Investigating Hereditary Cardiac Disease by Reprogramming Skin Cells to Heart Muscle

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

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Key information

Conditions

Eletrophysiology of iPS-derived Cardiomyocytes Arrhythmias, Cardiac Cardiovascular Diseases Heart Diseases Pathologic Processes Pathological Conditions, Signs and Symptoms Ventricular Fibrillation

Age range

18 year and older

Sex eligibility

All sexes

Study type

Observational

Primary location

University of Dundee

Dundee, Angus, DD1 9SY, United Kingdom

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Primary outcomes

Derivation of iPS cells

Time frame: 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 outcomes

Differentiation of iPS cells to cardiomyocytes

Time frame: 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

Time frame: 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.

Sponsors and collaborators

Lead sponsor

University of Dundee

Other

Registry information

Official study title

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

Acronym: CLUE

Important dates

Study start: 2013
Primary completion: 2017
Study completion: 2017
First posted: May 31, 2013
Registry last updated: Jul 7, 2020

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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