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| ID | Type | Description | Link |
|---|---|---|---|
| 2021-A01035-36 | Other Identifier | IdRCB |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Healthy subject | Other | 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. |
|
| Patient with phenylketonuria | Other | The intervention, specific to the study, is to take blood samples on patients with phenylketonuria |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Blood samples | Biological | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| Plasma concentrations of pro-inflammatory cytokines | Plasmatic pro-inflammatory cytokine assay in PKU patients and healthy subjects. | At the inclusion |
| Plasma concentrations of CRP | Plasmatic CRP assay in PKU patients and healthy subjects. | At the inclusion |
| Measure | Description | Time Frame |
|---|---|---|
| Plasma concentrations of phenylalanine | Plasmatic phenylalanine assay in PKU patients | At the inclusion |
| Plasma concentrations of tyrosine | Plasma tyrosine assay in PKU patients |
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Inclusion Criteria (patient with PKU)
Inclusion Criteria (healthy volunteer)
Exclusion Criteria, common to healthy volunteer and patient with phenylketonuria
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| Name | Affiliation | Role |
|---|---|---|
| François MAILLOT, MD-PhD | University Hospital, Tours | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Clinical investigation center, University Hospital, Tours | Tours | 37044 | France | |||
| Internal Medicine Service, University Hospital, Tours |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 22297302 | Background | 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. | |
| 28082082 |
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| ID | Term |
|---|---|
| D010661 | Phenylketonurias |
| ID | Term |
|---|---|
| D020739 | Brain Diseases, Metabolic, Inborn |
| D001928 | Brain Diseases, Metabolic |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
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| ID | Term |
|---|---|
| D001800 | Blood Specimen Collection |
| ID | Term |
|---|---|
| D013048 | Specimen Handling |
| D019411 | Clinical Laboratory Techniques |
| D019937 | Diagnostic Techniques and Procedures |
| D003933 | Diagnosis |
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One group of healthy subject and one group of patient with phenylketonuria. Primary objective is to compare inflammation profile between the two groups through cytokine assay.
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|
| At the inclusion |
| Tours |
| 37044 |
| France |
| 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. |
| 32392388 | Background | 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. |
| 29490096 | Background | 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. |
| 16164837 | Background | 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. |
| 37927482 | Result | Giret C, Dos Santos Y, Blasco H, Paget C, Gonzalez L, Tressel N, Dieu M, Bigot A, Gissot V, Audemard-Verger A, Maillot F. No evidence for systemic low-grade inflammation in adult patients with early-treated phenylketonuria: The INGRAPH study. JIMD Rep. 2023 Oct 4;64(6):446-452. doi: 10.1002/jmd2.12366. eCollection 2023 Nov. |
| D009422 | Nervous System Diseases |
| D000592 | Amino Acid Metabolism, Inborn Errors |
| D008661 | Metabolism, Inborn Errors |
| D030342 | Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
| D011677 | Punctures |
| D013514 | Surgical Procedures, Operative |
| D008919 | Investigative Techniques |