leucine, tryptophan, histidine). To ensure that CGMP is safe for PKU, it is supplemented with deficient AA (CGMP-AA). Evidence from 'normal' nutritional research suggests that adding AA to natural protein (similar to CGMP-AA), worsens rather than improves efficiency of protein absorption. It is essential to ascertain if CGMP-AA enhances, worsens or has the same absorption when compared with traditional AA substitutes, particularly when prescribing CGMP-AA for children and maternal PKU. The investigators aim to perform a three-part, randomized, controlled, trial in healthy adult volunteers comparing absorption of CGMP-AA (study product 1) vs. AA (study product 2) vs. normal protein (casein) (study product 3). After overnight fasting, healthy volunteers will consume a standard dose of each of the study products. Over the course of 4 hours, plasma AA will be monitored 8 times and this will provide greater insight into the kinetic absorption of CGMP-AA in PKU. The investigators hope these results will add to existing safety and efficacy data about using CGMP-AA in PKU.
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 3
- Model description
- A three-way, randomized, controlled, open-label, crossover, single-dose clinical trial in healthy adult volunteers.
| Arm | Type | Receives |
|---|---|---|
| Casein | Active comparator | Dietary Supplement: Casein |
| Glycomacropeptide | Active comparator | Dietary Supplement: CGMP-AA |
| L- amino acids | Active comparator | Dietary Supplement: L-amino acids |
Who may qualify
- Ages
- 18 to 50 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (9 listed)
- Male and female healthy subjects without PKU;
- 18 to 50 years of age;
- Female subjects with a negative urine pregnancy test prior to entry into the study and who are practicing an adequate method of birth control during the study;
- Good general health status proven by medical history and clinical laboratory values within normal limits or considered not clinically significant by the investigator;
- Non-smokers or not current smokers;
Key exclusion criteria (14 listed)
- History of alcohol or drugs abuse;
- Smokers;
- Women who are pregnant, breast feeding, or planning to become pregnant during the course of the study;
- Received an investigational drug or device within 30 days (or 5 half-lives, whichever is longer) of dosing;
- Existence of any disorder, food allergy or comorbidity (clinically significant including gastrointestinal, renal, pulmonary, hepatic, cardiovascular and endocrine disorders) - to be decided by investigator from medical history;
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 |
|---|---|---|
| CaseinNatural protein | Dietary supplement | Casein |
| L-amino acidsSynthetic amino acids based protein substitute for Phenylketonuria | Dietary supplement | L- amino acids |
| CGMP-AAGlycomacropeptide based protein substitute for Phenylketonuria | Dietary supplement | Glycomacropeptide |
Primary outcome
Total EAA concentrations
Time frame: 240 minutes for each protein
To compare the total EAA concentrations after oral ingestion of one dose of three different protein supplements: cGMP-AA vs. AA only vs. casein.
Mean CMAX
Time frame: 240 minutes for each protein
Mean CMAX within 240 minutes of ingestion of each of the 3 proteins
AUC of EAA's
Time frame: 240 minutes for each protein
AUC of EAA's within 240 minutes of ingestion of each of the 3 proteins
2 secondary outcomes
Curve characteristics (Cmax)
Time frame: 240 minutes for each protein
Curve characteristics (AUC)
Time frame: 240 minutes for each protein
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 4 Mar 2025.
- Individual participant dataSharing planned: No. All materials, information (oral or written) and unpublished documentation provided to the Investigators (or any company/institution acting on their behalf), including this protocol and the patient Case Report Forms, are the exclusive property of the Research team and may not be given or disclosed, either in part or in whole, by any person to any third party without the prior express consent of the research team. Potential and recruited patients will be identified by a unique study number with only the local research staff having the corresponding list of full patient identifiers, which should be kept secure. CRFs will be labelled with patient initials and their unique study number. Laboratory results shall be labelled similarly having had patient-identifiable details removed. All unpublished information shall be kept confidential and shall not be published or disclosed to a third party without the prior written consent of the research team.
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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.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Casein, L-amino acids and CGMP-AA in people with Phenylketonurias, run by Birmingham Women's and Children's NHS Foundation Trust at 1 site in United Kingdom.
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 9 inclusion and 14 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 4 Mar 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. 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?
Total EAA concentrations (time frame: 240 minutes for each protein). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 4 Mar 2025.