Compliance, Tolerance and Acceptability of a Tablet Protein Substitute for the Dietary Management of Phenylketonuria

March 11, 2019 updated by: Nutricia UK Ltd
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.

Study Overview

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.

Study Type

Interventional

Phase

  • Not Applicable

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

8 years to 100 years (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Supportive Care
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Intervention
Intervention is phenylalanine-free protein substitute. Following a 7 day baseline period, all recruits will receive the new phenylalanine-free protein substitute daily for 28 days in addition to routine nutritional management. The study product prescription will be specified on an individual basis by the metabolic Dietitian responsible for the patient's nutritional management and will be dependent on age, bodyweight and medical condition of the patient, but will wholly replace their currently prescribed tablet protein substitute and multivitamin supplements.
Thirty eligible PKU patients (≥ 8 years), identified as current tablet users, will be recruited to this study. Patients will firstly observe a 7-day baseline period. During baseline, patients will continue with their existing diet and protein substitute prescription before receiving Phenylalanine-free protein subsitute tablets daily for 28 days in addition to appropriate nutritional management.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Daily Compliance
Time Frame: 35 days
Compliance with currently prescribed protein substitute and prescribed multivitamin supplements will be assessed daily from days 1-7 and recorded as a percentage of tablets consumed comapred to prescription (0-100%). Compliance with the study product will subsequently be assessed daily from days 8-35. Compliance throughout the trial will be assessed using standarised questionnaires, where patients document number of med versus number of tablets prescribed. A percentage compliance level based on per patient and total patients will be computed to define overall compliance where a higher percentage represents better overall compliance.
35 days

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Treatment-Emergent tolerability
Time Frame: 12 days
Gastrointestinal tolerance (including diarrhoea, constipation, nausea, vomiting, abdominal pain, bloating, flatulence and burping) will be assessed via questionnaire using the scale (absent, mild, moderate, severe).
12 days
Patient Acceptability
Time Frame: 2 days
Acceptability (ease of use and palatability) will be assessed via questionnaire.
2 days
Metabolic control
Time Frame: 2 days
Blood phenylalanine, blood tyrosine and other amino acids. Fingertip-capillary blood samples will be collected in the fasted state at baseline observations (day 1), and on the last day of the intervention period (day 35). 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
Nutritional Intake
Time Frame: 2 days
To assess habitual dietary intake, 24 hour dietary recalls will be completed during baseline and at the end of the intervention period.
2 days
Weight
Time Frame: 2 days
Measures of weight (kg) will be made during baseline observations and at the end of the intervention period.
2 days
Height
Time Frame: 2 days
Measures of weight (kg) will be made during baseline observations and at the end of the intervention period.
2 days
Incidence of study product emergent adverse events [safety].
Time Frame: Baseline
All adverse events will be recorded throughout the study (as and when they occur). Consequently, there is no specific time frame as the frequency of adverse events can not be predicted.
Baseline

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Investigators

  • Study Director: Rebecca Stratton, PhD, Nutricia, Inc.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Anticipated)

July 15, 2019

Primary Completion (Anticipated)

December 30, 2019

Study Completion (Anticipated)

December 31, 2019

Study Registration Dates

First Submitted

September 18, 2017

First Submitted That Met QC Criteria

November 2, 2017

First Posted (Actual)

November 7, 2017

Study Record Updates

Last Update Posted (Actual)

March 13, 2019

Last Update Submitted That Met QC Criteria

March 11, 2019

Last Verified

March 1, 2019

More Information

Terms related to this study

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

IPD Plan Description

No IPD will be shared with other researchers.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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