Evaluation of Phe Fluctuation in PKU Pts Treated With PKU GOLIKE Versus Standard Amino Acid Protein Substitute.

Study Overview
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Brief Summary
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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: 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 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
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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.

Official Title
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Randomised Investigation to Evaluate Phe Fluctuation in PKU Patients Treated With PKU GOLIKE Versus Standard Amino Acid Protein Substitute.

Conditions
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Phenylketonurias

Intervention / Treatment
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* Dietary Supplement: PKU GOLIKE


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male and female PKU patients ≥5 years and ≤16 years of age. Patients diagnosed with PKU via new born screening. Taking a Phe free/low Phe protein substitute On a low phenylalanine diet . Absence of neurological deficiencies. Adherence with dietary management and protein substitute. Able to understand and comply with the requirements of the investigation and sign the Informed Consent Form/Assent form. Exclusion Criteria: Age <5 years old and >16 years old. Patients with mild PKU or HPA. On sapropterin therapy. Patients with late diagnosis of PKU and neurological problems. History of hypersensitivity to any excipients/components of the investigational product. Pregnancy or breastfeeding during the study. Any moderate to severe acute illness which in the opinion of the Investigator would interfere with the study procedures or study outcome. History of poor co-operation, non-adherence with dietary management, or poor adherence to investigation procedures. Participation in any other studies involving investigational or marketed products concomitantly or within two weeks prior to entry into the study.

Ages Eligible for Study
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Minimum Age: 5 Years
Maximum Age: 16 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: 1st PKU GOLIKE 2nd AA protein substitute<br>7 days with usual protein substitute and PKU GOLIKE as their last dose of protein substitute for the day (at least one sachet with15g PE) in an amount equivalent to their usual protein substitute PE followed by a 2-week washout period on their usual protein substitute, and then 7 days with AA protein substitute for all daily doses. | Dietary Supplement: PKU GOLIKE<br>* 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.<br>* Other names: PKU GOLIKE is a food for special medicinal purposes (FSMP) for the dietary management of PKU.;|
| Other: 1st AA protein substitute 2nd PKU GOLIKE<br>7 days with AA protein substitute for all daily doses followed by a 2-week washout period on their usual protein substitute, and then 7 days with usual protein substitute and PKU GOLIKE as their last dose of protein substitute for the day (at least one sachet with15g PE) in an amount equivalent to their usual protein substitute PE | Dietary Supplement: PKU GOLIKE<br>* 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.<br>* Other names: PKU GOLIKE is a food for special medicinal purposes (FSMP) for the dietary management of PKU.;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Blood Phe after administration of PKU GOLIKE and after amino acid protein substitute collected before breakfast |  | At 5:00 am on day 6 | 
| Blood Phe after administration of PKU GOLIKE and after amino acid protein substitute collected before breakfast |  | At 5:00 am on day 7 | 
| Blood Phe after administration of PKU GOLIKE and after amino acid protein substitute collected before breakfast |  | At 5:00 am on day 27 | 
| Blood Phe after administration of PKU GOLIKE and after amino acid protein substitute collected before breakfast |  | At 5:00 am on day 28 | 
| Blood Phe after administration of PKU GOLIKE and after amino acid protein substitute collected before breakfast |  | At 6:00 am on day 6 | 
| Blood Phe after administration of PKU GOLIKE and after amino acid protein substitute collected before breakfast |  | At 6:00 am on day 7 | 
| Blood Phe after administration of PKU GOLIKE and after amino acid protein substitute collected before breakfast |  | At 6:00 am on day 27 | 
| Blood Phe after administration of PKU GOLIKE and after amino acid protein substitute collected before breakfast |  | At 6:00 am on day 28 | 
| Blood Phe after administration of PKU GOLIKE and after amino acid protein substitute collected before breakfast |  | At 7:00 am on day 6 | 
| Blood Phe after administration of PKU GOLIKE and after amino acid protein substitute collected before breakfast |  | At 7:00 am on day 7 | 
| Blood Phe after administration of PKU GOLIKE and after amino acid protein substitute collected before breakfast |  | At 7:00 am on day 27 | 
| Blood Phe after administration of PKU GOLIKE and after amino acid protein substitute collected before breakfast |  | At 7:00 am on day 28 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dosage of Tyr in blood (umol/L) with dried blood spots before breakfast |  | At 5:00, 6:00, 7:00 am on day 6,7,27,28 | 
| Dosage of blood branch chain amino acids (BCAA)(umol/L) before breakfast |  | At 5:00, 6:00 and 7:00am on day 6,7,27,28 | 
| Dosage of Urea (mmol/L) and creatinine (umol/L) in urine |  | Days 0, 7, 21 and 28 | 
| Questionnaire on usual sleep habits | Questionnaire with open questions | Day 0, 7,21,28 | 
| Palatability questionnaire on days 7 or 28 | Questionnaire with questions on product palatability | Day 7 and 28 |