Intellectual DisabilityNEXTOMIXNCT07755098
Integration of New Generation Multi-omics Analyses for the Diagnosis of Genetic Neurodevelomental Disorders
A study testing Re-analysis of available srGS data, Re-analysis of available srGS data, followed by complementary analyses (lrGS sequencing, mRNA, and GMOs) and srGS sequencing in people with Intellectual Disability and Neurodevelopmental Disorder (Diagnosis), run by Centre Hospitalier Universitaire Dijon at 1 site in France.
Trial summary
Neurodevelopmental disorders (NDDs), including intellectual disability (ID), represent the most common indication for genetic testing. Affecting up to 3% of the general population, NDDs are characterized by significant clinical and genetic heterogeneity. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Intellectual Disability, Neurodevelopmental Disorder (Diagnosis), srGS
- What is being tested?
- Re-analysis of available srGS data, Re-analysis of available srGS data, followed by complementary analyses (lrGS sequencing, mRNA, and GMOs) and srGS sequencing
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 132 participants
- Where
- 1 siteFrance
- Study dates
- Sep 2026to Mar 2029
- Phase
- Interventional
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 Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Index case (minor or adult) with severe to profound intellectual disability or syndromic neurodevelopmental disorder without an identified molecular diagnosis. - Index case with a negative srGS result.
- Sample collection possible from the index case (blood and skin biopsy) and their biological parent(s) (blood) if material is not otherwise available.
- Signed consent from the adult index case, or from the legal representatives or guardian (as applicable) of a minor index case, and from their parent(s).
Who cannot join
- - Index case or parent(s) not affiliated with or not covered by a social security scheme.
- Diagnostic hypothesis considered highly probable, for which an available targeted molecular test costs less than the proposed strategy.
- Suspicion of an acquired cause for the symptoms.
- Minor parent(s).
- Parent subject to a legal protection measure, or incapacitated or otherwise unable to provide informed consent.
- Pregnant, birthing, or breastfeeding woman.
- Participant (index case or parent) who has previously undergone allogeneic hematopoietic stem cell transplantation, rendering blood sample analysis uninformative.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
France1 site
Chu Dijon Bourgogne
Dijon, 21000
Louis ARNOULD, Pr, 03.80.29.34.53 ext. +33, Louis.arnould@chu-dijon.fr
About this study
Neurodevelopmental disorders (NDDs), including intellectual disability (ID), represent the most common indication for genetic testing. Affecting up to 3% of the general population, NDDs are characterized by significant clinical and genetic heterogeneity. Although short-read genome sequencing (srGS) has driven major advances through the France Genomic Medicine 2025 Plan (PFMG2025), a substantial proportion of patients still lack a molecular diagnosis.
These results are partly explained by the limitations of short-read genome sequencing (srGS). Although effective in many cases, this technology performs poorly in detecting complex structural rearrangements, anomalies within repetitive or GC-rich regions, epigenetic variations, and certain intronic variants. Furthermore, srGS does not allow for the direct assessment of the functional impact of genetic variations on splicing or gene expression. Following a negative srGS result, periodic reanalysis of sequencing data via the PFMG2025 laboratories (AURAGEN and SeqOIA) is the only diagnostic option currently available in routine practice. However, these reanalyses are constrained by financial and staffing limitations as well as strict eligibility criteria, making it difficult for many patients-particularly those with stable neurodevelopmental disorders (NDDs)-to obtain a diagnosis. Moreover, they often consist merely of a data review without bioinformatic updates, and the turnaround times-frequently exceeding one year-contribute to the diagnostic odyssey. Utilizing updated pipelines tailored to the specific characteristics of NDDs for the re-examination of srGS data could serve as an initial source of new diagnoses.
Read more
Complementary technologies-such as messenger RNA sequencing (mRNA-seq), optical genome mapping (OGM), and long-read genome sequencing (lrGS)-are available and offer solutions to overcome the limitations of short-read genome sequencing (srGS). In particular, they enable the identification of complex structural variants and the assessment of the functional impact of point variants. Despite their potential, their routine use remains limited due to cost and technical complexity.
Our study proposes a combined strategy to address the limitations of current approaches and improve the diagnosis of neurodevelopmental disorders (NDDs) that remain unresolved after short-read genome sequencing (srGS). It begins with a re-analysis of sequencing data using customized bioinformatics pipelines tailored to the patients' specific clinical profiles. In cases of inconclusive results, innovative multi-omics analyses (mRNA-seq, OGM, and long-read genome sequencing/lrGS) will be employed to investigate complex genetic variants. As multi-omics approaches are not currently integrated into the PFMG2025 framework, the project's findings will be crucial in demonstrating their added value for NDD diagnosis and could pave the way for their inclusion in a future PFMG. By anticipating these developments, NextOmix will help define the diagnostic strategies of the future, aligned with technological advancements and patient needs.
- Conditions
- Intellectual Disability, Neurodevelopmental Disorder (Diagnosis), srGS, lrGS, Short-read Genome Sequencing, Long-read Genome Sequencing
- Being tested
- Re-analysis of available srGS data, Re-analysis of available srGS data, followed by complementary analyses (lrGS sequencing, mRNA, and GMOs), srGS sequencing, Short-read sequencing (srGS) followed by long-read sequencing (lrGS,), mRNA-sequencing and GMO testing
- Medical subject headings
- Intellectual Disability, Neurodevelopmental Disorders, Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Re-analysis of available srGS dataDiagnostic test
Re-analysis of available srGS data without further analysis, as the results were positive for the causal diagnosis.
Re-analysis of available srGS data, followed by complementary analyses (lrGS sequencing, mRNA, and GMOs)Diagnostic test
Re-analysis of available srGS data followed by additional analyses (lrGS sequencing, mRNA-seq, and GMO testing), as the srGS data are negative for the causal diagnosis.
srGS sequencingDiagnostic test
New srGS sequencing without additional analyses, as it is positive for the causal diagnosis.
Short-read sequencing (srGS) followed by long-read sequencing (lrGS,), mRNA-sequencing and GMO testingDiagnostic test
New srGS sequencing followed by additional analyses (lrGS sequencing, mRNA-seq, and GMO testing) because the srGS data are negative for the causal diagnosis.
| Study group | Role | What they receive |
|---|---|---|
| Patient with severe to profound intellectual disability | Other | Not described Receives: Diagnostic Test: Re-analysis of available srGS data; Diagnostic Test: Re-analysis of available srGS data, followed by complementary analyses (lrGS sequencing, mRNA, and GMOs); Diagnostic Test: srGS sequencing; Diagnostic Test: Short-read sequencing (srGS) followed by long-read sequencing (lrGS,), mRNA-sequencing and GMO testing |
| Patient with a syndromic neurodevelopmental disorder with intellectual disability | Other | Not described Receives: Diagnostic Test: Re-analysis of available srGS data; Diagnostic Test: Re-analysis of available srGS data, followed by complementary analyses (lrGS sequencing, mRNA, and GMOs); Diagnostic Test: srGS sequencing; Diagnostic Test: Short-read sequencing (srGS) followed by long-read sequencing (lrGS,), mRNA-sequencing and GMO testing |
| Patient with a syndromic neurodevelopmental disorder without intellectual disability | Other | Not described Receives: Diagnostic Test: Re-analysis of available srGS data; Diagnostic Test: Re-analysis of available srGS data, followed by complementary analyses (lrGS sequencing, mRNA, and GMOs); Diagnostic Test: srGS sequencing; Diagnostic Test: Short-read sequencing (srGS) followed by long-read sequencing (lrGS,), mRNA-sequencing and GMO testing |
What is being measured
The primary outcome is the main question the study is designed to answer.
Identification of a causative diagnosis (class 4 or 5 variant according to American College of Medical Genetics criteria) explaining the phenotype and validated during a multidisciplinary team meeting.
Identification of a causative diagnosis (class 4 or 5 variant according to American College of Medical Genetics criteria) explaining the phenotype and validated during a multidisciplinary team meeting.
Measured: Between 4 and 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Aug 2026
- Study startSep 2026 (estimated)
- Primary completionMar 2029 (estimated)
- Study completionMar 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Intellectual DisabilityStudies of the same condition, open and under way.
- 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
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 132 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Centre Hospitalier Universitaire Dijon
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07755098
- Sponsor's protocol ID
- MAZEL PHRCI 2024
- Acronym
- NEXTOMIX
- Status last verified
- Aug 2026
- First submitted
- 5 Aug 2026
- Last updated
- 10 Aug 2026
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No