Evaluation of TYR Sphere in France (TYR sphere Fra)

An Acceptability Study to Evaluate the Adherence, Tolerance and Metabolic Control of Patients With Tyrosinaemia When Using TYR Sphere (a Food for Special Medical Purposes) as Part of Dietary Management.

10 participants aged 3 years and over with tyrosinaemia or alkaptonuria will be prescribed Tyr sphere following an assessment of their individual needs by their dietitian.

All participants will enter a 4-week evaluation period, assessing adherence and gastrointestinal tolerance. Evaluations of Tyr sphere's palatability are made at the end of the evaluation period. Dried blood spots are taken on days 1 and 28 and once per week in between.

Participants who continue to take the product at the end of their evaluation period will enter a follow-up period during which metabolic control, anthropometric and nutritional status data will be collected during the yearly standard of care routine visits.

Study Overview

• Status: Active, not recruiting
• Conditions: Tyrosinemia; AKU
• Intervention / Treatment: Dietary supplement: Tyr sphere

Detailed Description

10 participants with tyrosinaemia or alkaptonuria will be invited to participate in this study. Following consent they will be assessed by their dietitian and a recommended amount of Tyr sphere will be prescribed based on their individual needs. Tyr sphere is a food for special medical purposes as defined by Regulation (EU) No 609/2013. It is designed to be prescribed based on its protein content, not its energy content.

Visit 1, baseline clinic visit activities: consent, demographics, anthropometric measurements, gastrointestinal history, dietary assessment, metabolic control assessment including collection of dried blood spots for phenylalanine and tyrosine levels, record routinely taken urine succinylacetone, serum albumin and pre-albumin levels, new dietary prescription.

Weeks 1 to 4 (patient at home): dried blood spots, adverse events reporting/assessment, daily Tyr sphere adherence diary, daily gastrointestinal symptoms diary (weeks 1 and 4 only), daily intake diary for Nitisinone which is routinely prescribed. There will be a telephone call

Visit 2, end of acceptability phase clinic visit activities: anthropometric measurements, review of diaries, review of adverse events, metabolic control assessment including collection of dried blood spots for phenylalanine and tyrosine levels, investigator's assessment of Tyr sphere for the participant and decision on continuing with the prescription.

Three-year routine follow-up: for the participants that do continue with the Tyr sphere prescription (in consultation with the investigator), they will enter a follow-up period of three years, during which only routine, standard of care visits and procedures will take place. Data will be collected on anthropometrics, phenylalanine and tyrosine levels from dried blood spots, adverse events, record routinely taken urine succinylacetone, serum albumin and pre-albumin levels.

• Study Type: Interventional
• Enrollment (Actual): 14
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Kirsten Imbert; Phone Number: +33 (0) 6 73 86 02 23; Email: Contact@Kirsten-Clinical-Research.com
• Study Contact Backup: Name: Clinical Trials Vitaflo; Phone Number: +44 (0) 151 709 90; Email: ClinicalTrialsTeam@Vitaflo.co.uk

Study Locations

• France
  • Paris, France
    • Hopital Necker-Enfants Malades

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 3 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Diagnosed with tyrosinaemia.
• Aged ≥ 3 years.
• In the opinion of the Investigator, can comply with the study protocol and take at least one sachet of the study product per day.
• Willingly given, written, informed consent from patient or parent/guardian.
• Willingly given, written assent (if appropriate).

Exclusion Criteria:

• Individuals who are allergic to milk, fish and soya (these allergens are inherent in the study product ingredients).
• Use of additional macro/micronutrient supplements during the evaluation period, unless clinically indicated and prescribed by the Investigator (must be recorded in patient case report form CRF).
• Women who are pregnant / breastfeeding at the start of the study or planning to become pregnant during the study.

N.B.: Women who become pregnant during the study will no longer be able to participate and will be withdrawn.

• Individuals who, in the opinion of the investigator, are unable to comply with the requirements of the protocol.
• Any co-morbidity, which, in the opinion of the Investigator, would preclude participation in the study.
• Patients who are currently participating in, plan to participate in, or have participated in an interventional investigational drug, food or medical device trial within 30 days prior to screening visit.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Tyr sphere; All patients to receive Tyr sphere as part of their dietary management for tyrosinaemia or alkaptonuria (AKU).

Dietary supplement: Tyr sphere; Tyr sphere is a powdered, low phenylalanine and tyrosine protein substitute, containing a balanced mix of casein glycomacropeptide (cGMP) isolate, essential and non-essential amino acids, carbohydrate, fat, vitamins, minerals and the long chain polyunsaturated fatty acid (LCP) and docosahexaenoic acid (DHA). It contains sugars and sweetener. The product is designed to be prescribed based on its protein content, not its energy content.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in adherence to recommended amounts of Tyr sphere	Patient reported data on actual compared to prescribed intakes of Tyr sphere, assessed by HCPs periodically as per routine practice.	Recorded daily on days 1-28
Change in gastrointestinal tolerance	Patient reported data on any gastrointestinal symptoms experienced, assessed by HCPs periodically as per routine practice.	Recorded daily on days 1-28
Patient evaluation of Tyr sphere's palatability	Patient-reported assessment of Tyr sphere's palatability on a Likert scale: 1 (really didn't like it) to 5 (loved it).	Day 28, end of acceptability phase
Change in metabolic control: tyrosine levels	Tyrosine levels obtained from dried blood spots	Day 1, week 1, week 2, week 3, week 4, day 28
Change in metabolic control: phenylalanine levels	Phenylalanine levels obtained from dried blood spots	Day 1, week 1, week 2, week 3, week 4, day 28

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Long term change in growth	Recorded progress in growth from standard of care follow-up visits for three years	3-year follow-up period
Long term change in urine succinylacetone level	Recorded changes in urine succinylacetone levels from standard of care follow-up visits for three years	3-year follow-up period
Long term change in pre-albumin level	Recorded changes in pre-albumin levels from standard of care follow-up visits for three years	3-year follow-up period
Long term change in serum albumin level	Recorded changes in serum albumin levels from standard of care follow-up visits for three years	3-year follow-up period

Collaborators and Investigators

• Sponsor: Vitaflo International, Ltd
• Investigators: Principal Investigator: Jean-Baptiste Arnoux, Hopital Necker-Enfants Malades

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2021
• Primary Completion (Estimated): December 31, 2024
• Study Completion (Estimated): January 31, 2025

Study Registration Dates

• First Submitted: February 15, 2021
• First Submitted That Met QC Criteria: February 15, 2021
• First Posted (Actual): February 21, 2021

Study Record Updates

• Last Update Posted (Actual): February 15, 2024
• Last Update Submitted That Met QC Criteria: February 14, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: Alkaptonuria; Tyrosinemia; Food for special medical purposes; AKU; Tyr Sphere; FSMP
• Additional Relevant MeSH Terms: Metabolic Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Genetic Diseases, Inborn; Metabolism, Inborn Errors; Brain Diseases, Metabolic; Brain Diseases, Metabolic, Inborn; Amino Acid Metabolism, Inborn Errors; Tyrosinemias
• Other Study ID Numbers: TyrSph-2020-10-16; SI 21.01.06.74121 (Other Identifier: CPP Est I); 2021-A01263-38 (Other Identifier: REC)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No