Investigating Hereditary Cardiac Disease by Reprogramming Skin Cells to Heart Muscle

Completed

• Conditions: Eletrophysiology of iPS-derived Cardiomyocytes

• Registration Number: NCT01865981
• Lead Sponsor: University of Dundee

Brief Summary

Hereditary cardiac arrhythmias (genetically caused disturbances of heart rhythm) are life threatening conditions affecting otherwise healthy young individuals. Due to the inaccessibility of heart tissue, the abnormal electrical current(s) in the heart cells causing the rhythm disturbance can be difficult to study in detail and therefore in many cases remain untreatable. The investigators propose to study heart cell electrical function from such patients by reprogramming skin cells to become stem cells and then differentiating them to heart muscle cells.

The hypothesis of the study is that the differentiated cardiac cells will display electrical abnormalities dependent on the mutation causing the disease. These abnormalities can therefore provide a clue as to the nature of the mutation causing the disease or information about its effective management

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2013-05-15
• Study First Submitted QC: 2013-05-27
• Study First Posted: 2013-05-31
• Study Start: 2013-06
• Primary Completion: 2017-06-01
• Study Completion: 2017-06-01
• Status Verified: 2020-07
• Last Update Submitted: 2020-07-02
• Last Update Posted: 2020-07-07

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 2

Inclusion Criteria

• Clinical features of Brugada Syndrome (ECG findings)
• mutation positive or mutation negative
• Idiopathic ventricular fibrillation

Exclusion Criteria

• not able to give informed consent
• Age less than 18 years
• clinical diagnosis ambiguous

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Derivation of iPS cells	12 months	Induced pluripotent cells will be derived from all participants in the study. Differences in the efficiency of iPS cell generation from different patients will be recorded, and correlated with disease status and age. iPS cell generation will be confirmed by pluripotency markers (stable endogenous gene expression of Nanog, Oct4, Sox2; colony formation; expression of SSEA4) and ability to differentiate in the absence of self-renewal stimulus (ability to self-renew in the absence of self-renewal stimulus -loss of markers above)

Secondary Outcome Measures

Name	Time	Method
Electrophysiology on iPS-derived cardiomyocytes	12 months	Ability to collect electrophysiological measurements from iPS-derived cardiomyocytes will be asssessed. Resting membrane potential, Ca2+, K+ current function and sponteneous and induced depolarisation will be measured per line and per patient. Correlations with patient disease phenotype will be recorded.
Differentiation of iPS cells to cardiomyocytes	12 months	The ability of each iPS cell line to differentiate into spontaneously beating cardiomyocytes will be assessed. Efficiency of differentiation per lina and per patient will be recorded.

Trial Locations

Locations (1)

University of Dundee; 🇬🇧 Dundee, Angus, United Kingdom