Phenylketonuria (PKU)GENOPHENNCT07484945
Multiomics Approach in Adult Patients With Phenylketonuria
An observational study of Phenylketonuria (PKU), run by University Hospital, Tours at 15 sites in France.
Trial summary
The GENOPHEN study aims to explore the links between the genome, metabolomic profile, and clinical phenotype in adults with early-treated PKU. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Phenylketonuria (PKU)
- How many people
- 149 participants
- Where
- 15 sitesFrance
- Study dates
- 23 Mar 2026to Mar 2028
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
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
- No healthy volunteers
- Adult, Older adult
Study population: PKU adult patients
Who may be able to join
- 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)
Who cannot join
- 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.
Trial locations and contacts
15 sites in 1 country. Contact the study team or a site near you to ask about taking part.
15 sites in 1 country
France15 sites, 15 recruiting
- Not yet recruiting
University hospital
Angers, 49000
Christian LAVIGNE, Pr, 241357700 ext. +33, ChLavigne@chu-angers.fr
- Not yet recruiting
University hospital
Bordeaux, 33000
Vincent RIGALLEAU, Pr, 556555078 ext. +33, vincent.rigalleau@chu-bordeaux.fr
- Not yet recruiting
University hospital
Brest, 29000
Elise SACAZE, Dr, SACAZE Elise <elise.sacaze@chu-brest.fr>
- Not yet recruiting
University hospital
Dijon, 21000
Vanessa LEGUY-SEGUIN, Dr, 380293432 ext. +33, vanessa.leguy-seguin@chu-dijon.fr
- Not yet recruiting
University hospital
Grenoble, 38000
Gérard BESSON, Dr, gerard.besson@univ-grenoble-alpes.fr
- Not yet recruiting
University hospital
Lille, 59000
Claire DOUILLARD, Dr, 3 20 44 45 44 ext. +33, Claire.DOUILLARD@chu-lille.fr
- Not yet recruiting
Civil Hospitals
Lyon, 69000
Sybil CHARRIERE, Pr, 4 72 68 13 31 ext. +33, sybil.charriere@chu-lyon.fr
- Not yet recruiting
Conception hospital
Marseille, 13000
Karin MAZODIER, Dr, 4 91 38 23 79 ext. +33, Karin.MAZODIER@ap-hm.fr
- Not yet recruiting
University hospital
Nancy, 54000
François FEILLET, Pr, 383154796 ext. +33, f.feillet@chru-nancy.fr
- Not yet recruiting
University hospital
Nantes, 44000
Alice KUSTER, Dr, 240083483 ext. +33, alice.kuster@chu-nantes.fr
- Not yet recruiting
Necker hospital
Paris, 75000
Jean-Baptiste ARNOUX, Dr, 1.44.49.40.23 ext. +33, jean-baptiste.arnoux@aphp.fr
- Not yet recruiting
University hospital
Rennes, 35000
Paul ROLLIER, Dr, 2 99 26 67 44 ext. +33, Paul.ROLLIER@chu-rennes.fr
- Not yet recruiting
University hospital
Saint-Etienne, 42000
Anne-Cécile CHAUX, Dr, a.cecile.chaux@chu-st-etienne.fr
- Not yet recruiting
University hospital
Toulouse, 31000
Julien MAQUET, Dr, 5 61 77 96 78 ext. +33, maquet.j@chu-toulouse.fr
- Recruiting
university hospital, Tours
Tours, 37044
François MAILLOT, Pr, 2.47.47.37.15 ext. +33, francois.maillot@univ-tours.fr
About this study
Official title: 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.
Read the 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.
- Conditions
- Phenylketonuria (PKU)
- Keywords
- saliva, genetics
- Medical subject headings
- Phenylketonurias
What is being measured
The primary outcome is the main question the study is designed to answer.
Identification of metabolite clusters
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.)
Measured: Enrolment
Identification of genetic variants DNAJC12, HULC, SLC7A5, and SHANK and other ones
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.
Measured: Enrolment
Secondary outcomes (7)
Number of patients with neurological complications
Measured: Enrolment
average intelligence quotient (IQ)
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)
Measured: Enrolment
California Verbal Learning Test
CVLT results identified in the ECOPHEN cohort study. There is no minimum or maximum score; it is a "raw" score.
Measured: Enrolment
Trail Making Test
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.
Measured: Enrolment
Beck Depression Inventory
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
Measured: Enrolment
Weight changes
Body mass index (Kg/m2)
Measured: Time of enrollment
Bone mineral density changes
Bone mineral density, measured by DWA, expressed as Z-scores
Measured: Enrolment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Mar 2026
- Study start23 Mar 2026
- Primary completionMar 2028 (estimated)
- Study completionMar 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Phenylketonuria (PKU)Studies of the same condition, open and under way.
- More trials run by University Hospital, ToursThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case only
- Time perspective
- Prospective
- Enrolment
- 149 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University Hospital, Tours
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Yannick MOUPATAM-NGAMBY-ADRIAASEN, Sir, Principal investigator, University, Tours
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07484945
- Sponsor's protocol ID
- DR250249 - GENOPHEN
- Acronym
- GENOPHEN
- Status last verified
- Apr 2026
- First submitted
- 12 Feb 2026
- Last updated
- 6 May 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 6 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Relationships Between the Genome and Metabolomic and Phenomic Signatures in Adult Patients With Early-Treated Phenylketonuria: a Multicenter Cross-sectional Study
- ClinicalTrials.gov ID
- NCT07484945
- Acronym / sponsor ID
- GENOPHEN / DR250249 - GENOPHEN
- Conditions
- Phenylketonuria (PKU)
- Keywords
- saliva, genetics
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 149 participants (estimated)
- Lead sponsor
- University Hospital, ToursUniversity, hospital or other
- Study start
- 23 Mar 2026 (actual)
- Primary completion
- Mar 2028 (estimated)
- Study completion
- Mar 2028 (estimated)
- First posted
- 20 Mar 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The GENOPHEN study aims to explore the links between the genome, metabolomic profile, and clinical phenotype in adults with early-treated PKU.
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 design
- Observational model
- Case only
- Time perspective
- Prospective
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- PKU adult patients
Key inclusion criteria (5 listed)
- 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)
Key exclusion criteria (3 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
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.)
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.
7 secondary outcomes
Number of patients with neurological complications
Time frame: Enrolment
average intelligence quotient (IQ)
Time frame: Enrolment
California Verbal Learning Test
Time frame: Enrolment
Trail Making Test
Time frame: Enrolment
Beck Depression Inventory
Time frame: Enrolment
Weight changes
Time frame: Time of enrollment
Bone mineral density changes
Time frame: Enrolment
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 May 2026.
- Individual participant dataSharing planned: Undecided
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RecruitingPhase 2
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RecruitingPhase 3
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Impact of Phenylalanine Elevations on Brain and Cognition in Adult PKU Carriers
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RecruitingPhase 3
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Yannick MOUPATAM-NGAMBY-ADRIAASEN, Sir principal investigator
University, Tours
15 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Phenylketonuria (PKU), run by University Hospital, Tours at 15 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 5 inclusion and 3 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: looking for participants now, as of the sponsor's last update on 6 May 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 15 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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact François MAILLOT, Pr (2.47.47.37.15 ext. +33, francois.maillot@univ-tours.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Identification of metabolite clusters (time frame: Enrolment). 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?
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 6 May 2026.