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GMP Case Studies of Tolerance, Safety and Acceptability in PKU and TYR

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ClinicalTrials.gov Identifier: NCT05062226
Recruitment Status : Recruiting
First Posted : September 30, 2021
Last Update Posted : September 30, 2021
Sponsor:
Information provided by (Responsible Party):
Nutricia UK Ltd

Brief Summary:

Three new protein substitutes have been developed to help with compliance in PKU and TYR patients, which are powdered protein substitutes, low in Phe and, low in Phe and Tyr respectively, with a mixed balance of glycomacropeptide (GMP), essential and non-essential amino acids, carbohydrates, fats and micronutrients for the dietary management of PKU and TYR.

This series of case-studies will evaluate the acceptability, compliance, gastrointestinal tolerance and safety of the three GMP-based products for PKU and TYR in 45 patients with PKU and TYR, in both adults and children over 3 years (15 patients per product). The case study will last 29 days in total, including a 1-day baseline period followed by a 28-day intervention period. The case studies will be conducted across multiple specialist metabolic centres in the UK, to meet the UK ACBS and GMS requirements for acceptability studies. A series of case studies is undertaken due to the rarity of these conditions and the difficulty in recruiting these patients to trials.


Condition or disease Intervention/treatment Phase
PKU Tyrosinemias Dietary Supplement: PKU/TYR GMP Protein Substitute Not Applicable

Detailed Description:

Phenylketonuria (PKU) and Tyrosinaemia (TYR) are rare inherited metabolic disorders of amino acid metabolism requiring dietary management. PKU is characterised by an inability to metabolise the essential dietary amino acid phenylalanine (Phe) into tyrosine (Tyr). As such, without appropriate management, PKU can lead to extremely elevated levels of Phe within the blood and brain, which can be detrimental to neurological health. The dietary management of PKU involves restricting dietary sources of Phe. Tyrosinaemia (TYR) is characterised by the inability to metabolise the dietary amino acid Tyr. If left uncontrolled, TYR can lead to serious hepatic, renal and neurological complications. The dietary management of TYR involves restriction of dietary sources of Tyr and Phe (as Phe is converted into Tyr). The dietary management of PKU and TYR involves restricting dietary protein intake to promote optimal metabolic control, whilst meeting all other amino acid and nutrient requirements. As Phe and Tyr are present in significant quantities in nearly all dietary proteins, this usually requires a very low protein diet from food, supplemented with a Phe-free (for PKU) or Phe- and Tyr-free (for TYR) amino acid-based protein substitute. However, compliance with the diet is often poor, with patients commonly going "off diet" during adolescence and in adulthood. This can lead to entirely preventable, lifelong mental and physiological impairments. Reasons for non-compliance often revolve around the strong taste of amino acid-based protein substitutes, alongside the inability to conform to the normal eating habits of peers.

Three new protein substitutes have been developed to help with compliance in PKU and TYR patients, which are powdered protein substitutes, low in Phe and, low in Phe and Tyr respectively, with a mixed balance of glycomacropeptide (GMP), essential and non-essential amino acids, carbohydrates, fats and micronutrients for the dietary management of PKU and TYR. The protein in GMP-based products for PKU and TYR are based on GMP, a peptide isolated from milk during cheese manufacturing and the only known naturally derived protein source low in Phe and Tyr. The GMP is supplemented with appropriate quantities of other amino acids which are naturally low or not present in GMP, as well as carbohydrates and fats. This differs from traditional formulae which are based wholly on individual, synthetically produced amino acids to provide the source of dietary nitrogen, supplemented with vitamins and minerals. Studies to date have illustrated that PKU patients who replace their regular Phe-free amino acid-based formula with GMP-based foods may have better diet compliance, prefer the taste and may have improved blood Phe control.

This series of case-studies will evaluate the acceptability, compliance, gastrointestinal tolerance and safety of the three GMP-based products for PKU and TYR in 45 patients with PKU and TYR, in both adults and children over 3 years (15 patients per product). The case study will last 29 days in total, including a 1-day baseline period followed by a 28-day intervention period. The case studies will be conducted across multiple specialist metabolic centres in the UK, to meet the UK ACBS and GMS requirements for acceptability studies. A series of case studies is undertaken due to the rarity of these conditions and the difficulty in recruiting these patients to trials.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 45 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description: 15 patients per product will be included in the case studies for a total of 45 patients.
Masking: None (Open Label)
Primary Purpose: Other
Official Title: Evaluating the Tolerance, Safety and Acceptability of GMP-based Protein Substitutes for the Dietary Management of Phenylketonuria and Tyrosinaemia in Children and Adults: a Case Study Series
Actual Study Start Date : September 16, 2020
Estimated Primary Completion Date : August 2022
Estimated Study Completion Date : December 2022


Arm Intervention/treatment
Experimental: GMP-based products
GMP-based nutritional protein substitutes for the dietary management of PKU and TYR
Dietary Supplement: PKU/TYR GMP Protein Substitute
After a 1-day baseline period during which patients will consume their usual protein substitute, each patient will receive one the case study product for 4 weeks (28 days).




Primary Outcome Measures :
  1. Acceptability [ Time Frame: Baseline (Day 1) - End of case studies (Day 29) ]
    Acceptability of the patients' usual protein substitute and the study product assessed by the Dietitian with a series of questions posed to the patient and/or parent/caregiver on on all attributes which included appearance, smell, taste, texture (mouthfeel), ease of mixing, ease of taking, after taste and smell of breath after taking, assessed on a 5-point likert scale (Great; Good; OK; Bad; Terrible).


Secondary Outcome Measures :
  1. Compliance [ Time Frame: Baseline (Day 1) - End of case studies (Day 29) ]
    Compliance (% intake compared to that prescribed) with the recommended intake of the patients' usual protein substitute (during baseline) and with the case study product (during the case study period) will be assessed by the Dietitian.

  2. Gastro-intestinal (GI) tolerance [ Time Frame: Baseline (Day 1) - End of case studies (Day 29) ]
    Gastro-intestinal (GI) tolerance symptoms will be recorded by the Dietitian.

  3. Anthropometry [ Time Frame: Baseline (Day 1) - End of case studies (Day 29) ]
    Body weight (kg) and height (m) will be measured where possible using standard methods to calculate body mass index (BMI)



Information from the National Library of Medicine

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Ages Eligible for Study:   3 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Male or female
  • Over 3 years of age
  • Diagnosed with classical or variant type phenylketonuria, or tyrosinaemia (as appropriate)
  • Have been compliant in taking at least one protein substitute, providing at least 10g protein equivalents, for at least 1 month prior to trial commencement
  • Have a prescribed daily Phe or Phe and Tyr allowance for PKU or TYR respectively
  • Written or electronic informed consent from patient, and/or from parent/caregiver if applicable

Exclusion Criteria:

  • Currently prescribed Sapropterin or similar tetrahydrobiopterin based medication
  • Pregnant or lactating
  • Requiring 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 and soy
  • Investigator concern around willingness/ability of patient or parent/caregiver to comply with protocol requirements

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05062226


Contacts
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Contact: Marta Delsoglio 07735819720 marta.delsoglio@nutricia.com
Contact: Gary Hubbard gary.hubbard@nutricia.com

Locations
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United Kingdom
Bristol University Hospitals Recruiting
Bristol, United Kingdom
Contact       researchapprovals@uhbw.nhs.uk   
Sponsors and Collaborators
Nutricia UK Ltd
Investigators
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Study Chair: Rebecca Stratton Nutricia UK Ltd
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Responsible Party: Nutricia UK Ltd
ClinicalTrials.gov Identifier: NCT05062226    
Other Study ID Numbers: GMP2020
First Posted: September 30, 2021    Key Record Dates
Last Update Posted: September 30, 2021
Last Verified: September 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Nutricia UK Ltd:
PKU
TYR
Additional relevant MeSH terms:
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Tyrosinemias
Brain Diseases, Metabolic, Inborn
Brain Diseases, Metabolic
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Amino Acid Metabolism, Inborn Errors
Metabolism, Inborn Errors
Genetic Diseases, Inborn
Metabolic Diseases