Ignite Creation Date:
2026-03-26 @ 3:15 PM
Ignite Modification Date:
2026-03-30 @ 3:04 AM
Study NCT ID:
NCT07370792
Status:
RECRUITING
Last Update Posted:
2026-01-27
First Post:
2025-12-09
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Contribution of Optical Genome Mapping (OGM) in the Diagnosis of Multiple Congenital Malformations With or Without Intellectual Disability Without Genetic Abnormality
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2026-03-25'}, 'conditionBrowseModule': {'meshes': [{'id': 'D000013', 'term': 'Congenital Abnormalities'}, {'id': 'D000015', 'term': 'Abnormalities, Multiple'}], 'ancestors': [{'id': 'D009358', 'term': 'Congenital, Hereditary, and Neonatal Diseases and Abnormalities'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'D001800', 'term': 'Blood Specimen Collection'}], 'ancestors': [{'id': 'D013048', 'term': 'Specimen Handling'}, {'id': 'D019411', 'term': 'Clinical Laboratory Techniques'}, {'id': 'D019937', 'term': 'Diagnostic Techniques and Procedures'}, {'id': 'D003933', 'term': 'Diagnosis'}, {'id': 'D011677', 'term': 'Punctures'}, {'id': 'D013514', 'term': 'Surgical Procedures, Operative'}, {'id': 'D008919', 'term': 'Investigative Techniques'}]}}, 'protocolSection': {'designModule': {'phases': ['NA'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'NA', 'maskingInfo': {'masking': 'NONE', 'maskingDescription': 'Each sample will be pseudonymized as follows:\n\nCARTOGEN\\_N\\[patient number\\]-\\[initial of last name\\]-\\[initial of first name\\] Example: Pierre MARTIN, 15th enrolled patient → CARTOGEN\\_N\\[15\\]-\\[M\\]-\\[P\\]'}, 'primaryPurpose': 'DIAGNOSTIC', 'interventionModel': 'SINGLE_GROUP'}, 'enrollmentInfo': {'type': 'ESTIMATED', 'count': 55}}, 'statusModule': {'overallStatus': 'RECRUITING', 'startDateStruct': {'date': '2025-11-18', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2026-01', 'completionDateStruct': {'date': '2028-11-01', 'type': 'ESTIMATED'}, 'lastUpdateSubmitDate': '2026-01-20', 'studyFirstSubmitDate': '2025-12-09', 'studyFirstSubmitQcDate': '2026-01-20', 'lastUpdatePostDateStruct': {'date': '2026-01-27', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2026-01-27', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2028-11-01', 'type': 'ESTIMATED'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'diagnostic yield of optical genome mapping (OGM) in multiple congenital anomalies with or without intellectual disability when whole-genome sequencing (WGS) is non-contributive', 'timeFrame': 'day 1 (inclusion and blood collection)', 'description': 'Assessing the diagnostic yield of optical genome mapping (OGM) in multiple congenital anomalies with or without intellectual disability when whole-genome sequencing (WGS) is non-contributive (absence of causal genetic variation or detection of a variant of uncertain significance (VUS) or a single variant in a recessive disorder).'}], 'secondaryOutcomes': [{'measure': 'Number of reclassified variants intially considered as VUS (Variants of Uncertain/Unknown Signification)', 'timeFrame': 'day 1 (inclusion and blood collection)', 'description': 'Assessment of the number of variants initially classified as VUS (variants of uncertain/unknown significance) that were reclassified as benign or pathogenic variants'}, {'measure': 'Number of patients in whom a new candidate gene/pathogenic mechanism is identified', 'timeFrame': 'day 1 (inclusion and blood collection)'}, {'measure': 'Evaluation of the feasibility (duration) of the technique in current practice in 1st-line, 2nd-line (after routine tests such as chromosomal microarray, exome sequencing…), or 3rd-line in the case of non-contributive WGS based on several criteria', 'timeFrame': 'day 1 (inclusion and blood collection)', 'description': 'Evaluation of technical duration (hours)'}, {'measure': 'Evaluation of the feasibility of the technique (failure) in current practice in 1st-line, 2nd-line (after routine tests such as chromosomal microarray, exome sequencing…), or 3rd-line in the case of non-contributive WGS based on several criteria', 'timeFrame': 'day 1 (inclusion and blood collection)', 'description': 'failure rate number'}, {'measure': 'Evaluation of the feasibility of the technique (reprocessing) in current practice in 1st-line, 2nd-line (after routine tests such as chromosomal microarray, exome sequencing…), or 3rd-line in the case of non-contributive WGS based on several criteria', 'timeFrame': 'day 1 (inclusion and blood collection)', 'description': 'reprocessing rate number'}, {'measure': 'Evaluation of the feasibility of the technique (interpretation) in current practice in 1st-line, 2nd-line (after routine tests such as chromosomal microarray, exome sequencing…), or 3rd-line in the case of non-contributive WGS based on several criteria', 'timeFrame': 'day 1 (inclusion and blood collection)', 'description': 'Evaluation of biological interpretation time (hours)'}, {'measure': 'Assess the impact of using these new technologies on patient management.', 'timeFrame': 'day 1 (inclusion and blood collection)', 'description': 'Percentage of patients for whom the OGM results led to a change in clinical management.'}]}, 'oversightModule': {'oversightHasDmc': False, 'isFdaRegulatedDrug': False, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'keywords': ['multiple congenital anomalies', 'non-contributive whole-genome sequencing', 'optical genome mapping', 'structural variants', 'genetic diagnosis'], 'conditions': ['Congenital Malformations']}, 'descriptionModule': {'briefSummary': 'Congenital malformations result from an embryonic or foetal developmental disorder (DD) affecting one or more systems (cardiac, skeletal, nervous, etc.). These are referred to as multiple congenital anomalies (MCAs). They may be associated with an intellectual disability (ID)1.\n\nChromosomal analysis on Chromosomal Microarray Analysis (CMA) and gene panels or exome sequencing are the respective gold standard methods for chromosomal and molecular diagnosis of DD respectively2. In cases where no diagnosis is established after these first-line tests, short-read whole genome sequencing (WGS), via the Plan France Medicine Genomic 2020-2025 (AURAGEN), may be considered. This approach allows for diagnosis in nearly 40% of patients with DD3,4. However, many patients remain in diagnostic deadlock, likely due to the technical limitations of these methods, which potentially be overcome by emerging methodologies such as optical genome mapping (OGM)5,6,7,8,9. The investigators propose to systematically perform OGM in 30 patients presenting with MCA+/-ID who have inconclusive WGS result10.\n\nThe main objective is to assess the contribution of OGM in identifying structural variants not detected or poorly characterised by WGS in this clinical context. This work will also contribute to the ongoing of OGM in routine diagnostics and determine its role in the overall genetic diagnosis of MCA+/-ID. Additionally it may lead to the identification of new candidate genes and/or mechanisms of pathogenicity. If the results are promising, further clinical could expand this preliminary work into a larger-scale project. Improving the genetic diagnosis of DD should enhance the medical management of patients, currently in diagnostic deadlock, and their families.', 'detailedDescription': "Study Workflow\n\nPre-analytical Phase\n\nParticipation in the study will be offered to all patients meeting the inclusion and non-inclusion criteria by an investigator from the Department of Genetics, during a medical consultation in which the non-contributive whole-genome sequencing (WGS) result will have been communicated (Figure 1). Information regarding the study procedures and objectives will be provided at that time. The information sheet and consent form will be given to the patient (if an adult) or to the holders of parental authority (if the patient is a minor). After obtaining consent for both the genetic investigations and participation in the research project, the patient may be enrolled in the study. Blood samples required for the study will be collected, transferred to the laboratory, and secured for analysis according to the following protocol:\n\nPatient \\> 20 kg:\n\n2 × 5 mL EDTA blood tubes\n\n1. × 5 mL heparinized blood tube\n\n Patient 12-20 kg:\n2. × 5 mL EDTA blood tubes\n\nPatient 5-12 kg:\n\n1 × 5 mL EDTA blood tube\n\nSamples will be sent to the Cytogenetics Department, where they will be pseudonymized and secured. At least three aliquots of 1.5 mL EDTA blood and the remaining volume will be frozen at -80 °C for DNA extraction and long-fragment DNA extraction. A cell culture (peripheral blood lymphocytes) will also be performed to obtain a fixed chromosomal pellet from the heparinized tube, when available. If the heparinized sample is not available and the results of optical genome mapping require confirmation of a chromosomal abnormality by karyotype or FISH (i.e., contributive result), a second blood draw will be proposed during the clinical results-return consultation.\n\nAnalysis Frozen samples from the Cytogenetics Department of Clermont-Ferrand University Hospital (one per patient) will be transferred via TSE to the Department of Genetics at Reims University Hospital, designated to perform optical genome mapping while awaiting installation of the Saphyr scanner at Clermont-Ferrand University Hospital (DAN 2025 application).\n\nExtraction, labeling, and imaging of long DNA molecules will be performed using the manufacturer's kits, following the provided instructions.\n\nResults and Interpretation\n\nRaw data will be analyzed and validated by cytogeneticists at Reims University Hospital using Bionano Access and Solve® software. Data will also be securely shared with the project lead, responsible for:\n\nPerforming a second independent analysis (with Bionano Access and Solve, available in the Cytogenetics Department), leveraging expertise acquired through participation in previous projects.\n\nProviding final interpretation of results and disseminating clinically relevant findings for patient management.\n\nEach sample will therefore benefit from dual review and dual expertise, ensuring the reliability of the results.\n\nParental segregation studies may be proposed to facilitate biological interpretation. If needed, collection of parental samples and consent procedures will be coordinated by the Department of Medical Genetics at Clermont-Ferrand University Hospital. Conclusive results will be communicated to the clinician who prescribed the WGS for patient management and genetic counselling."}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['CHILD', 'ADULT', 'OLDER_ADULT'], 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria\n\n* Patients presenting with at least two congenital anomalies, with or without intellectual disability, and weighing more than 5 kg.\n* Whole-genome sequencing performed by the AURAGEN laboratory deemed non-contributive (absence of class 4 or 5 variants, or identification of a VUS, or identification of only one variant in the context of a recessive disorder).\n* Patient covered by a social security scheme.\n* Patient able to understand and to oppose participation in the study.\n* Written informed consent for genetic analyses, signed either by the patient or by their legal representatives (for minors), after clear and fair information about the study has been provided.\n\nNon-Inclusion Criteria\n\n* Patients for whom a non-genetic cause (infectious, environmental, or toxic) has been previously identified.\n* Inability to obtain a compliant sample.\n* Patient or holder of parental authority under guardianship or legal protection, deprived of liberty, or placed under court-ordered protection.'}, 'identificationModule': {'nctId': 'NCT07370792', 'acronym': 'CARTOGEN-N', 'briefTitle': 'Contribution of Optical Genome Mapping (OGM) in the Diagnosis of Multiple Congenital Malformations With or Without Intellectual Disability Without Genetic Abnormality', 'organization': {'class': 'OTHER', 'fullName': 'University Hospital, Clermont-Ferrand'}, 'officialTitle': 'CARTOGEN-N_Contribution of Optical Genome Mapping (OGM) in the Diagnosis of Multiple Congenital Malformations With or Without Intellectual Disability Without Genetic Abnormality Detected by Whole Genome Sequencing', 'orgStudyIdInfo': {'id': 'AOI 2024 PEBREL-RICHARD'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'single arm of patients with congenital malformations', 'interventionNames': ['Genetic: blood sample']}], 'interventions': [{'name': 'blood sample', 'type': 'GENETIC', 'description': "A blood sample will be collected after obtaining consent from the patient and/or their legal guardians. The number of tubes required (1 to 3) will be determined according to the patient's weight, for the purpose of performing optical genome mapping and any necessary confirmatory analyses in the event that a structural variant is identified.", 'armGroupLabels': ['single arm of patients with congenital malformations']}]}, 'contactsLocationsModule': {'locations': [{'city': 'Clermont-Ferrand', 'status': 'RECRUITING', 'country': 'France', 'contacts': [{'name': 'Lise Laclautre', 'role': 'CONTACT', 'email': 'promo_interne_drci@chu-clermontferrand.fr', 'phone': '+33473754963'}, {'name': 'Céline PEBREL-RICHARD', 'role': 'PRINCIPAL_INVESTIGATOR'}], 'facility': 'CHU clermont-Ferrand', 'geoPoint': {'lat': 45.77969, 'lon': 3.08682}}], 'centralContacts': [{'name': 'Lise Laclautre', 'role': 'CONTACT', 'email': 'promo_interne_drci@chu-clermontferrand.fr', 'phone': '+33473754963'}], 'overallOfficials': [{'name': 'Lise LACLAUTRE', 'role': 'STUDY_CHAIR', 'affiliation': 'University Hospital, Clermont-Ferrand'}]}, 'ipdSharingStatementModule': {'ipdSharing': 'NO'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Céline PEBREL-RICHARD', 'class': 'OTHER'}, 'responsibleParty': {'type': 'SPONSOR_INVESTIGATOR', 'investigatorTitle': 'Dr', 'investigatorFullName': 'Céline PEBREL-RICHARD', 'investigatorAffiliation': 'University Hospital, Clermont-Ferrand'}}}}