Multiomics Approach in Adult Patients With Phenylketonuria (GENOPHEN)

April 29, 2026 updated by: University Hospital, Tours

Relationships Between the Genome and Metabolomic and Phenomic Signatures in Adult Patients With Early-Treated Phenylketonuria: a Multicenter Cross-sectional Study

The GENOPHEN study aims to explore the links between the genome, metabolomic profile, and clinical phenotype in adults with early-treated PKU.

Study Overview

Status

Recruiting

Conditions

Detailed Description

• There is a wide clinical variability among PKU patients. Even siblings can present discrepancies regarding the phenotype. The reasons for that are not completely known. There are over 3,300 variants of the PAH gene, some of which influence the severity of the disease, but their impact in adulthood remains poorly understood. Other genes (SLC7A5, HULC, DNAJC12, SHANK family) could also modulate the phenotype.

Working Hypotheses:

  • Some genetic variants influence the severity of neuropsychological and systemic disorders in adults with early-treated PKU.
  • Metabolomic analysis of sera will identify new biomarkers correlated with the severity of the disease.

Methodology:

  • The study is based on the ECOPHEN cohort (187 adult PKU patients followed for 5 years), of which 150 will provide a DNA sample from saliva for whole-genome sequencing.
  • Genetic variants will be sought and correlated with clinical, biological, and neuropsychological data.
  • A non-targeted metabolomic analysis by LC-MS/MS will be performed on the sera, then the metabolic profiles will be associated with phenotypes and genotypes.

Objectives and Expected Outcomes:

  • Better understand the heterogeneity of the disease in adulthood.
  • Identify associations between genetic variants, metabolic profiles, and clinical evolution.
  • Pave the way for personalized management and new therapeutic approaches for adult PKU patients.

Study Type

Observational

Enrollment (Estimated)

149

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • France
      • Angers, France, 49000
        • Not yet recruiting
        • University Hospital
        • Contact:
      • Bordeaux, France, 33000
      • Brest, France, 29000
      • Dijon, France, 21000
      • Grenoble, France, 38000
      • Lille, France, 59000
      • Lyon, France, 69000
      • Marseille, France, 13000
        • Not yet recruiting
        • Conception hospital
        • Contact:
      • Nancy, France, 54000
        • Not yet recruiting
        • University Hospital
        • Contact:
      • Nantes, France, 44000
      • Paris, France, 75000
      • Rennes, France, 35000
        • Not yet recruiting
        • University Hospital
        • Contact:
      • Saint-Etienne, France, 42000
      • Toulouse, France, 31000
        • Not yet recruiting
        • University Hospital
        • Contact:
      • Tours, France, 37044

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Sampling Method

Non-Probability Sample

Study Population

PKU adult patients

Description

Inclusion Criteria:

  • PKU patients over the age of 18,
  • diagnosed through the newborn screening program,
  • patients who participated in the final visit of the ECOPHEN study,
  • affiliation with a health insurance plan,
  • informed consent dated and signed by patients for DNA analysis (saliva sample)

Exclusion Criteria:

  • Patients whose PKU diagnosis was not detected during neonatal screening,
  • Patients who have not signed a dated informed consent form,
  • Patients who are unable to provide a saliva sample.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Identification of metabolite clusters
Time Frame: Enrolment
untargeted metabolomic analysis of plasma samples collected during the ECOPHEN study Phenylalanine level (> 900 µmol/L, 900-600 µmol/L, < 600 µmol/L), response to BH4 (Complete response: decrease in Phe levels after treatment leading to normalization of Phe levels; partial response: 30% decrease without normalization; non-responder: decrease of less than 30% in Phe levels.)
Enrolment
Identification of genetic variants DNAJC12, HULC, SLC7A5, and SHANK and other ones
Time Frame: Enrolment

genome sequencing of DNA collected from saliva samples during the GENOPHEN study.

The DNAJC12, HULC, SLC7A5, and SHANK (SHANK1, SHANK2, and SHANK3) variants will be listed and classified as frequent (allele frequency > 1%) or rare (allele frequency < 1%) according to the gnomAD database. The same will apply to other variants potentially identified by genome sequencing.
Enrolment

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
average intelligence quotient (IQ)
Time Frame: Enrolment
WAIS IV results identified in the ECOPHEN cohort study (>= 130 : Very superior; 120-129 Superior; 110-119 High average; 90-109 Average; 80-89 : Low average; 70-79 Borderline; =< 69 Extremely low)
Enrolment
California Verbal Learning Test
Time Frame: Enrolment
CVLT results identified in the ECOPHEN cohort study. There is no minimum or maximum score; it is a "raw" score.
Enrolment
Trail Making Test
Time Frame: Enrolment
TMT results identified in the ECOPHEN cohort study. This is the number of seconds it takes to finish connecting the points on a "path" consisting of 25 points; the lower the number, the better (the patient is faster), but there isn't really a minimum and no maximum.
Enrolment
Beck Depression Inventory
Time Frame: Enrolment
BDI test results identified in the ECOPHEN cohort study The score ranges from 0 to 63, with the following qualitative interpretations: 0-13: minimal depression; 14-19: mild depression; 20-28: moderate depression; 29-63: severe depression
Enrolment
Weight changes
Time Frame: Time of enrollment
Body mass index (Kg/m2)
Time of enrollment
Bone mineral density changes
Time Frame: Enrolment
Bone mineral density, measured by DWA, expressed as Z-scores
Enrolment
Number of patients with neurological complications
Time Frame: Enrolment
Enrolment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University Hospital, Tours

Investigators

  • Principal Investigator: Yannick MOUPATAM-NGAMBY-ADRIAASEN, Sir, University, Tours

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 23, 2026

Primary Completion (Estimated)

March 1, 2028

Study Completion (Estimated)

March 1, 2028

Study Registration Dates

First Submitted

February 12, 2026

First Submitted That Met QC Criteria

March 17, 2026

First Posted (Actual)

March 20, 2026

Study Record Updates

Last Update Posted (Actual)

May 6, 2026

Last Update Submitted That Met QC Criteria

April 29, 2026

Last Verified

April 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • DR250249 - GENOPHEN

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Phenylketonuria (PKU)

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Israel

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe