Study of Low-grade Systemic Inflammation in Adult Patients With Phenylketonuria (INGRAPH)
Etude de l'INflammation systémique de Bas GRade Chez Les Patients Adultes Atteints de PHénylcétonurie
Patient suffering from phenylketonuria have chronic hyperphenylalaninemia. Hyperphenylalaninemia is known to be toxic to central nervous system and cardiovascular system in particular through oxydative stress.
In this context, research of low grade systemic inflammation through cytokine assay appears legitimate.
The primary outcome of this study is to describe inflammation profile of patients with phenylketonuria.
Aperçu de l'étude
Description détaillée
Phenylketonuria (PKU) is a metabolic hereditary disease due to lack of activity of phenylalanine hydroxylase. This lack of activity whom origin is genetic, results in chronic hyperphenylalaninemia, toxic to central nervous system and cardiovascular system. Without treatment, PKU is responsible for mental retardation in children.
PKU is subject to systematic screening at birth and if diagnosis is confirmed a specific diet controlled in phenylalanine is prescribed for infant. This diet allows a neurodevelopment as closed as healthy infant. Despite this diet, neurological and systemic complications are more often reported at adult age. It is therefore recommended to follow patient regularly in order to search for those complications.
In a PKU murine model, it has been shown (cf references) that a low grade systematic inflammation exists and was reversible after dietetic treatment using glycomacropeptide (through a probiotic effect of this protein naturally phenylalanine free). Existence of this low grade systematic inflammation, evaluated by plasmatic cytokine screening (TNF alpha IL2, IL6, IL10, IFNgamma, IL1Alpha, IL1Beta and protein C reactive) has not been proven in humans to date.
Primary outcome of this study is to characterize this low grade systemic inflammation profile in patient with PKU.
Type d'étude
Inscription (Réel)
Phase
- N'est pas applicable
Contacts et emplacements
Lieux d'étude
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Tours, France, 37044
- Clinical investigation center, University Hospital, Tours
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Tours, France, 37044
- Internal Medicine Service, University Hospital, Tours
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Critères de participation
Critère d'éligibilité
Âges éligibles pour étudier
Accepte les volontaires sains
Sexes éligibles pour l'étude
La description
Inclusion Criteria (patient with PKU)
- Age >/= 18 years old
- Phenylketonuria diagnosis
- Fasting condition
- Registered with a social security system
- Patient consent
Inclusion Criteria (healthy volunteer)
- Age >/= 18 years old
- No metabolic condition
- Fasting condition
- Paired to patient with phenylketonuria already included according to age, sex and BMI class
- Registered with a social security system
- Volunteer consent
Exclusion Criteria, common to healthy volunteer and patient with phenylketonuria
- Pregnant and lactating women
- Subject to legal protection measures.
- Chronic or acute inflammatory disease
- Fever on inclusion
- Undergoing anti inflammatory treatment
- Surgery in the previous months
- Diabetes
- Included in other therapeutic trial
Plan d'étude
Comment l'étude est-elle conçue ?
Détails de conception
- Objectif principal: Dépistage
- Répartition: Non randomisé
- Modèle interventionnel: Affectation parallèle
- Masquage: Aucun (étiquette ouverte)
Armes et Interventions
Groupe de participants / Bras |
Intervention / Traitement |
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Autre: Healthy subject
The intervention, specific to the study, is to take blood samples on patients healthy volunteers. Healthy subject will be paired to patient with phenylketonuria according to body mass index and sex. |
Plasmatic cytokine and plasmatic CRP assay will be realised using luminex in both arms.
IL2, IL10,INF gamma, IL, IL6, ILB, TNF alpha will be analysed.
Autres noms:
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Autre: Patient with phenylketonuria
The intervention, specific to the study, is to take blood samples on patients with phenylketonuria
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Plasmatic cytokine and plasmatic CRP assay will be realised using luminex in both arms.
IL2, IL10,INF gamma, IL, IL6, ILB, TNF alpha will be analysed.
Autres noms:
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Que mesure l'étude ?
Principaux critères de jugement
Mesure des résultats |
Description de la mesure |
Délai |
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Plasma concentrations of pro-inflammatory cytokines
Délai: At the inclusion
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Plasmatic pro-inflammatory cytokine assay in PKU patients and healthy subjects.
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At the inclusion
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Plasma concentrations of CRP
Délai: At the inclusion
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Plasmatic CRP assay in PKU patients and healthy subjects.
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At the inclusion
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Mesures de résultats secondaires
Mesure des résultats |
Description de la mesure |
Délai |
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Plasma concentrations of phenylalanine
Délai: At the inclusion
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Plasmatic phenylalanine assay in PKU patients
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At the inclusion
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Plasma concentrations of tyrosine
Délai: At the inclusion
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Plasma tyrosine assay in PKU patients
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At the inclusion
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Collaborateurs et enquêteurs
Parrainer
Les enquêteurs
- Directeur d'études: François MAILLOT, MD-PhD, University Hospital, Tours
Publications et liens utiles
Publications générales
- van Spronsen FJ, van Wegberg AM, Ahring K, Belanger-Quintana A, Blau N, Bosch AM, Burlina A, Campistol J, Feillet F, Gizewska M, Huijbregts SC, Kearney S, Leuzzi V, Maillot F, Muntau AC, Trefz FK, van Rijn M, Walter JH, MacDonald A. Key European guidelines for the diagnosis and management of patients with phenylketonuria. Lancet Diabetes Endocrinol. 2017 Sep;5(9):743-756. doi: 10.1016/S2213-8587(16)30320-5. Epub 2017 Jan 10.
- Solverson P, Murali SG, Brinkman AS, Nelson DW, Clayton MK, Yen CL, Ney DM. Glycomacropeptide, a low-phenylalanine protein isolated from cheese whey, supports growth and attenuates metabolic stress in the murine model of phenylketonuria. Am J Physiol Endocrinol Metab. 2012 Apr 1;302(7):E885-95. doi: 10.1152/ajpendo.00647.2011. Epub 2012 Jan 31.
- Boulet L, Besson G, Van Noolen L, Faure P; ECOPHEN Study Group; Maillot F, Corne C. Tryptophan metabolism in phenylketonuria: A French adult cohort study. J Inherit Metab Dis. 2020 Sep;43(5):944-951. doi: 10.1002/jimd.12250. Epub 2020 Jun 4.
- Stroup BM, Nair N, Murali SG, Broniowska K, Rohr F, Levy HL, Ney DM. Metabolomic Markers of Essential Fatty Acids, Carnitine, and Cholesterol Metabolism in Adults and Adolescents with Phenylketonuria. J Nutr. 2018 Feb 1;148(2):194-201. doi: 10.1093/jn/nxx039.
- Matalon R, Surendran S, McDonald JD, Okorodudu AO, Tyring SK, Michals-Matalon K, Harris P. Abnormal expression of genes associated with development and inflammation in the heart of mouse maternal phenylketonuria offspring. Int J Immunopathol Pharmacol. 2005 Jul-Sep;18(3):557-65. doi: 10.1177/039463200501800316.
Dates d'enregistrement des études
Dates principales de l'étude
Début de l'étude (Réel)
Achèvement primaire (Réel)
Achèvement de l'étude (Réel)
Dates d'inscription aux études
Première soumission
Première soumission répondant aux critères de contrôle qualité
Première publication (Réel)
Mises à jour des dossiers d'étude
Dernière mise à jour publiée (Réel)
Dernière mise à jour soumise répondant aux critères de contrôle qualité
Dernière vérification
Plus d'information
Termes liés à cette étude
Termes MeSH pertinents supplémentaires
Autres numéros d'identification d'étude
- DR210098
- 2021-A01035-36 (Autre identifiant: IdRCB)
Informations sur les médicaments et les dispositifs, documents d'étude
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