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

NCT04879277 | Completed

• 2 other identifiers: DR2100982021-A01035-36
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 2

Brief 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.

Conditions

Phenylketonuria

Keywords

Low grade inflammation; Cardiovascular; Phenylketonuria

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (2)

• Plasma concentrations of phenylalanine

  At the inclusion

• Plasma concentrations of tyrosine

  At the inclusion

Study Arms (2)

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.

Biological: Blood samples

Patient with phenylketonuria

OTHER

The intervention, specific to the study, is to take blood samples on patients with phenylketonuria

Biological: Blood samples

Interventions

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.

Also known as: Plasmatic Cytokine and plasmatic CRP assay

Healthy subject; Patient with phenylketonuria

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age \>/= 18 years old
• Phenylketonuria diagnosis
• Fasting condition
• Registered with a social security system
• Patient consent
• 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

You may not qualify if:

• Pregnant and lactating women
• Subject to legal protection measures.
• Chronic or acute inflammatory disease
• Undergoing anti inflammatory treatment
• Surgery in the previous months
• Diabetes
• Included in other therapeutic trial

Sponsors & Collaborators

• University Hospital, Tours: lead

Study Sites (2)

Clinical investigation center, University Hospital, Tours

Tours, 37044, France

Location

Internal Medicine Service, University Hospital, Tours

Tours, 37044, France

Location

Related Publications (6)

• 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.

  PMID: 22297302 BACKGROUND

• 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.

  PMID: 28082082 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.

  PMID: 32392388 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.

  PMID: 29490096 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.

  PMID: 16164837 BACKGROUND

• 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.

  PMID: 37927482 RESULT

MeSH Terms

Conditions

Phenylketonurias

Interventions

Blood Specimen Collection

Condition Hierarchy (Ancestors)

Brain Diseases, Metabolic, Inborn; Brain Diseases, Metabolic; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Amino Acid Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• François MAILLOT, MD-PhD

  University Hospital, Tours

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: SCREENING
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: May 4, 2021
• First Posted: May 10, 2021
• Study Start: May 26, 2021
• Primary Completion: August 25, 2021
• Study Completion: August 25, 2021
• Last Updated: December 22, 2025

Record last verified: 2025-12

Locations

FR (2)