Clinical trial NCT05158738: Inherited Cardiac cONditions In Kids
Official title: Inherited Cardiac cONditions In Kids: Understanding the Genetics and Outcomes of Paediatric Inherited CardiacConditions
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Inherited Cardiac Conditions
Cardiovascular Diseases
Lead sponsor: Imperial College London
Sponsor class: OTHER
Collaborators: name: Royal Brompton & Harefield NHS Foundation Trust
name: Great Ormond Street Hospital for Children NHS Foundation Trust
First posted: 2021-12-15
Enrollment: 300
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_ONLY
Time perspective: OTHER
Sampling method: NON_PROBABILITY_SAMPLE
Study population: * Males or females with a confirmed diagnosis of childhood onset (\<16 years) PCM and their parents.
* Males or females with childhood onset (\<16 years) of a rare inherited cardiac condition likely to be a monogenic condition and their parents.

Brief summary: All patients with heart disease should have the opportunity to participate in research into their condition, to advance knowledge and treatment. The investigators have built an online registry and database - The Heart Hive - to connect research-willing participants (with heart muscle disease) with active researchers and projects. Participants enrol and upload their own data through the website.This study uses The Heart Hive platform to study cardiomyopathies - heart muscle disease. These are progressive diseases, and there is a need to better understand what factors affect the chances of developing cardiomyopathy, and how the condition progresses. The study will collect information about participants diagnosis, DNA for genetic analysis, and then follow participants' clinical progress. The study will identify genetic variants that cause cardiomyopathy, and determine which specific genetic or environmental factors predict disease severity, progression and response to treatment, with an overall objective of identifying new and personalised treatments for patients with this disease.

Detailed description: This is a multi-centre, observational study of children with rare inherited cardiac conditions. The focus of the study will be on children with clinically diagnosed cardiomyopathy and their unaffected parents, with collection of baseline demographic data, imaging data, and genotyping data. Children and their parents will been rolled over a 5-year period.

Sub-sets of patients with confirmed diagnoses of other heritable cardiovascular diseases with onset \<16 years will also be recruited.These will include children who following evaluation by their clinical multidisciplinary team (which will include a geneticist or genetic counsellor) are likely to have a rare monogenic condition. Other affected family members of eligible patients may be also invited to participate in the study.

Information for this study will be collected primarily from investigations performed as part of the participants' routine clinical care including whole genome sequencing commissioned by NHS England. The study will seek consent to access and export this data. Procedures performed as part of this study may include venepuncture and/or saliva collection and carry minimal risk to the patient.

Parents of participants that are recruited into the study will donate a blood sample (or saliva sample if unable to provide blood) and consent will be requested for collection of health information and results of relevant investigations carried out as part of their routine clinical care (e.g. an echocardiogram). Other family members that are recruited into the study will donate a blood sample (or saliva sample if unable to provide blood) and consent will be requested for collection of health information. Family members of deceased patients with cardiomyopathy or other inherited cardiac conditions may be asked if they wish to donate stored samples that may have been taken prior to death or as part of a post-mortem examination to establish cause of death. Any discussion with regard to the use of stored samples for this project will be initiated by the clinical care team for the deceased patient and their family to minimise any potential distress to the family. Sub-sets of patients may be asked to donate tissue samples taken as part of their clinical care.

Eligibility criteria: Inclusion Criteria:

* Males or females with a confirmed diagnosis of childhood onset (\<16 years) PCM
* Males or females with childhood onset (\<16 years) of a rare inherited cardiac condition likely to be a monogenic condition
* Capacity for parents to provide informed consent
* Genotype negative following local standard diagnostic ICC gene panel
* Family members of patients with ICC, both affected and unaffected

Exclusion Criteria:

* Parents who lack capacity to provide consent on behalf of their children/themselves
* Onset over 16 years
* Significant teratogen exposure (including maternal diabetes) likely to contribute to cardiac dysfunction (following discussion with Cardiologist)
* Significant coronary heart disease likely to contribute to cardiac dysfunction (following discussion with Cardiologist)
* Other secondary causes of cardiac dysfunction likely to explain the phenotype of the patient
* Patients with a confirmed genetic diagnosis (patients with variants of uncertain significance are not excluded).

Primary outcomes:
measure: Primary outcome measures
timeFrame: 5 years
Secondary outcomes:
Other outcomes:
Locations:
city: London
country: United Kingdom
facility: Royal Brompton Hospital
city: London
country: United Kingdom
facility: Great Ormond Street Hospital for Children
city: Uxbridge
country: United Kingdom
facility: Harefield Hospital
Study officials:
affiliation: Imperial College London
name: James Ware
role: PRINCIPAL_INVESTIGATOR
References: