Clinical trial NCT03333720: Compliance, Tolerance and Acceptability of a Tablet Protein Substitute for the Dietary Management of Phenylketonuria
Official title: Compliance, Tolerance and Acceptability of a Tablet Protein Substitute for the Dietary Management of Phenylketonuria
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: NA
Conditions: Phenylketonurias
Keywords: Phenylketonuria
Inherited Metabolic Disorders
Lead sponsor: Nutricia UK Ltd
Sponsor class: INDUSTRY
First posted: 2017-11-07
Enrollment: 0
Sex: ALL
Minimum age (years): 8
Maximum age (years): 100
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: SUPPORTIVE_CARE

Brief summary: Thirty eligible PKU patients (≥ 8 years), identified as tablet protein substitute users, will be recruited. Patients will firstly observe a 7-day baseline period, in which participants will continue with their existing diet, protein substitute and multi vitamin prescription. Patients will then receive the phaenylalanine-free protein substitute tablets daily for 28 days in addition to appropriate nutritional management. The aim of this prospective, single arm trial is to evaluate the acceptability (compliance, tolerance and palatability) of the phenylalanine-free protein substitute tablets in patients with proven PKU. The primary outcome measure is compliance, with secondary outcome measures of gastrointestinal tolerance, acceptability, blood amino acids, dietary intake, anthropometry and safety.

Detailed description: Protein substitutes are typically presented in powder format and reconstituted in water to a set volume, but may also be offered in ready-to-drink formats or as a gel. Notwithstanding recent advancements related to the taste, scent and texture (organoleptic properties) of commercially available protein substitutes, a small proportion of PKU patients choose to consume tablet-based protein substitutes. In this sense, anecdotal evidence suggests that in the UK approximately 80-100 PKU patients consume tablet protein substitutes. Despite the need to consume large quantities, protein substitutes in tablet format may help overcome some of the aforementioned limitations compared to powdered or ready-to-drink preparations, but also offer additional benefits including convenience and reduced preparation.

Although usage of tablet-based protein substitutes is low in comparison to powdered preparations, early evidence from MacDonald and colleagues suggests tablet protein substitutes are an equally effective strategy to manage PKU in older children, teenagers and adults. Tablet-based protein substitutes, however, only offer a balanced mixture of essential and non-essential amino acids. Considering the daily burden and discipline required to follow the restrictive low-protein diet, reports suggest achieving full compliance with tablet-based protein substitutes is difficult, and this becomes especially challenging when given alongside multi vitamin supplements. To elaborate, patients solely consuming protein substitutes in tablet format may be required to consume 70-140 tablets per day (average = 75 tablets per day) alongside an additional 5 prescribable vitamin and mineral tablets. In this instance, it may be beneficial if tablet-based protein substitutes combined amino acids with vitamins, minerals and trace elements.

At present, tablets combining amino acids with vitamins, minerals and trace elements are currently unavailable. As such, the sponsor has produced a tablet-based protein substitute designed for individuals aged 8 years and older. Developed specifically for the dietary management of proven PKU, the phenylalanine-free protein substitute tablets comprise an adapted mixture of essential and non-essential amino acids (excluding phenylalanine) and are combined with carbohydrates, DHA, vitamins and selected minerals and trace elements. As such, the aim of this intervention trial is therefore to evaluate the acceptability (compliance, gastrointestinal tolerance and palatability) of the tablets, while also capturing information related to blood amino acid profiles, dietary intake, anthropometry and safety as part of a low phenylalanine dietary regimen in PKU patients. Thirty eligible PKU patients (≥ 8 years), identified as current tablet users, will be recruited. Patients will firstly observe a 7-day baseline period. During baseline, patients will continue with their existing diet and protein substitute prescription before receiving the tablets daily for 28 days in addition to appropriate nutritional management.

Eligibility criteria: Inclusion Criteria:

* Male or female
* 8 years of age and older
* Diagnosed with proven PKU
* Consume a minimum of 20g protein equivalent in tablet format while enrolled on to the trial
* If routine care and dietary management is not different from normal PKU care and dietary management, preconception patients may be considered
* Have written informed consent from patient or parent/carer carer

Exclusion Criteria:

* Requiring nutritional support (including enteral and parenteral nutrition)
* Major hepatic or renal dysfunction
* Maternal PKU patients (if a patient becomes pregnant during the study they will be withdrawn on immediate notice to the Metabolic Dietitian responsible for the patient's care)
* Participation in other studies within 1 month prior to entry of this study
* Investigator concern around willingness/ability of patient to comply with protocol requirements

Primary outcomes:
measure: Daily Compliance
timeFrame: 35 days
Secondary outcomes:
measure: Treatment-Emergent tolerability
timeFrame: 12 days
measure: Patient Acceptability
timeFrame: 2 days
measure: Metabolic control
timeFrame: 2 days
measure: Nutritional Intake
timeFrame: 2 days
measure: Weight
timeFrame: 2 days
measure: Height
timeFrame: 2 days
measure: Incidence of study product emergent adverse events [safety].
timeFrame: Baseline
Other outcomes:
Locations:
Study officials:
affiliation: Nutricia, Inc.
name: Rebecca Stratton, PhD
role: STUDY_DIRECTOR
References: