A CELL-based platform to study the role of the micRotubule network in pediatric inHeritable arrhYTHMia patients and Improve the effiCacy of drug treatment

A CELL-based platform to study the role of the micRotubule network in pediatric inHeritable arrhYTHMia patients and Improve the effiCacy of drug treatment - CELLRHYTHMIC STUDY

Status

Recruiting

Phases

Unknown

Study type

Observational

Source

NL-OMON

Registry ID

NL-OMON54599

Enrollment

Registered

2018-07-09

Start date

2018-12-14

Completion date

Unknown

Last updated

2024-04-15

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

cardiac arrhythmia and sudden cardiac death

Interventions

None listed

Eligibility

Age

No minimum to 17 Years

Inclusion criteria

Inclusion criteria: In order to be eligible to participate in this study, a subject must meet all of the following criteria: - Age >= 0.5 and

Exclusion criteria

Exclusion criteria: A potential subject patient population or control who meets any of the following criteria will be excluded from participation in this study: - Non-consent for the collection of blood - Presence of any other (anatomic) cardiac disease or cardiac conduction disturbance other than the ones described for the inclusion criteria. - Additional known genetic mutations other than the ones described for the inclusion criteriaIn addition to the above exclusion criteria, healthy controls will be excluded if - they have a positive family history for a potential inheritable arrhythmia syndrome defined as a positive family history for SCD

Design outcomes

Primary

Measure	Time frame
Spontaneous cellular contractions, electrical conduction and calcium oscillations in induced cardiomyocytes will be measured. Using fluorescence-based microscopy experiments, the effect of altered microtubule dynamics on electrical conduction will be studied as well as on the localization of important proteins and protein-protein interactions in the intercalated disk. We will test the efficacy of novel drugs by performing the same measurements. We will perform T2C measurements, RNA-Sequencing, and a modified form of RNA-Sequencing called Ribo-Seq, in order to study the transcription factor-based regulation of SCN5A expression, general molecular mechanism underlying the function of SCN5A, and molecular consequences of its dysfunction in arrhythmia patients. The induced cardiomyocytes data will be correlated to the clinical phenotype of the patients investigated by ECG, 24-hours 12-lead Holter monitoring, ECG during exercise testing, ECG during fever or ECG during Ajmaline testing, Signal Averaged ECG and echocardiography. Due to the explorative nature of laboratory molecular research (statistical consultation provided by Prof. dr. ir. H. Boersma, professor in clinical epidemiology of cardiovascular disease), endpoints of change in certain parameters cannot be given yet.	—

Measure

Time frame

Spontaneous cellular contractions, electrical conduction and calcium oscillations in induced cardiomyocytes will be measured. Using fluorescence-based microscopy experiments, the effect of altered microtubule dynamics on electrical conduction will be studied as well as on the localization of important proteins and protein-protein interactions in the intercalated disk. We will test the efficacy of novel drugs by performing the same measurements. We will perform T2C measurements, RNA-Sequencing, and a modified form of RNA-Sequencing called Ribo-Seq, in order to study the transcription factor-based regulation of SCN5A expression, general molecular mechanism underlying the function of SCN5A, and molecular consequences of its dysfunction in arrhythmia patients. The induced cardiomyocytes data will be correlated to the clinical phenotype of the patients investigated by ECG, 24-hours 12-lead Holter monitoring, ECG during exercise testing, ECG during fever or ECG during Ajmaline testing, Signal Averaged ECG and echocardiography. Due to the explorative nature of laboratory molecular research (statistical consultation provided by Prof. dr. ir. H. Boersma, professor in clinical epidemiology of cardiovascular disease), endpoints of change in certain parameters cannot be given yet.

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Countries

Netherlands

Outcome results