Molecular Autopsy in Young Individuals With Sudden Cardiac Death
ConditionTachycardia
Trial statusRecruiting
Trial phaseNot listed
Trial typeObservational
Biological sexAll
Age5-50
SponsorUniversity of Sao Paulo
About this trial
The goal of this observational study is to create and test a pilot workflow for molecular autopsy (genetic testing after death) in children and adults aged 1 to 50 years who died suddenly from an unexplained cause and were examined at the Death Verification Service of the city of São Paulo, Brazil.
The main questions it aims to answer are:
* How often can a genetic cause of sudden death be found in young people in Brazil? * Can first-degree relatives who carry the same genetic change be identified and referred for heart screening before they have symptoms?
Sudden cardiac death in young people is often caused by inherited heart diseases, such as heart rhythm disorders and diseases of the heart muscle. Death may be the first sign of the disease in a family. Most of what is known comes from studies in North America, Europe and Australia, and there are no such data for the Brazilian population.
After a family member gives consent, the researchers will:
* Interview the family using a verbal autopsy questionnaire and review the autopsy report and death certificate * Collect blood or tissue during the autopsy for genetic testing (whole exome sequencing) * Examine the heart under the microscope
When a genetic cause is found, the results will be given to the responsible family member, and first-degree relatives (parents, siblings and children) will be invited to take part. Relatives who agree will give a small blood sample (about 10 mL) to test for the same genetic change. Relatives who carry the change will be referred for heart screening.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Male or female, aged 1 to 50 years at the time of death
Unexplained sudden death, defined as an unexpected, non-traumatic death occurring within 1 hour of symptom onset in an apparently healthy individual or, if unwitnessed, within 24 hours of the individual last being seen alive and asymptomatic
Autopsy performed at the Death Verification Service of the City of São Paulo (SVOC-USP)
Informed consent provided by the legally responsible family member
Disqualifiers
First-degree relative (parent, sibling or child) of an index case in whom a pathogenic or likely pathogenic variant associated with inherited cardiac disease was identified
Informed consent provided by the participant or, when applicable, by a legal representative
Trial population
individuals aged 1 to 50 years with unexplained sudden death who undergo autopsy at the Death Verification Service of the City of São Paulo (SVOC-USP), São Paulo, Brazil. First-degree relatives: parents, siblings and children of index cases in whom a pathogenic or likely pathogenic variant associated with inherited cardiac disease is identified, evaluated at the Heart Institute (InCor), Hospital das Clínicas, University of São Paulo Medical School.
Trial design
Design model
Family-based
Time perspective
Prospective
Treatments tested in this trial
Molecular autopsy by whole exome sequencing
GeneticPost-mortem genetic testing of index cases using whole exome sequencing of DNA extracted from blood or tissue collected at autopsy, with variant classification according to ACMG criteria. Performed together with a verbal autopsy questionnaire, review of the autopsy report and death certificate, and histopathological analysis of the heart.
Cascade genetic screening by targeted Sanger sequencing
GeneticTargeted Sanger sequencing of the variant identified in the index case, using a peripheral blood sample (about 10 mL) from first-degree relatives. Carriers of pathogenic or likely pathogenic variants are referred for clinical cardiovascular screening.
Treatment groups
200 Participants
are divided into 1 treatment groupGroup A: Observation2 interventions
Trial outcomes
Primary outcomes
1
Diagnostic yield of molecular autopsy
Proportion of index cases in whom a pathogenic or likely pathogenic variant associated with inherited cardiac disease is identified by whole exome sequencing, classified according to ACMG criteria.
Time frame
From sample collection at autopsy to reporting of genetic results, assessed up to 3 yearsSecondary outcomes
1
Frequency of variants of uncertain significance
Proportion of index cases with at least one variant of uncertain significance in genes associated with inherited cardiac disease, according to ACMG criteria.
Time frame
From sample collection at autopsy to reporting of genetic results, assessed up to 3 years2
Distribution of genetic diagnoses by disease category
Number of index cases with pathogenic or likely pathogenic variants, by gene and disease category (primary arrhythmia syndromes, cardiomyopathies, or other inherited cardiac diseases).
Time frame
From sample collection at autopsy to reporting of genetic results, assessed up to 3 years3
Histopathological findings in the heart
Proportion of index cases with macroscopic or microscopic cardiac abnormalities (such as myocardial fibrosis, fatty infiltration, hypertrophy, coronary anomalies or ischemic injury) on pathological examination.
Time frame
From autopsy to completion of pathological analysis, assessed up to 3 years4
Carrier rate among first-degree relatives
Proportion of tested first-degree relatives who carry the pathogenic or likely pathogenic variant identified in the index case, assessed by targeted Sanger sequencing
Time frame
From the index case genetic report to relative testing, assessed up to 3 yearSponsors and contacts
Click on the lead sponsor to view all of their trials.
Source ClinicalTrials.gov