Glytactin EfficiEncy in Non or Insufficiently Treated Adult PHENylketonuria Patients (GLEEPHEN)

Phenylketonuria is the most common inherited metabolic disease in France and is screened for neonatal exposure. Management consists of a strict and restrictive hypoproteic diet and the intake of amino acid substitutes and dietary supplements free of phenylalanine.One of the major difficulties, which is the source of many treatment failures, is the inappetence of the amino acid supplements required during a strict hypoproteic diet. New formulations, Glycomacropeptides (GMP), have recently appeared and are considered more palatable than conventional amino acid mixtures.

Study Overview

• Status: Completed
• Conditions: Adult Phenylketonuria Non Treated Patients
• Intervention / Treatment: Dietary supplement: Dietary Supplement for PKU patients

Detailed Description

Phenylketonuria is the most common inherited metabolic disease in France and is screened for neonatal exposure. Management consists of a strict and restrictive hypoproteic diet and the intake of amino acid substitutes and dietary supplements free of phenylalanine. If the benefits of treatment are indisputable in children in terms of cognitive prognosis, this benefit is discussed once brain development is complete, especially as many adult patients are no longer treated. However, cognitive, neurological and reversible white matter disorders undergoing treatment are increasingly reported in adult phenylketonurics. As a result, recent European recommendations advocate the maintenance of life-long treatment. One of the major difficulties, which is the source of many treatment failures, is the inappetence of the amino acid supplements required during a strict hypoproteic diet. New formulations, Glycomacropeptides (GMP), have recently appeared and are considered more palatable than conventional mixtures.

PRIMARY OBJECTIVE:

Demonstrate a better metabolic balance under GMP treatment than a conventional amino acid mixture in adult phenylketonuric patients when resuming treatment.

• Study Type: Interventional
• Enrollment (Actual): 13
• Phase: Not Applicable

Contacts and Locations

Study Locations

• France
  • Angers, France, 49933
    • CHU-ANGERS -Médecine Interne
  • Brest, France, 29609
    • CHU du Morvan-Département de Pédiatrie et génétique médicale,
  • Bron, France, 69677
    • Hôpital Femme-Mère-Enfant-Centre de Référence des Maladies Héréditaires du Métabolisme de Lyon
  • Lille, France, 59037
    • CHU de LILLE-Hôpital Claude HURIEZ-Service d'Endocrinologie
  • Nantes, France, 44000
    • CHU-Service de Réanimation Pédiatrique / Néonatalogie, Consultation spécialisée en Maladies Héréditaires du Métabolisme
  • Rennes, France, 35203
    • CHU-RENNES-Hôpital Sud-Service de Génétique-Clinique
  • Centre
    • Tours, Centre, France, 37044
      • CHRU-Hôpital Bretonneau - Service de Médecine Interne-Nutrition

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patient age ≥18 years on an empty stomach
• Phenylketonuric patient Patient with Phenylalaninemia ≥ 900μmol / L on a blotter performed during the screening period (or average of blotter results ≥900 μmol / L if several blotters performed during the screening period)
• Untreated or insufficiently treated patient: not taking or insufficiently Dietary foods for special medical purposes for his PKU, regardless of diet, at the discretion of the investigator
• Patient having signed a free, informed and express consent
• Patient requiring a diet restricted in natural proteins

Exclusion Criteria:

• Protected patient: court bail
• Patient with concomitant diseases / conditions that may compromise the study, at the discretion of the investigator
• Participated in a clinical trial or trial to evaluate PKU foods or treatments in the last 7 days prior to inclusion or planned during the next 6 months
• Participation in an interventional study with health products during the next 6 months
• Pregnancy project within 6 months, pre-conception diet, pregnancy or breastfeeding
• Refusal to consume only validated complements for the protocol
• Phenylketonuria undergoing treatment with BH4
• Allergy to the product under study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: GMP - Dietary Supplement for PKU patients; Glycomacropeptides -GMP Glytactin	Dietary supplement: Dietary Supplement for PKU patients; For both treatment groups, the objective in total protein will be 1g / kg / day of ideal weight, in 3-6 doses / day, including natural proteins and supplemented by the products under study.
Active Comparator: Control -Amino acids mixtures; Mixtures of conventional amino acids.	Dietary supplement: Dietary Supplement for PKU patients; For both treatment groups, the objective in total protein will be 1g / kg / day of ideal weight, in 3-6 doses / day, including natural proteins and supplemented by the products under study.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of phenylalaninemia on blotter	Rate of phenylalaninemia on blotter measured bi-monthly during the 6 months of the study.	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Therapeutic compliance	Therapeutic compliance measured after 3 months and 6 months of treatment	6 months
Evolution of neuropsychological tests	Neuropsychological tests measured after 3 months and 6 months of treatment	6 months
MRI brain M0, M6 evolution	MRI brain evolution between inclusion and 6 months of treatment	6 months
Bone remodeling markers	Bone remodeling markers at inclusion and 6 months of treatment	6 months
Evolution of quality of life (PKU QoL score), mood (POMS test - Fillion 1999), at M0, M3, M6.	Evolution of quality of life scores at inclusion, 3 months and 6 months of treatment	6 months
Nutritional and clinical markers evaluated at inclusion and 6 months of treatment	Evolution of nutritional and clinical markers at inclusion and 6 months of treatment	6 months
Gastrointestinal tolerance at M3 and M6	Evolution of Gastrointestinal tolerance after 3 months and 6 months of treatment	6 months

Collaborators and Investigators

• Sponsor: University Hospital, Tours
• Investigators: Study Director: Adrien BIGOT, MD-PHD, University hospital of Tours

Study record dates

Study Major Dates

• Study Start (Actual): September 19, 2019
• Primary Completion (Actual): March 14, 2022
• Study Completion (Actual): September 5, 2022

Study Registration Dates

• First Submitted: April 22, 2019
• First Submitted That Met QC Criteria: April 22, 2019
• First Posted (Actual): April 23, 2019

Study Record Updates

• Last Update Posted (Actual): September 21, 2022
• Last Update Submitted That Met QC Criteria: September 20, 2022
• Last Verified: September 1, 2022

More Information

Terms related to this study

• Keywords: PKU; GMP; Amino acid
• 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; Phenylketonurias
• Other Study ID Numbers: DR180127 - GLEEPHEN; 2018-A03244-51 (Registry Identifier: IRCB)

Drug and device information, study documents

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