Evaluating the Efficacy of PKU Synergy in Patients Expressing Phenylketonuria or Hyperphenylalaninemia

Study Overview
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Brief Summary
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This study centres around a new one-a-day phenylalanine-free protein substitute for phenylketonuria patients. Fifty eligible adults (≥ 16 years) with proven phenylketonuria or hyperphenylalaninemia will be recruited and randomly allocated to one of two intervention arms (n = 25 per arm). Following a 3-day baseline period, and in addition to routine nutritional management, patients will receive either one sachet of the new protein substitute daily (intervention) or continue their usual dietary and/or protein substitute regimen (maximum of 1 protein substitute per day (equal to 20g protein equivalent) control) for 28 days.

Detailed Description
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This study centres around a new one-a-day phenylalanine-free protein substitute for phenylketonuria patients. In particular, this randomised controlled trial aims to evaluate the efficacy (changes relating to nutritional status and metabolic control) of this new protein substitute, while also capturing data pertaining to tolerance, compliance, safety and acceptability. Designed for poorly compliant adult patients with proven phenylketonuria or hyperphenylalaninemia, this new protein substitute is composed of an adapted mixture of other essential and non-essential amino acids, carbohydrates, vitamins and selected minerals and trace elements and enriched with docosahexaenoic acid (DHA). Fifty eligible adults (≥ 16 years) will be recruited and randomly allocated to one of two intervention arms (n = 25 per arm). Following a 3-day baseline period, and in addition to routine nutritional management, patients will receive either one sachet of the new protein substitute daily (intervention) or continue their usual dietary and/or protein substitute regimen (maximum of 1 protein substitute per day (equal to 20g protein equivalent) control) for 28 days.

Official Title
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Evaluating the Efficacy of PKU Synergy in Patients Expressing Phenylketonuria or Hyperphenylalaninemia

Conditions
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Phenylketonurias, Hyperphenylalaninaemia, Type I

Intervention / Treatment
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* Dietary Supplement: Synergy
* Other: Routine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female Over 16 years of age Diagnosed with proven PKU or hyperphenylalaninemia with an increased phenylalanine-tolerance/intake Currently taking a maximum of 1 protein substitute per day (equal to 20g protein equivalent) Have a minimum blood phenylalanine level of ≥ 600 umol/L (for PKU patients) Have relaxed (if not stopped) their dietary and protein substitute regimen for at least 1 month prior to trial commencement Have Written informed consent from patient Exclusion Criteria: Pregnant or lactating Requiring nutritional support (including enteral and parenteral nutrition) Major hepatic or renal dysfunction Participation in other studies within 1 month prior to entry of this study Allergy to any of the study product ingredients, including milk protein or soya Investigator concern around willingness/ability of patient to comply with protocol requirements

Ages Eligible for Study
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Minimum Age: 16 Years
Maximum Age: 100 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: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Synergy<br>This group will receive the new phenylalanine-free protein substitute daily for 28 days. Patients in this group intervention will be directed to consume one powder sachet (33 g) of daily made up with 100mL of water. The new substitute delivers 414 kJ, 20g protein equivalent and a combination of essential and non-essential amino acids as well a combination of vitamins and minerals. | Dietary Supplement: Synergy<br>* Small serving (x1 33 g serving daily) of the new phenylalanine-free protein substitute made up with 100mL of water daily (28 days).<br>|
| Active Comparator: Routine<br>This group will continue their usual dietary and/or protein substitute regimen (maximum of 1 protein substitute per day (equal to 20g protein equivalent) control) for 28 days. | Other: Routine<br>* Patients will continue their usual dietary and/or protein substitute regimen (28 days).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Nutritional Status (objective measure) | Blood micro nutrient levels; active Vitamin B12 (holotranscobalamin) | 2 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Nutritional Status (Objective measure) | Blood micro nutrient levels; Folate (Folic Acid) | 2 days | 
| Nutritional Status (Objective measure) | Blood micro nutrient levels; Iron (Ferritin) | 2 days | 
| Nutritional Status (Objective measure) | Blood micro nutrient levels; Zinc | 2 days | 
| Nutritional Status (Objective measure) | Blood micro nutrient levels; Vitamin D (25-hydroxyvitamin D) | 2 days | 
| Nutritional Status (subjective measure) | 3 day weighed food diary | 6 days | 
| Daily compliance with prescribed protein substitute as assessed by standarised questionnaire | Compliance with the recommended intake of the patients previously prescribed protein substitute (during baseline in both groups, and during the study period in the control group) and with the study product during the intervention period will be assessed daily throughout the study. Patients will be asked to record how much of the protein substitute is taken compared to that recommended by their Health Care Professional. The daily amount prescribed by the Health Care Professional managing the patients care will be recorded at the start of the study and any changes to this prescription during the study will be noted. During the intervention period, protein substitute consumption patterns (e.g. timing and amount consumed) will be recorded daily and assessed b y a standardised questionnaire. | 31 days | 
| Metabolic Control | Blood amino acid levels; Collected samples will be analysed for blood phenylalanine, tyrosine and 16 other proteinogenic amino acids, 2 non-proteinogenic amino acids and 1 amino sulfonic acid. | 2 days | 
| Gastrointestinal tolerance as assessed by standarised questionnaire | Gastrointestinal tolerance (including diarrhoea, constipation, nausea, vomiting, abdominal pain, bloating, flatulence and burping) will be assessed using a standardised gastrointestinal tolerance questionnaire completed by the patient. | 12 days | 
| Acceptability as assessed by standarised questionnaire | Acceptability (ease of use and liking) of the patients previously prescribed protein substitute and the study product will be assessed at the end of baseline (day 4) and the end of the intervention period (day 31) using a standardised questionnaire completed by the patient. | 2 days | 
| Subjective Mood | Profile of mood states questionnaire | 3 days | 
| Anthropometry | Measures of weight and height will be made during baseline observations (day 1) and at the end of the intervention period (day 31). Weight will be determined to the nearest 0.1 kg, using portable scales shoeless and wearing light weight clothing. | 2 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Phenylketonuria, Hyperphenylalaninaemia, Inherited Metabolic Disorders