Phenylketonurias
Conditions
Brief summary
This is a 2 arm, randomised, controlled, cross-over study in 16 children with PKU. Subjects who are currently taking a Phe free/low Phe protein substitute will be recruited for a 31-day trial. Patients will be randomised to receive: 1. The study product for 7 days as their last dose of protein substitute for the day (at least one sachet with 15g PE) in an amount equivalent to their usual protein substitute PE; or 2. An amino acid protein substitute for all daily doses for 7 days; followed by a 2-week washout period on their usual protein substitute, and then 7 days of the other study arm. During this time, patients/caregivers will be asked to: * Collect 3 finger prick blood spots on days -1, 0, 6, 7, 20, 21, 27 and 28. * Collect urine sample, second void of the day on days 0, 7, 21 and 28. * Complete a questionnaire on sleep quality on day 0, 7, 21 and 28. * Complete a 24 hour food diary on days -1, 0, 6, 7, 20, 21, 27 and 28. APR will supply the study product for participants free of charge.
Detailed description
16 children with PKU who currently take a Phe-free/low Phe protein substitute (3 or 4 doses/day) will be recruited. Subjects will replace the last daily dose of their usual protein substitute with the study product for 7 days of the 28 day trial (either days 1-7 or days 22-28 based on random allocation). On the remaining study days, subjects will take an amino acid based protein substitute for all daily doses. There will be a 2 week washout period between study arms where subjects will take their usual protein substitute. The amount of study product prescribed will be calculated to provide the same amount of protein as their usual protein substitute. The last protein substitute (PS) dose of the day (amino acids or study product) will need to be taken between 7-9pm to allow an 8-10 hour fasting period overnight. Three finger prick blood spots will be collected and analysed for phenylalanine, tyrosine and BCAA at 5am, 6am and 7am on days -1, 0, 6, 7, 20, 21, 27 and 28. For all subjects, a second void urine sample will be collected on days 0, 7, 21 and 28 for analysis of urea and creatinine. A quality of sleep questionnaire will be completed by subjects or their carers on days 0, 7, 21 and 28 and a 24 hour food diary on days -1, 0, 6, 7, 20, 21, 27 and 28. A palatability questionnaire will be completed by subjects or their carers on days 7 or 28 (at the end of the period with PKU GOLIKE, if Bars or Krunches are used). Subject visits will be on days -2 (enrolment), 0, 7, 21 and 28 where the research dietitian will collect urine samples, blood spots, questionnaires and diaries.
Interventions
DIETARY_SUPPLEMENTPKU GOLIKE
AA protein Substitute for the dietary management of PKU, PKU GOLIKE is a food for special medicinal purposes (FSMP) for the dietary management of PKU.
Sponsors
APR Applied Pharma Research s.a.
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
5 Years to 16 Years
Healthy volunteers
No
Inclusion criteria
1. Male and female PKU patients ≥5 years and ≤16 years of age. 2. Patients diagnosed with PKU via new born screening. 3. Taking a Phe free/low Phe protein substitute 4. On a low phenylalanine diet . 5. Absence of neurological deficiencies. 6. Adherence with dietary management and protein substitute. 7. Able to understand and comply with the requirements of the investigation and sign the Informed Consent Form/Assent form.
Exclusion criteria
1. Age \<5 years old and \>16 years old. 2. Patients with mild PKU or HPA. 3. On sapropterin therapy. 4. Patients with late diagnosis of PKU and neurological problems. 5. History of hypersensitivity to any excipients/components of the investigational product. 6. Pregnancy or breastfeeding during the study. 7. Any moderate to severe acute illness which in the opinion of the Investigator would interfere with the study procedures or study outcome. 8. History of poor co-operation, non-adherence with dietary management, or poor adherence to investigation procedures. 9. Participation in any other studies involving investigational or marketed products concomitantly or within two weeks prior to entry into the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Blood Phe After 7 Days of Each Treatment | Mean value of Blood Sample after 7 treatment days (days 7 and 28 together depending on the period) | Measurement of blood phenylalanine (Phe) levels |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Dosage of Tyr in Blood (Umol/L) With Dried Blood Spots Before Breakfast | Mean value of Blood Sample after 7 treatment days (days 7 and 28 together depending on the period) | Measurement of blood tyrosine (Tyr) levels |
Countries
United Kingdom
Contacts
PRINCIPAL_INVESTIGATORAnita MacDonald, Pr.
Birmingham Children's Hospital, Steelhouse Lane, Birmingham B4 6NH
Participant flow
Recruitment details
Participants were recruited at Birmingham Hospital from June 2023 to February 2024. The first participant was enrolled on 30 June 2023 (date of informed consent signature), and the last participant was enrolled in February 2024.
Pre-assignment details
16 patients are recruited in the study and treated according to the study design: randomised two-periods crossover. 3 patients are excluded from analyses due to protocol deviations. So 16 patients are included in the ITT analysis and only 13 in the PP analysis.
Participants by arm
| Arm | Count |
|---|---|
| All Study Participants (ITT) For the study All Patients are randomised to receive:
* The PKU GOLIKE treatment for 7 days as their last dose of protein substitute for the day in an amount equivalent to their usual protein substitute Proteine Equivalent; or
* An amino acid protein substitute (AA treatment) for all daily doses for 7 days.
Each the above mentioned treatments were followed by a 2-week washout period on their usual protein substitute, and then 7 days of the other study arm.
All participants were randomized to receive both Golike and AA treatments | 16 |
| Total | 16 |
Baseline characteristics
| Characteristic | All Study Participants (ITT) |
|---|---|
| Age, Continuous | 11.19 years STANDARD_DEVIATION 3.29 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 2 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 14 Participants |
| Region of Enrollment United Kingdom | 16 participants |
| Sex: Female, Male Female | 8 Participants |
| Sex: Female, Male Male | 8 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 16 | 0 / 16 |
| other Total, other adverse events | 4 / 16 | 1 / 16 |
| serious Total, serious adverse events | 0 / 16 | 0 / 16 |
Outcome results
Primary
Blood Phe After 7 Days of Each Treatment
Measurement of blood phenylalanine (Phe) levels
Time frame: Mean value of Blood Sample after 7 treatment days (days 7 and 28 together depending on the period)
Population: In this cross-over study, the analysis was conducted by grouping patients data from both arms based on the type of treatment (Golike or AA) used for 7 days.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| All Study Participants | Blood Phe After 7 Days of Each Treatment | Phe level Before All study partecipants from both arms start GolikeTreatment | 357.5 µmol/L | Standard Deviation 155.58 |
| All Study Participants | Blood Phe After 7 Days of Each Treatment | Phe level After All study Partcipants from both arms are 7 days treated with Golike Treatment | 294.0 µmol/L | Standard Deviation 149.93 |
| All Study Participants | Blood Phe After 7 Days of Each Treatment | Phe level Before All study partecipants from both arms start AA Treatment | 346.8 µmol/L | Standard Deviation 143.72 |
| All Study Participants | Blood Phe After 7 Days of Each Treatment | Phe level After All study Partcipants from both arms are 7 days treated with AA Treatment | 442.4 µmol/L | Standard Deviation 177.58 |
Secondary
Dosage of Tyr in Blood (Umol/L) With Dried Blood Spots Before Breakfast
Measurement of blood tyrosine (Tyr) levels
Time frame: Mean value of Blood Sample after 7 treatment days (days 7 and 28 together depending on the period)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| All Study Participants | Dosage of Tyr in Blood (Umol/L) With Dried Blood Spots Before Breakfast | Tyr level Before All study partecipants from both arms start GolikeTreatment | 46.4 µmol/L | Standard Deviation 15.76 |
| All Study Participants | Dosage of Tyr in Blood (Umol/L) With Dried Blood Spots Before Breakfast | Tyr level after All study partecipants from both arms are 7 days treated with GolikeTreatment | 62.1 µmol/L | Standard Deviation 23.43 |
| All Study Participants | Dosage of Tyr in Blood (Umol/L) With Dried Blood Spots Before Breakfast | Tyr level Before All study partecipants from both arms start AA Treatment | 49.5 µmol/L | Standard Deviation 11.93 |
| All Study Participants | Dosage of Tyr in Blood (Umol/L) With Dried Blood Spots Before Breakfast | Tyr level after All study partecipants from both arms are 7 days treated with AA Treatment | 51.6 µmol/L | Standard Deviation 22.02 |