PhenylketonuriasNCT04679467
Evaluation of PKU Sphere in Italy
A study testing PKU sphere in people with Phenylketonurias and PKU, run by Vitaflo International, Ltd at 4 sites in Italy.
Trial summary
20 participants with PKU will build-up their dietary intake of PKU sphere over 2-16 weeks, depending on their level of metabolic control whilst doing so. Participants will complete a gastrointestinal specific and PKU specific questionnaire at the Baseline clinic visit and record the amount of PKU sphere taken each… Read more about this study
- Who is it for?
- Ages 3 years and older
- Conditions the study is for
- Phenylketonurias, PKU
- What is being tested?
- PKU sphere
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 13 participants
- Where
- 4 sitesItaly
- Study dates
- 10 Aug 2020to 31 Jul 2022
- 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 3 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Patients diagnosed with PKU or hyperphenylalaninemia via new born screening and early treated, requiring >50% of protein intake from protein substitute.
- Aged 3 years and above.
- Female patients of childbearing potential must have a negative urine pregnancy test prior to completing the screening procedures.
- Willingly given, written, informed consent from the participant, 18 or more years, or from the parent/guardian for participants < 18 years.
- Willingly given, written assent (if appropriate) for those < 18 years.
Who cannot join
- Pregnant, planning pregnancy or breastfeeding.
- Intake of sapropterin dihydrochloride (Kuvan), PEG PAL or large neutral amino acids within 30 days prior to screening visit.
- Patients currently taking their maximum recommended amount of protein substitute from a GMP based protein substitute.
- Patients who are unable/unwilling to replace their current GMP protein substitute (if any) with PKU sphere.
- Patients with known soya, milk or fish allergies / intolerance.
- Individuals, who in the opinion of the investigator, are unable to comply with the requirements of the protocol.
- Any co-morbidity, which in the opinion of the Investigator, would preclude participation in the study.
- 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.
Trial locations and contacts
4 sites in 1 country.
Italy4 sites
Sant'Orsola-Malpighi Polyclinic (adults)
Bologna
Sant'Orsola-Malpighi Polyclinic (paediatrics)
Bologna
Ospedale San Paolo
Milan
A.O.R.N. Santobono-Pausilipon - Ospedale Santobono
Naples
About this study
Official title: An Acceptability Study to Evaluate the Tolerance, Adherence and Metabolic Control of Patients With Phenylketonuria (PKU) Consuming PKU Sphere™, a Glycomacropeptide (GMP) Based Protein Substitute, When Introduced According to a Practical Guide to PKU Sphere.
20 participants with PKU will build-up their dietary intake of PKU sphere over 2-16 weeks, depending on their level of metabolic control whilst doing so. Participants will complete a gastrointestinal specific and PKU specific questionnaire at the Baseline clinic visit and record the amount of PKU sphere taken each day. Dried blood spots are taken twice per week.
Once built up to a clinically appropriate intake of PKU sphere, or after 16 weeks, participants enter a 4-week Evaluation Period. The amount of PKU sphere taken per day continues to be recorded by participants. Gastrointestinal tolerance over the preceding seven days is recorded at the end of each week. Evaluations of PKU sphere's palatability are made at the end of weeks two and four of the Evaluation Period. Dried blood spots are taken once per week.
The participant attends an End of Study Visit at the clinic and the investigator decides whether they should continue taking PKU sphere.
Read the detailed description
20 participants with phenylketonuria (PKU) will introduce PKU sphere into their diet. PKU sphere is a food for special medical purposes (as defined by Regulation (EU) No 609/2013 on food for specific groups), used for the dietary management of phenylketonuria from 3 years of age.
The study begins with a Baseline clinic visit. Informed consent is taken by the investigator before the participant completes a PKU specific quality of life questionnaire, and a GI specific questionnaire. The participant takes a dried blood spot in order for the investigator to check their technique is correct.
Build-up and Stabilisation Period. This will last between 2 and 16 weeks, depending on how long the participant takes to reach their maximum recommended intake of PKU sphere. Participants will take a dried blood spot twice per week in order for their health care professional to monitor their phenylalanine and tyrosine levels. After three consecutive dried blood spot results within the target range, the participant's HCP can advise to swap one portion of amino acid-based protein substitute for PKU sphere. This method of building up the amount of PKU sphere to be taken is informed directly by Vitaflo's 'Practical Guide to PKU sphere'. The amount of PKU sphere taken each day is recorded by the participant in their study diary.
Once the maximum recommended amount of PKU sphere is being taken by the participant, or after 16 weeks, the participant moves into the four-week Evaluation Period. Participants then take a dried blood spot once per week, but continue to record their intake of PKU sphere each day. At the end of each Evaluation Period week, participants record any gastrointestinal symptoms experienced over the preceding seven days. At the end of Evaluation Period weeks two and four, participants will also record their thoughts on PKU sphere's palatability. This includes a Likert scale rating of the product's appearance, taste, aftertaste, smell, texture, packaging and ease of use.
At the end of the Evaluation Period, participants return to the clinic for the End of Study visit. The PKU and GI specific questionnaires completed at Baseline are repeated and the Investigator discusses the suitability of the participant to continue to take PKU sphere as part of their regular therapeutic diet. Following the visit, the Investigator rates the utility of the Practical Guide to PKU sphere. A Follow-up Phone Call will relay the results of any outstanding dried blood spot results to participants following their End of Study Visit.
- Conditions
- Phenylketonurias, PKU
- Being tested
- PKU sphere
- Keywords
- Phenylketonuria, PKU, Glycomacropeptide, Food for Special Medical Purposes
- Medical subject headings
- Phenylketonurias
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PKU sphereDietary supplement
TYR sphere is a powdered, low phenylalanine and tyrosine protein substitute, containing a balanced mix of casein glycomacropeptide (cGMP) isolate, essential and non-essential amino acids, carbohydrate, fat, vitamins, minerals and the long chain polyunsaturated fatty acid (LCP); Docosahexaenoic acid (DHA). It contains sugars and sweetener.
The product is designed to be prescribed based on its protein content, not its energy content.
| Study group | Role | What they receive |
|---|---|---|
| Experimental - single arm | Experimental | All patients to recieve PKU sphere as part of their dietary management for phenylketonuria (PKU) Receives: Dietary Supplement: PKU sphere |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in adherence to recomended amounts of PKU sphere
Patient reported data on actual compared to prescribed intakes of PKU sphere
Measured: Recorded daily from start of 2-16 week Build-up and Stabilisation Period to end of 4 week Evaluation Period, assessed by HCPs periodically as per routine practice.
Change in gastrointestinal tolerance
Patient reported data on any gastrointestinal symptoms experienced
Measured: Data on previous 7 days collected by patients at the end of each Evaluation Period week. This data will be assessed by HCPs periodically as per routine practice.
Patient evaluation of PKU sphere's palatability, Evaluation Period week 2
Patient reported Likert-scale evaluation of PKU sphere's appearance, smell, taste, aftertaste, texture, packaging/presentation and ease of use. A higher score denotes a more positive response.
Measured: End of Evaluation Period week 2.
Patient evaluation of PKU sphere's palatability, Evaluation Period week 4
Patient reported Likert-scale evaluation of PKU sphere's appearance, smell, taste, aftertaste, texture, packaging/presentation and ease of use. A higher score denotes a more positive response.
Measured: End of Evaluation Period week 4.
Change in metabolic control (phenylalanine) over Build-up and Stabilisation Period.
Phenylalanine levels obtained from dried blood spots
Measured: Dried blood spots taken twice weekly during 2-16 week Build-up and Stabilisation Period.
Change in metabolic control (phenylalanine) over Evaluation Period.
Phenylalanine levels obtained from dried blood spots
Measured: Dried blood spots taken once weekly during 4-week Evaluation Period.
Change in metabolic control (tyrosine) over Build-up and Stabilisation Period.
Tyrosine levels obtained from dried blood spots
Measured: Dried blood spots taken twice weekly during 2-16 week Build-up and Stabilisation Period.
Change in metabolic control (tyrosine) over Evalaution Period.
Tyrosine levels obtained from dried blood spots
Measured: Dried blood spots taken once weekly during 4-week Evalaution Period.
Change in gatrointestinal quality of life
Age-specific, GI related quality of life questionnaire completed by participants. The specific version of the questionnaire to be used by each age group is listed below:
Age 2-4 years (Parental completion) = MAPI PedsQL Gastrointestinal Symptoms Scales, Toddlers (2-4) Age 5-7 years (Parental completion) = MAPI PedsQL Gastrointestinal Symptoms Scales, Young Children (5-7) Age 8-12 years (Parental completion) = MAPI PedsQL Gastrointestinal Symptoms Scales, Children (8-12) Age 13-18 years = MAPI PedsQL Gastrointestinal Symptoms Scales, Teens (13-18) Age 18 years and upwards = Birmingham IBS Symptom Questionnaire
The MAPI PedsQL Gastrointestinal Symptoms Scale questionnaires and the Birmingham IBS symptom Questionnaire indicate fewer problems with higher calculated scores.
Measured: Baseline visit (day one) and End of Study visit (post day-28 of Evaluation Period)
Change in PKU specific quality of life
Age-specific, PKU related quality of life questionnaire completed by participants. The specific version of the questionnaire to be used by each age group is listed below:
Age >9 years = MAPI phenylketonuria impact and treatment Quality Of Life Questionnaire (PKU-QOL), Parents Age 9-11 years = MAPI phenylketonuria impact and treatment Quality Of Life Questionnaire (PKU-QOL), Children Age 12-17 years = MAPI phenylketonuria impact and treatment Quality Of Life Questionnaire (PKU-QOL), Adolescent Age 18+ years = MAPI phenylketonuria impact and treatment Quality Of Life Questionnaire (PKU-QOL), Adult
With all versions of the PKU-QOL, a higher calculated score denotes higher quality of life.
Measured: Baseline visit (day one) and End of Study visit (post day-28 of Evaluation Period)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Dec 2020
- Study start10 Aug 2020
- Primary completion31 Jul 2022
- Study completion31 Jul 2022
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
- Supportive care
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Open-label, single group interventional study.
- Masking
- None (open label)
- Enrolment
- 13 participants (actual)
Sponsor and investigators
- Lead sponsor
- Vitaflo International, Ltd
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Giulio Marchesini Reggiani, Principal investigator, Universita di Bologna
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04679467
- Sponsor's protocol ID
- MCT-W-GMPIT-2019-03-08
- Status last verified
- May 2026
- First submitted
- 26 Nov 2020
- Last updated
- 14 May 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 14 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Acceptability Study to Evaluate the Tolerance, Adherence and Metabolic Control of Patients With Phenylketonuria (PKU) Consuming PKU Sphere™, a Glycomacropeptide (GMP) Based Protein Substitute, When Introduced According to a Practical Guide to PKU Sphere.
- ClinicalTrials.gov ID
- NCT04679467
- Acronym / sponsor ID
- MCT-W-GMPIT-2019-03-08
- Conditions
- Phenylketonurias, PKU
- Keywords
- Phenylketonuria, PKU, Glycomacropeptide, Food for Special Medical Purposes
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 13 participants (actual)
- Lead sponsor
- Vitaflo International, LtdIndustry (pharma, biotech, devices)
- Study start
- 10 Aug 2020 (actual)
- Primary completion
- 31 Jul 2022 (actual)
- Study completion
- 31 Jul 2022 (actual)
- First posted
- 22 Dec 2020 (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.
20 participants with PKU will build-up their dietary intake of PKU sphere over 2-16 weeks, depending on their level of metabolic control whilst doing so. Participants will complete a gastrointestinal specific and PKU specific questionnaire at the Baseline clinic visit and record the amount of PKU sphere taken each day. Dried blood spots are taken twice per week.
Once built up to a clinically appropriate intake of PKU sphere, or after 16 weeks, participants enter a 4-week Evaluation Period. The amount of PKU sphere taken per day continues to be recorded by participants. Gastrointestinal tolerance over the preceding seven days is recorded at the end of each week. Evaluations of PKU sphere's palatability are made at the end of weeks two and four of the Evaluation Period. Dried blood spots are taken once per week.
The participant attends an End of Study Visit at the clinic and the investigator decides whether they should continue taking PKU sphere.
Detailed description
20 participants with phenylketonuria (PKU) will introduce PKU sphere into their diet. PKU sphere is a food for special medical purposes (as defined by Regulation (EU) No 609/2013 on food for specific groups), used for the dietary management of phenylketonuria from 3 years of age.
The study begins with a Baseline clinic visit. Informed consent is taken by the investigator before the participant completes a PKU specific quality of life questionnaire, and a GI specific questionnaire. The participant takes a dried blood spot in order for the investigator to check their technique is correct.
Build-up and Stabilisation Period. This will last between 2 and 16 weeks, depending on how long the participant takes to reach their maximum recommended intake of PKU sphere. Participants will take a dried blood spot twice per week in order for their health care professional to monitor their phenylalanine and tyrosine levels. After three consecutive dried blood spot results within the target range, the participant's HCP can advise to swap one portion of amino acid-based protein substitute for PKU sphere. This method of building up the amount of PKU sphere to be taken is informed directly by Vitaflo's 'Practical Guide to PKU sphere'. The amount of PKU sphere taken each day is recorded by the participant in their study diary.
Once the maximum recommended amount of PKU sphere is being taken by the participant, or after 16 weeks, the participant moves into the four-week Evaluation Period. Participants then take a dried blood spot once per week, but continue to record their intake of PKU sphere each day. At the end of each Evaluation Period week, participants record any gastrointestinal symptoms experienced over the preceding seven days. At the end of Evaluation Period weeks two and four, participants will also record their thoughts on PKU sphere's palatability. This includes a Likert scale rating of the product's appearance, taste, aftertaste, smell, texture, packaging and ease of use.
At the end of the Evaluation Period, participants return to the clinic for the End of Study visit. The PKU and GI specific questionnaires completed at Baseline are repeated and the Investigator discusses the suitability of the participant to continue to take PKU sphere as part of their regular therapeutic diet. Following the visit, the Investigator rates the utility of the Practical Guide to PKU sphere. A Follow-up Phone Call will relay the results of any outstanding dried blood spot results to participants following their End of Study Visit.
Study design
- Primary purpose
- Supportive care
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Open-label, single group interventional study.
| Arm | Type | Receives |
|---|---|---|
| Experimental - single arm | Experimental | Dietary Supplement: PKU sphereAll patients to recieve PKU sphere as part of their dietary management for phenylketonuria (PKU) |
Who may qualify
- Ages
- 3 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (5 listed)
- Patients diagnosed with PKU or hyperphenylalaninemia via new born screening and early treated, requiring >50% of protein intake from protein substitute.
- Aged 3 years and above.
- Female patients of childbearing potential must have a negative urine pregnancy test prior to completing the screening procedures.
- Willingly given, written, informed consent from the participant, 18 or more years, or from the parent/guardian for participants < 18 years.
- Willingly given, written assent (if appropriate) for those < 18 years.
Key exclusion criteria (8 listed)
- Pregnant, planning pregnancy or breastfeeding.
- Intake of sapropterin dihydrochloride (Kuvan), PEG PAL or large neutral amino acids within 30 days prior to screening visit.
- Patients currently taking their maximum recommended amount of protein substitute from a GMP based protein substitute.
- Patients who are unable/unwilling to replace their current GMP protein substitute (if any) with PKU sphere.
- Patients with 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 |
|---|---|---|
| PKU sphereTYR sphere is a powdered, low phenylalanine and tyrosine protein substitute, containing a balanced mix of casein glycomacropeptide (cGMP) isolate, essential and non-essential amino acids, carbohydrate, fat, vitamins, minerals and the long chain polyunsaturated fatty acid (LCP); Docosahexaenoic acid (DHA). It contains sugars and sweetener. The product is designed to be prescribed based on its protein content, not its energy content. | Dietary supplement | Experimental - single arm |
Primary outcome
Change in adherence to recomended amounts of PKU sphere
Time frame: Recorded daily from start of 2-16 week Build-up and Stabilisation Period to end of 4 week Evaluation Period, assessed by HCPs periodically as per routine practice.
Patient reported data on actual compared to prescribed intakes of PKU sphere
Change in gastrointestinal tolerance
Time frame: Data on previous 7 days collected by patients at the end of each Evaluation Period week. This data will be assessed by HCPs periodically as per routine practice.
Patient reported data on any gastrointestinal symptoms experienced
Patient evaluation of PKU sphere's palatability, Evaluation Period week 2
Time frame: End of Evaluation Period week 2.
Patient reported Likert-scale evaluation of PKU sphere's appearance, smell, taste, aftertaste, texture, packaging/presentation and ease of use. A higher score denotes a more positive response.
Patient evaluation of PKU sphere's palatability, Evaluation Period week 4
Time frame: End of Evaluation Period week 4.
Patient reported Likert-scale evaluation of PKU sphere's appearance, smell, taste, aftertaste, texture, packaging/presentation and ease of use. A higher score denotes a more positive response.
Change in metabolic control (phenylalanine) over Build-up and Stabilisation Period.
Time frame: Dried blood spots taken twice weekly during 2-16 week Build-up and Stabilisation Period.
Phenylalanine levels obtained from dried blood spots
Change in metabolic control (phenylalanine) over Evaluation Period.
Time frame: Dried blood spots taken once weekly during 4-week Evaluation Period.
Phenylalanine levels obtained from dried blood spots
Change in metabolic control (tyrosine) over Build-up and Stabilisation Period.
Time frame: Dried blood spots taken twice weekly during 2-16 week Build-up and Stabilisation Period.
Tyrosine levels obtained from dried blood spots
Change in metabolic control (tyrosine) over Evalaution Period.
Time frame: Dried blood spots taken once weekly during 4-week Evalaution Period.
Tyrosine levels obtained from dried blood spots
Change in gatrointestinal quality of life
Time frame: Baseline visit (day one) and End of Study visit (post day-28 of Evaluation Period)
Age-specific, GI related quality of life questionnaire completed by participants. The specific version of the questionnaire to be used by each age group is listed below: Age 2-4 years (Parental completion) = MAPI PedsQL Gastrointestinal Symptoms Scales, Toddlers (2-4) Age 5-7 years (Parental completion) = MAPI PedsQL Gastrointestinal Symptoms Scales, Young Children (5-7) Age 8-12 years (Parental completion) = MAPI PedsQL Gastrointestinal Symptoms Scales, Children (8-12) Age 13-18 years = MAPI PedsQL Gastrointestinal Symptoms Scales, Teens (13-18) Age 18 years and upwards = Birmingham IBS Symptom Questionnaire The MAPI PedsQL Gastrointestinal Symptoms Scale questionnaires and the Birmingham IBS symptom Questionnaire indicate fewer problems with higher calculated scores.
Change in PKU specific quality of life
Time frame: Baseline visit (day one) and End of Study visit (post day-28 of Evaluation Period)
Age-specific, PKU related quality of life questionnaire completed by participants. The specific version of the questionnaire to be used by each age group is listed below: Age >9 years = MAPI phenylketonuria impact and treatment Quality Of Life Questionnaire (PKU-QOL), Parents Age 9-11 years = MAPI phenylketonuria impact and treatment Quality Of Life Questionnaire (PKU-QOL), Children Age 12-17 years = MAPI phenylketonuria impact and treatment Quality Of Life Questionnaire (PKU-QOL), Adolescent Age 18+ years = MAPI phenylketonuria impact and treatment Quality Of Life Questionnaire (PKU-QOL), Adult With all versions of the PKU-QOL, a higher calculated score denotes higher quality of life.
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 14 May 2026.
- 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.
Giulio Marchesini Reggiani principal investigator
Universita di Bologna
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing PKU sphere in people with Phenylketonurias and PKU, run by Vitaflo International, Ltd at 4 sites in Italy.
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 5 inclusion and 8 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 14 May 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in Italy. 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 adherence to recomended amounts of PKU sphere (time frame: Recorded daily from start of 2-16 week Build-up and Stabilisation Period to end of 4 week Evaluation Period, assessed by HCPs periodically as per routine practice.). The study lists 10 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 14 May 2026; AzTrials last refreshed its copy on 6 Nov 2026.