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Investigating Hereditary Cardiac Disease by Reprogramming Skin Cells to Heart Muscle (CLUE)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01865981
Recruitment Status : Active, not recruiting
First Posted : May 31, 2013
Last Update Posted : September 4, 2019
Information provided by (Responsible Party):
Marios Stavridis, 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

Condition or disease
Eletrophysiology of iPS-derived Cardiomyocytes

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Study Type : Observational
Estimated Enrollment : 5 participants
Observational Model: Other
Time Perspective: Other
Official Title: Cellular Reprogramming as a Tool to Characterise the Cellular Electrophysiology of Familial Arrhythmia
Actual Study Start Date : June 2013
Estimated Primary Completion Date : June 2020
Estimated Study Completion Date : June 2020

Resource links provided by the National Library of Medicine

Hereditary VF
Patients with hereditary ventricular fibrillation, negative for known mutations
Patients suffering from Brugada syndrome

Primary Outcome Measures :
  1. 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 Outcome Measures :
  1. 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.

  2. 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.

Biospecimen Retention:   None Retained
Skin biopsies will be extracted and used to derive fibroblasts. These will be retained and reprogrammed to iPS cells (also to be retained). Derived cell lines are not considered a tissue under the UK Human Tissue Act

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
Arrhythmic patients participating in the Familial Arrhythmia Network Scotland (FANS)

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01865981

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United Kingdom
University of Dundee
Dundee, Angus, United Kingdom, DD1 9SY
Sponsors and Collaborators
University of Dundee
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Principal Investigator: Marios P Stavridis, PhD University of Dundee

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Responsible Party: Marios Stavridis, Senior Lecturer, University of Dundee Identifier: NCT01865981     History of Changes
Other Study ID Numbers: 2012CA04
T13/21 ( Other Grant/Funding Number: Tenovus Tayside )
First Posted: May 31, 2013    Key Record Dates
Last Update Posted: September 4, 2019
Last Verified: August 2019
Keywords provided by Marios Stavridis, University of Dundee:
iPS cells
Ventricular Fibrillation