Clinical trial NCT02413450: Derivation of Human Induced Pluripotent Stem (iPS) Cells to Heritable Cardiac Arrhythmias
Official title: Derivation of Human Induced Pluripotent Stem (iPS) Cells to Heritable Cardiac Arrhythmias (Long QT Syndrome, Brugada Syndrome, CPVT and Early Repolarization Syndrome)
Study type: OBSERVATIONAL
Overall status: ENROLLING_BY_INVITATION
Conditions: Inherited Cardiac Arrythmias
Long QT Syndrome (LQTS)
Brugada Syndrome (BrS)
Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT)
Early Repolarization Syndrome (ERS)
Arrhythmogenic Cardiomyopathy (AC, ARVD/C)
Hypertrophic Cardiomyopathy (HCM)
Dilated Cardiomyopathy (DCM)
Muscular Dystrophies (Duchenne, Becker, Myotonic Dystrophy)
Normal Control Subjects
Keywords: induced Pluripotent Stem Cells (iPSC)
Channelopathies
Catecholaminergic
Arrhythmogenic
Lead sponsor: Johns Hopkins University
Sponsor class: OTHER
Collaborators: name: National Heart, Lung, and Blood Institute (NHLBI)
First posted: 2015-04-10
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: FAMILY_BASED
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Participants who have a mutation causing ARVD/C or LQTS or a first degree family member with such a gene mutation. Participants, including patients with ARVD/C or LQTS and family members, who have previously been genotyped for clinically indicated reasons will be approached to join the study.

Brief summary: Human induced pluripotent stem cells (hiPSCs) have driven a paradigm shift in the modeling of human disease; the ability to reprogram patient-specific cells holds the promise of an enhanced understanding of disease mechanisms and phenotypic variability, with applications in personalized predictive pharmacology/toxicology, cell therapy and regenerative medicine. This research will collect blood or skin biopsies from patients and healthy controls for the purpose of generating cell and tissue models of Mendelian heritable forms of heart disease focusing on cardiomyopathies, channelopathies and neuromuscular diseases. Cardiomyocytes derived from hiPSCs will provide a ready source of disease specific cells to study pathogenesis and therapeutics.

Detailed description: Further study details as provided by Gordon F. Tomaselli, Johns Hopkins University:

Biospecimen Retention: Blood or tissue samples, hiPSCs and cardiomyocytes reprogrammed from hiPSCs Eligible patients will be approached and the study will be explained in full as a part of obtaining informed consent for the study. The subjects will have an opportunity to ask questions about the study. Control subjects, often but not exclusively family member that meet the eligibility criteria will undergo a similar procedure for informed consent. Subjects will be evaluated in clinic and will have a 1-3 mm skin biopsy or blood draw (30 cc). The subjects will be asked about their medical history during the clinic visit but this information will not be transmitted to the research laboratories where the iPSCs are generated and re-programmed, only the disease genotype will be associated with the samples. The samples that will be frozen and stored are whole blood, white blood cells, skin biopsies, hiPSCs and reprogrammed cardiomyocytes.

Eligibility criteria: Inclusion Criteria:

* All patients and family members 18 years of age or older with inherited cardiac arrhythmias including LQTS, Brugada Syndrome (BrS), cathecholaminergic polymorphic ventricular tachycardia (CPVT) or early repolarization syndrome (ERS) are eligible for enrollment.
* All enrolled patients will have undergone clinically indicated genetic testing.

Exclusion Criteria:

* Age \<18 years
* \>85 years
* pregnant women
* life-limiting co-morbidities
* immunocompromise

Primary outcomes:
measure: •Production of cardiomyocytes and engineered tissues from hiPSC-derived cardiomyocytes to be used in mechanistic studies of disease and testing of therapeutic interventions.
timeFrame: 10 years
Secondary outcomes:
Other outcomes:
Locations:
city: Baltimore
country: United States
facility: Johns Hopkins Medical Institute
state: Maryland
Study officials:
affiliation: Johns Hopkins University
name: Andreas Barth, MD
role: PRINCIPAL_INVESTIGATOR
References: