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

Phenylketonuria Clinical Trial

— INGRAPH  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04879277
• Other study ID #: DR210098
• Secondary ID: 2021-A01035-36
• Status: Completed
• Phase: N/A
• Start date: May 26, 2021
• Est. completion date: August 25, 2021

Study information

• Verified date: September 2021
• Source: University Hospital, Tours
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 40
• Est. completion date: August 25, 2021
• Est. primary completion date: August 25, 2021
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Phenylketonuria
• Phenylketonurias

Intervention

Biological:
• Blood samples
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.

Locations

Country	Name	City	State
France	Clinical investigation center, University Hospital, Tours	Tours
France	Internal Medicine Service, University Hospital, Tours	Tours

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital, Tours

Country where clinical trial is conducted

France, 

References & Publications (5)

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

van Spronsen FJ, van Wegberg AM, Ahring K, Bélanger-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. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Plasma concentrations of pro-inflammatory cytokines	Plasmatic pro-inflammatory cytokine assay in PKU patients and healthy subjects.	At the inclusion
Primary	Plasma concentrations of CRP	Plasmatic CRP assay in PKU patients and healthy subjects.	At the inclusion
Secondary	Plasma concentrations of phenylalanine	Plasmatic phenylalanine assay in PKU patients	At the inclusion
Secondary	Plasma concentrations of tyrosine	Plasma tyrosine assay in PKU patients	At the inclusion