EpiSign International: Expanding Epigenomic Testing in Rare Disease
Trial statusNot yet recruiting
Trial phaseNot listed
Trial typeObservational
Biological sexAll
AgeNot listed
SponsorUniversity of Manchester
About this trial
The purpose of this study is to assess the utility of EpiSign software and an integrated DNA methylation and copy number variant (CNV) microarray technology in helping to diagnose individuals with rare diseases. EpiSign is a proprietary technology developed by EpiSign Inc. that uses DNA methylation patterns as biomarkers for rare diseases, including genetic disorders and conditions associated with environmental exposures. DNA methylation microarrays measure DNA methylation levels at specific locations across the genome. CNV microarray technology uses a similar approach to identify gains or losses of DNA. CNV microarray analysis is an established methodology used in the diagnosis of rare diseases.
The first phase of the study will assess the utility of EpiSign analysis using standard EPIC DNA methylation microarrays as part of the diagnostic assessment of individuals with suspected rare diseases. The second phase will assess the utility of EpiSign analysis using newly developed integrated EPIC/CNV microarrays and evaluate the technical performance of these microarrays in detecting CNVs, as part of the diagnostic assessment of individuals with suspected rare diseases.
Patients with suspected rare diseases will be recruited from Manchester University NHS Foundation Trust. Participants will provide a blood sample, which will be used to analyse their DNA methylation profile and detect CNVs. The study is expected to last approximately 24 months from study initiation.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Eligible for, or have undergone, standard-of-care first-tier genetic testing at the participating site with a negative or inconclusive result.
No established molecular or clinical diagnosis explaining their presentation.
No diagnostic result from subsequent/reflex genetic testing available at enrolment.
For Phase 2 CNV-positive participants: have undergone standard-of-care CNV testing at the participating site and have a CNV reported by standard-of-care testing.
Disqualifiers
Do not meet the applicable inclusion criteria.
Isolated, non-syndromic autism or isolated learning disability without additional features suggestive of a syndromic rare disorder.
Trial population
Individuals with suspected rare diseases undergoing diagnostic assessment at Manchester University NHS Foundation Trust. The study population includes patients who have no established molecular or clinical diagnosis explaining their presentation and who have either negative or inconclusive results from standard-of-care genetic testing or a reported copy number variant (CNV) requiring further assessment. Participants will be recruited into two study phases: Phase 1 includes individuals undergoing first-tier EpiSign assessment using a standard DNA methylation microarray, while Phase 2 includes individuals undergoing EpiSign assessment using an integrated DNA methylation/CNV microarray.
Trial design
Design model
Cohort
Time perspective
Prospective
Treatments tested in this trial
Integrated EPIC/CNV microarray with EpiSign analysis
Diagnostic testParticipants will undergo analysis using a newly developed integrated EPIC/CNV microarray capable of measuring genome-wide DNA methylation and detecting copy number variations from a single array. DNA methylation data will be analysed using EpiSign software to identify disease-associated episignatures. CNV data will be analysed to assess the technical performance and analytical yield of the integrated microarray for CNV detection. The study will also assess the potential utility of combining DNA methylation and CNV analysis within a single diagnostic assay.
EpiSign analysis with EPIC DNA methylation microarray
Diagnostic testParticipants will undergo genome-wide DNA methylation analysis using the standard Illumina EPIC DNA methylation microarray. The resulting DNA methylation data will be analysed using EpiSign software to identify disease-associated DNA methylation episignatures. EpiSign results will be assessed alongside clinical and genetic information to determine the additional diagnostic yield and clinical utility of EpiSign analysis in patients with suspected rare disease.
Treatment groups
192 Participants
are divided into 2 treatment groupsGroup A: Phase 1: EpiSign with EPIC DNA Methylation Array1 intervention
Group B: Phase 2: Integrated EPIC/CNV Array and EpiSign1 intervention
Trial outcomes
Primary outcomes
1
Additional diagnostic yield of EpiSign analysis
Proportion (%) of participants for whom EpiSign identifies a relevant episignature that contributes to a molecular or clinical diagnosis.
Time frame
Following completion of relevant genetic and EpiSign testing and collection of clinical data, expected approximately 12-18 months after study initiation.Secondary outcomes
1
Change in clinical management following EpiSign analysis
Proportion (%) of participants with a change in clinical management.
Time frame
Following completion of relevant genetic and EpiSign testing and collection of clinical data, expected approximately 12-18 months after study initiation.2
Change in diagnostic pathway following EpiSign analysis
Proportion (%) of participants with a change in diagnostic pathway.
Time frame
Following completion of relevant genetic and EpiSign testing and collection of clinical data, expected approximately 12-18 months after study initiation.3
Time to diagnosis following EpiSign analysis
Time in months.
Time frame
Following completion of relevant genetic and EpiSign testing and collection of clinical data, expected approximately 12-18 months after study initiation.4
Additional diagnostic investigations prompted by EpiSign analysis
Number of additional investigations per participant.
Time frame
Following completion of relevant genetic and EpiSign testing and collection of clinical data, expected approximately 12-18 months after study initiation.Sponsors and contacts
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Source ClinicalTrials.gov
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