Derivation of Human Induced Pluripotent Stem (iPS) Cells to Heritable Cardiac Arrhythmias

Derivation of Human Induced Pluripotent Stem (iPS) Cells to Heritable Cardiac Arrhythmias (Long QT Syndrome, Brugada Syndrome, CPVT and Early Repolarization Syndrome)

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.

Study Overview

• Status: Enrolling by invitation
• Conditions: Hypertrophic Cardiomyopathy (HCM); Long QT Syndrome (LQTS); Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT); Inherited Cardiac Arrythmias; Brugada Syndrome (BrS); Early Repolarization Syndrome (ERS); Arrhythmogenic Cardiomyopathy (AC, ARVD/C); Dilated Cardiomyopathy (DCM); Muscular Dystrophies (Duchenne, Becker, Myotonic Dystrophy); Normal Control Subjects

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.

• Study Type: Observational
• Enrollment (Estimated): 100

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States, 21287-9106
      • Johns Hopkins Medical Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

• 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.

Description

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

Study Plan

How is the study designed?

Design Details

• Observational Models: Family-Based
• Time Perspectives: Prospective

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
•Production of cardiomyocytes and engineered tissues from hiPSC-derived cardiomyocytes to be used in mechanistic studies of disease and testing of therapeutic interventions.	Whole Blood drawn on day of informed consent obtained.	10 years

Collaborators and Investigators

• Sponsor: Johns Hopkins University
• Collaborators: National Heart, Lung, and Blood Institute (NHLBI)
• Investigators: Principal Investigator: Andreas Barth, MD, Johns Hopkins University

Study record dates

Study Major Dates

• Study Start: August 1, 2013
• Primary Completion (Estimated): August 1, 2028
• Study Completion (Estimated): August 1, 2029

Study Registration Dates

• First Submitted: April 6, 2015
• First Submitted That Met QC Criteria: April 9, 2015
• First Posted (Estimated): April 10, 2015

Study Record Updates

• Last Update Posted (Estimated): January 8, 2024
• Last Update Submitted That Met QC Criteria: January 4, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: induced Pluripotent Stem Cells (iPSC); Channelopathies; Catecholaminergic; Arrhythmogenic
• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Nervous System Diseases; Disease; Congenital Abnormalities; Genetic Diseases, Inborn; Musculoskeletal Diseases; Muscular Diseases; Neuromuscular Diseases; Neurodegenerative Diseases; Aortic Valve Disease; Heart Valve Diseases; Muscular Disorders, Atrophic; Cardiac Conduction System Disease; Heredodegenerative Disorders, Nervous System; Heart Defects, Congenital; Cardiovascular Abnormalities; Cardiomegaly; Laminopathies; Myotonic Disorders; Aortic Stenosis, Subvalvular; Aortic Valve Stenosis; Syndrome; Muscular Dystrophies; Arrhythmias, Cardiac; Tachycardia; Tachycardia, Ventricular; Cardiomyopathies; Cardiomyopathy, Dilated; Myotonic Dystrophy; Cardiomyopathy, Hypertrophic; Brugada Syndrome; Long QT Syndrome
• Other Study ID Numbers: NA_00085175; 1R01HL128743-01A1 (U.S. NIH Grant/Contract)