Plain English Summary
Background and study aims
Phenylketonuria (PKU) is an inherited disorder where the body can't break down the amino acid phenylalanine (phe), which then builds up in the blood and brain. This can lead to brain damage, organ damage and unusual posture, if not correctly diagnosed and no suitable nutritional management is started. As phe is an essential amino acid, the goal of nutritional management of PKU patients is to maintain adequate phe levels to support growth, normal brain development and mental functioning while providing a nutritionally complete diet and preventing neurological and psychological changes. Thus, patients with PKU require lifelong adherence to a low-phe diet that is restricted in natural foods, in order to limit the intake of natural protein and, at the same time, to provide adequate amounts of phe, in addition to the intake of phe-free protein substitutes to meet their protein needs. The aim of this study is to assess the acceptability and tolerability of a new protein substitute for the nutritional management of patients with phenylketonuria, aged 3-16 years. The outcome of this assessment will be used in a submission to regulatory authorities to get the study product reimbursable on prescription in the UK. The study product (PKU GOLIKE PLUS 3-16) is a phe-free protein substitute for the dietary management of children with PKU, aged 3-16 years. Specifically, the study product is an amino acid mixture engineered with a modified-release technology (Physiomimic technology), containing 17 amino acids, vitamins, minerals, other nutrients and two food additives forming a coating layer. The coating can mask the typical taste and odour of the amino acids. This coating is also able to provide a gradual release (prolonged release over time) of the amino acids from the formulation, in order to mimic more closely the absorption of amino acids from natural protein intake from food.
Who can participate?
Male and female patients with PKU, aged 3-16, who are already taking a protein substitute in addition to appropriate nutritional management.
What does the study involve?
At the first visit, participants are asked to replace their protein substitute with the study product (PKU GOLIKE PLUS 3-16). The treatment with the study product lasts for 7 days. As the study product contains vitamins and minerals, no supplementation is required. The last visit takes place at the end of the treatment period (day 7). During this time, caregivers are asked to complete a daily questionnaire recording information on patient’s compliance and any issues with administration and any gastro-intestinal side-effects. Additional questions are completed at the end of the study that consider perceptions about taste, appearance, smell, presentation and packaging of the product, ease of administration, and how it is taken. At both visits, participants are asked to undergo routine biochemical blood spot testing for phenylalanine and tyrosine in fasting conditions, for measuring blood phenylalanine levels. In the study, the product prescription is specified on an individual basis by the metabolic dietitian responsible for the patients’ nutritional management and is dependent on age and weight of the patient, but wholly replaces their currently prescribed protein substitute.
Where are the possible benefits and risks of participating?
A lot of protein substitutes are already available. However, compliance with taking protein substitutes continues to be a challenge. As a low protein diet is recommended for life, long-term compliance is a growing concern. As a result, improving the choice in terms of product type may aid compliance.
For PKU patients, this phe-free amino acid mixture engineered with a modified-release technology (Physiomimic technology), PKU GOLIKE PLUS 3-16, can represent a new option for the dietary management of this metabolic disease. Due to the coating covering the amino acids, the typical taste and odour of the amino acids are masked, and the release and consequent absorption of the amino acids is prolonged over time, to mimic more closely the absorption of amino acids from natural protein intake from food. These aspects, together with the opportunity to take this new protein substitute with non-hot beverages and foods with a creamy consistency as well, without modifying the taste of natural food, could improve patients’ compliance and adherence to diet and the whole nutritional management of PKU patients. Potential risks of the study may include refusal to take the product resulting in higher levels of phenylalanine (phe) in their blood. However, this risk will be minimised as the patient will be monitored clinically. If participants refuse to take the product for 24 hours, they will return to their normal protein substitute (i.e. the one used before entering the study) to ensure no harm is done to the child. Occasionally, different protein substitutes may cause abdominal pain, vomiting or diarrhoea, particularly if not taken with sufficient fluid. If there are any problems with tolerance children can stop the market research at any time on request of parents/caregivers or health care professionals or at the Lead Dietitian's discretion.
Where is the study run from?
Birmingham Women’s and Children NHS Foundation Trust (UK)
When is the study starting and how long is it expected to run for?
September 2018 to September 2019
Who is funding the study?
APR Applied Pharma Research sa, Balerna (Switzerland)
Who is the main contact?
Anna Barassi
anna.barassi@apr.ch
Trial website
Contact information
Type
Scientific
Primary contact
Mrs Anna Barassi
ORCID ID
Contact details
via Corti 5
Balerna
6828
Switzerland
+41 (0)91 6957020
anna.barassi@apr.ch
Additional identifiers
EudraCT number
Nil known
ClinicalTrials.gov number
Nil known
Protocol/serial number
APR/MF/02/2018
Study information
Scientific title
PKU GOLIKE PLUS 3-16 – Acceptability and Tolerance Market Research Study
Acronym
Study hypothesis
This is a prospective, observational market research study that aims at evaluating the acceptability and tolerability of a new protein substitute for the nutritional management of patients with phenylketonuria, aged 3-16 years.
The outcome of this assessment will be used in a submission to regulatory authorities to get the study product reimbursable on prescription in the UK.
Ethics approval
Approved 25/06/2019, West Midlands - Solihull Research Ethics Committee (The Old Chapel, Royal Standard Place, Nottingham, NG1 6FS, UK; Tel: +44 (0)207 1048191; Email: NRESCommittee.WestMidlands-Solihull@nhs.net), REC ref: 19/WM/0151
Study design
Prospective single-arm observational study
Primary study design
Observational
Secondary study design
Cohort study
Trial setting
Hospitals
Trial type
Treatment
Patient information sheet
Not available in web format; please, use contact details to request a participant information sheet.
Condition
Phenylketonuria
Intervention
The study product (PKU GOLIKE PLUS 3-16) is a phenylalanine-free protein substitute for the dietary management of patients with PKU, aged 3-16 years. Specifically, it is an amino acid mixture engineered with a modified-release technology (Physiomimic technology), containing 17 AAs, vitamins, minerals, other nutrients and two food additives forming a coating layer that modifies the organoleptic features of the product. The coating can indeed mask the typical taste and odour of the amino acids. This coating is also able to provide a gradual release (prolonged release over time) of the amino acids from the formulation, in order to mimic more closely the physiological absorption of amino acids from natural protein intake from food. In the study, the product prescription will be specified on an individual basis by the metabolic Dietitian responsible for the patients’ nutritional management and will be dependent on age and body weight of the patient, but will wholly replace their currently prescribed protein substitute.
The study involves 8-10 patients with phenylketonuria, aged 3-16 years, who are already taking a protein substitute in addition to appropriate nutritional management.
Two visits are foreseen. At the first visit, all subjects will be asked to replace their protein substitute with the study product (PKU GOLIKE PLUS 3-16). The treatment with the study product will last for 7 days. As the study product contains vitamins and minerals, no supplementation is required. The last visit will be performed at the end of the treatment period (day 7).
During this time, caregivers will be asked to complete a daily questionnaire recording information on patient’s compliance, any issues with administration, and any gastro-intestinal side-effects. Additional questions will also be completed at the end of the study that will consider perceptions about taste, appearance, smell, presentation and packaging of the product; ease of administration; and how it is taken. At both visits, subjects will be asked to undergo routine biochemical blood spot testing for phenylalanine and tyrosine, in fasting conditions, for measuring blood phenylalanine levels.
Intervention type
Other
Phase
Drug names
Primary outcome measure
1. Product acceptability (ease of use and palatability, i.e. perceptions about taste, appearance, smell) assessed using a questionnaire at day 7, at the end of the treatment
2. Product tolerability assessed using a questionnaire collecting data about gastro-intestinal side effects (i.e. diarrhoea, constipation, nausea, vomiting, abdominal pain) on a daily basis during the 7-day treatment
Secondary outcome measures
1. Compliance with the study product assessed using standardized questionnaires where the actual number of intakes versus prescribed intakes are recorded on a daily basis during the 7-day treatment
2. Metabolic control evaluated by measuring fasting blood phenylalanine levels by routine biochemical blood spot testing for phenylalanine and tyrosine at the beginning and at the end of the trial
Overall trial start date
15/09/2018
Overall trial end date
30/09/2019
Reason abandoned (if study stopped)
Eligibility
Participant inclusion criteria
1. Male and female patients with a diagnosis of phenylketonuria, aged 3-16 years
2. Subjects who are already taking a protein substitute for PKU and are willing to try the study product for 7 days
3. Written informed consent obtained from parental caregiver
Participant type
Patient
Age group
Child
Gender
Both
Target number of participants
Target number of PKU patients: 8-10
Participant exclusion criteria
1. Presence of serious concurrent illness
2. Lead Dietitian's uncertainty about the willingness or ability of the patient to comply with the protocol requirements
3. Participation in any other studies involving investigational or marketed products concomitantly or within two weeks prior to entry into the study
4. Any children having taken antibiotics over the previous 2 weeks leading up to the study
5. Children aged less than 3 years
Recruitment start date
15/06/2019
Recruitment end date
30/08/2019
Locations
Countries of recruitment
United Kingdom
Trial participating centre
Birmingham Women’s and Children NHS Foundation Trust
PI: Prof. Anita MacDonald
Dietetic Department
Steelhouse Lane
Birmingham
B4 6NH
United Kingdom
Sponsor information
Organisation
APR Applied Pharma Research SA
Sponsor details
via Corti 5
Balerna
6828
Switzerland
+41 (0)91 6957020
anna.barassi@apr.ch
Sponsor type
Industry
Website
Funders
Funder type
Industry
Funder name
APR Applied Pharma Research SA
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Results and Publications
Publication and dissemination plan
Data of the clinical study could be published in a journal as soon as the final study report is finalized. Data could be disseminated as abstract/poster or oral presentation in international scientific congresses.
IPD sharing statement
The datasets generated during and/or analysed during the current study are not expected to be made available. They will be included as appendices to the Clinical Study Report (CSR) and will be submitted to the Research Committee and to ACBS. They will be available in case an inspection from an Health Authority is foreseen.
Intention to publish date
30/09/2020
Participant level data
Not expected to be available
Basic results (scientific)
Publication list