Investigating Hereditary Cardiac Disease by Reprogramming Skin Cells to Heart Muscle

Cellular Reprogramming as a Tool to Characterise the Cellular Electrophysiology of Familial Arrhythmia

Status

Completed

Phases

Unknown

Study type

Observational

Source

ClinicalTrials.gov

Registry ID

NCT01865981

Acronym

CLUE

Enrollment

Registered

2013-05-31

Start date

2013-06-30

Completion date

2017-06-01

Last updated

2020-07-07

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

Conditions

Eletrophysiology of iPS-derived Cardiomyocytes

Keywords

iPS cells, cardiomyocytes, Brugada, Ventricular Fibrillation, electrophysiology

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

Interventions

None listed

Study design

Observational model

OTHER

Time perspective

OTHER

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

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

Design outcomes

Primary

Measure	Time frame	Description
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

Measure	Time frame	Description
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.
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.

Countries

United Kingdom

Outcome results