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PhenylketonuriaINGRAPHNCT04879277

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

A study testing Blood samples in people with Phenylketonuria, run by University Hospital, Tours at 2 sites in France.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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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. Read more about this study

Who is it for?
Ages 18 years and olderHealthy volunteers can take part
Conditions the study is for
Phenylketonuria
What is being tested?
Blood samples
Could I receive a placebo?
No, everyone receives an active treatment
How many people
40 participants
Where
2 sitesFrance
Study dates
26 May 2021to 25 Aug 2021
Phase
Interventional
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • Healthy volunteers accepted
  • Adult, Older adult

Who may be able to join

  • Age >/= 18 years old
  • Phenylketonuria diagnosis
  • Fasting condition
  • Registered with a social security system
  • Patient consent
  • Age >/= 18 years old
Show all 20Show fewer
  • 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

Who cannot join

None listed.

Trial locations and contacts

2 sites in 1 country.

France2 sites

  • Clinical investigation center, University Hospital, Tours

    Tours, 37044

  • Internal Medicine Service, University Hospital, Tours

    Tours, 37044

Other trials in France

About this study

Official title: 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.

Read the detailed 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.

Conditions
Phenylketonuria
Being tested
Blood samples
Keywords
Low grade inflammation, Cardiovascular, Phenylketonuria
Medical subject headings
Phenylketonurias

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Blood samplesBiological

    Also called Plasmatic Cytokine and plasmatic CRP assay

    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.

Study groups in NCT04879277
Study groupRoleWhat they receive
Healthy subjectOtherThe 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.
Receives: Biological: Blood samples
Patient with phenylketonuriaOtherThe intervention, specific to the study, is to take blood samples on patients with phenylketonuria
Receives: Biological: Blood samples

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Plasma concentrations of pro-inflammatory cytokines

    Plasmatic pro-inflammatory cytokine assay in PKU patients and healthy subjects.

    Measured: At the inclusion

  2. Plasma concentrations of CRP

    Plasmatic CRP assay in PKU patients and healthy subjects.

    Measured: At the inclusion

Secondary outcomes (2)

  1. Plasma concentrations of phenylalanine

    Plasmatic phenylalanine assay in PKU patients

    Measured: At the inclusion

  2. Plasma concentrations of tyrosine

    Plasma tyrosine assay in PKU patients

    Measured: At the inclusion

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted10 May 2021
  2. Study start26 May 2021
  3. Primary completion25 Aug 2021
  4. Study completion25 Aug 2021

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase N/A
Primary purpose
Screening
Allocation
Non-randomised
Intervention model
Parallel groups
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)
Enrolment
40 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04879277
Sponsor's protocol ID
DR210098
Other IDs
2021-A01035-36
Acronym
INGRAPH
Status last verified
Dec 2025
First submitted
4 May 2021
Last updated
22 Dec 2025
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No

Publications

  • 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.

    PubMed 22297302

  • 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.

    PubMed 28082082

  • 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.

    PubMed 32392388

  • 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.

    PubMed 29490096

  • 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.

    PubMed 16164837

  • 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.

    PubMed 37927482

Questions about this trial

What is this clinical trial studying?

A study testing Blood samples in people with Phenylketonuria, run by University Hospital, Tours at 2 sites in France.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 20 inclusion and 0 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 22 Dec 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in France. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Plasma concentrations of pro-inflammatory cytokines (time frame: At the inclusion). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04879277, which also lists 6 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Dec 2025.

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