Study of Low-grade Systemic Inflammation in Adult Patients With Phenylketonuria

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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Etude de l'INflammation systémique de Bas GRade Chez Les Patients Adultes Atteints de PHénylcétonurie

Conditions
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Phenylketonuria

Intervention / Treatment
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* Biological: Blood samples


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Screening
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: 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.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Healthy subject<br>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. | Biological: Blood samples<br>* 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.<br>* Other names: Plasmatic Cytokine and plasmatic CRP assay;|
| Other: Patient with phenylketonuria<br>The intervention, specific to the study, is to take blood samples on patients with phenylketonuria | Biological: Blood samples<br>* 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.<br>* Other names: Plasmatic Cytokine and plasmatic CRP assay;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | 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 | 

Secondary Outcome Measures

| Outcome Measure | 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 | At the inclusion | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Low grade inflammation, Cardiovascular, Phenylketonuria