Congenital Heart DiseaseNCT00243776
Molecular and Cellular Characterization of Cardiac Tissue in Postnatal Development
An observational study of Congenital Heart Disease and Tetralogy of Fallot, run by Emory University at 1 site in United States.
Trial summary
The study team will use small pieces of human hearts which are removed as part of a required surgical procedure to study different objectives. One of the objective is how calcium ions pass through the membrane of heart cells in order to tell the heart cell how much force to contract with when the heart beats. Read more about this study
- Who is it for?
- Ages Up to 20 years
- Conditions the study is for
- Congenital Heart Disease, Tetralogy of Fallot
- How many people
- 600 participants
- Where
- 1 siteUnited States
- Study dates
- Apr 2005to Dec 2027
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Up to 20 years
- All sexes
- No healthy volunteers
- Child, Adult
Study population: Children undergoing surgery for repair of congenital heart disease
Who may be able to join
- Patients undergoing cardiopulmonary bypass surgery
- Patients undergoing surgery for repair of congenital heart disease such as ventricular septal defect or defective mitral or aortic valves.
Who cannot join
- Prior cardiac surgery
- History of atrial fibrillation or other atrial arrhythmias prior to operation
- History of heart failure
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
Emory University School of Medicine
Atlanta, Georgia, 30322
Mary B Wagner, PhD
About this study
The study team will use small pieces of human hearts which are removed as part of a required surgical procedure to study different objectives. One of the objective is how calcium ions pass through the membrane of heart cells in order to tell the heart cell how much force to contract with when the heart beats. Investigators will also study the proteins and RNA of these pieces to determine how the newborn heart cells control their force of contraction differently from adult heart cells. Investigators hypothesize that infant hearts have different regulation of calcium entry than adult hearts. The study team also wants to study combinations of 3D cardiac spheres with multiple environmental cues that can improve functional and metabolic maturation of Human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) and generate a more clinically relevant cell model.
Read the detailed description
Extrapolating pharmacological and surgical therapies from adult (AD) studies to infant (INF) patients is problematic because the knowledge of cellular electrophysiology and molecular biology of human INF heart cells is limited. The investigators have studied developmental differences in rabbit ventricular cells and now extend these studies to atrial and ventricular cells isolated from AD, young adult (YAD) or INF patients.
The study aims are as follows:
- Developmental differences in transient outward current of atrial cells. Investigators will extend their studies to isolated cells and tissue from YADs (age 14-20). In addition, several other accessory beta-subunits have been found in cardiac myocytes and may interact with Kv channels and regulate the function of these channels. The study team will determine relative amounts of these putative regulators of human atrial Ito to determine which correlate with developmental changes in Ito kinetics.
- Developmental differences in amplitude and regulation of calcium current in atrial cells. Investigators hypothesize that INF atrial cells have tonic inhibition of adenylyl cyclase (and thus of ICa) mediated by inhibitory G proteins, possibly related to constitutive activity of the adenosine A1 receptor, and that, compared to AD or YAD cells, have greater sensitivity to inhibitors of phosphatases and phosphodiesterases, and that developmental changes in basal ICa amplitude and beta-sympathetic modulation correlate with inhibitory G protein levels, receptor numbers for M2 and A1 receptors, and constitutive inhibitory activity.
- Modulation of atrial cell calcium transients by changes in AP waveform and developmental age. The study team will test the hypothesis that prolongation of the early repolarization phase of the after potential (AP) increases Ca2+ entry and that YAD cells have faster removal of Ca2+ from cytoplasm than INF cells and will determine if the Na- Ca2+ exchange current (INCX) is greater in INF vs. AD or YAD cells.
- Developmental differences in Ca current and transients and contractility in ventricular cells. Investigators propose that INF cells and tissue have lower basal ICa, lower potency for Isoproterenol stimulation, higher levels of Gialpha3 and A1 receptors, greater inhibitory potency for adenosine, and tonic inhibition of ICa. We also propose that the YAD cells have lower levels of NCX and lower INCX, higher levels of SERCA and faster removal of Ca2+ from the cytoplasm. Previous animal studies have indicated various developmental changes in cardiac cells. We will specifically study human postnatal developmental changes in Ito, regulation of ICa and intracellular Ca2+ transients.
- Structural, Functional and Metabolic Maturation of hPSC-CMs. Investigators propose that combinations of 3D cardiac spheres with multiple environmental cues to improve mitochondrial fatty acid oxidation (FAO or beta-oxidation) pathway will promote functional and metabolic maturation of hPSC-CMs and generate a more clinically relevant model. using tissue engineering combined with pharmacological agents to regulate signals that are involved in FAO metabolism and appropriate growth factor and hormonal signaling that mimic the microenvironment for the maturation of CMs.
- Conditions
- Congenital Heart Disease, Tetralogy of Fallot
- Medical subject headings
- Heart Defects, Congenital, Tetralogy of Fallot
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Cardiac Tissue | Cardiac tissue and cells will be obtained from participants undergoing cardiac surgical repair |
What is being measured
The primary outcome is the main question the study is designed to answer.
Calcium Current Measures
Calcium currents including transients and modulation of calcium handling by activation of different pathways in isolated cells from waste tissue obtained at the time of surgical repair for Congenital Heart Disease will be measured for the duration of the study.
Measured: Duration of Study (Up to 13 Years)
Change in structural, functional and metabolic maturation of Human pluripotent stem cell derived Cardiomyocytes (hPSC-CMs)
Change in structural, functional and metabolic maturation of Human pluripotent stem cell derived Cardiomyocytes (hPSC-CMs) is achieved using combinations of 3D cardiac spheres with multiple environmental cues to improve mitochondrial fatty acid oxidation (FAO or beta-oxidation) pathway will promote functional and metabolic maturation of hPSC-CMs and generate a more clinically relevant model. The outcome will be measured whether the cells achieved maturation (structural, functional and metabolic maturation) or not after using combinations of 3D cardiac spheres with multiple environmental cues.
Measured: Duration of Study (Up to 3 Years)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Oct 2005 (estimated)
- Study startApr 2005
- Primary completionDec 2027 (estimated)
- Study completionDec 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Congenital Heart DiseaseStudies of the same condition, open and under way.
- More trials run by Emory UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 600 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Emory University
- Sponsor type
- University, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI)
- Responsible party
- Principal investigator, Michael Davis, Emory University
- Investigators
- Michael E Davis, PhD, Principal investigator, Emory University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00243776
- Sponsor's protocol ID
- IRB00005500
- Other IDs
- R01HL077485, 35328, 2025P009622
- Status last verified
- May 2026
- First submitted
- 24 Oct 2005
- Last updated
- 6 May 2026
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- Undecided
Publications
Wiegerinck RF, Cojoc A, Zeidenweber CM, Ding G, Shen M, Joyner RW, Fernandez JD, Kanter KR, Kirshbom PM, Kogon BE, Wagner MB. Force frequency relationship of the human ventricle increases during early postnatal development. Pediatr Res. 2009 Apr;65(4):414-9. doi: 10.1203/PDR.0b013e318199093c.
PubMed 19127223
Study at a glance
From the registry record, last updated by the sponsor on 6 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Molecular and Cellular Characterization of Cardiac Tissue in Postnatal Development
- ClinicalTrials.gov ID
- NCT00243776
- Acronym / sponsor ID
- IRB00005500
- Conditions
- Congenital Heart Disease, Tetralogy of Fallot
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 600 participants (estimated)
- Lead sponsor
- Emory UniversityUniversity, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI)
- Study start
- Apr 2005
- Primary completion
- Dec 2027 (estimated)
- Study completion
- Dec 2027 (estimated)
- First posted
- 25 Oct 2005 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The study team will use small pieces of human hearts which are removed as part of a required surgical procedure to study different objectives. One of the objective is how calcium ions pass through the membrane of heart cells in order to tell the heart cell how much force to contract with when the heart beats. Investigators will also study the proteins and RNA of these pieces to determine how the newborn heart cells control their force of contraction differently from adult heart cells. Investigators hypothesize that infant hearts have different regulation of calcium entry than adult hearts. The study team also wants to study combinations of 3D cardiac spheres with multiple environmental cues that can improve functional and metabolic maturation of Human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) and generate a more clinically relevant cell model.
Detailed description
Extrapolating pharmacological and surgical therapies from adult (AD) studies to infant (INF) patients is problematic because the knowledge of cellular electrophysiology and molecular biology of human INF heart cells is limited. The investigators have studied developmental differences in rabbit ventricular cells and now extend these studies to atrial and ventricular cells isolated from AD, young adult (YAD) or INF patients.
The study aims are as follows:
- Developmental differences in transient outward current of atrial cells. Investigators will extend their studies to isolated cells and tissue from YADs (age 14-20). In addition, several other accessory beta-subunits have been found in cardiac myocytes and may interact with Kv channels and regulate the function of these channels. The study team will determine relative amounts of these putative regulators of human atrial Ito to determine which correlate with developmental changes in Ito kinetics.
- Developmental differences in amplitude and regulation of calcium current in atrial cells. Investigators hypothesize that INF atrial cells have tonic inhibition of adenylyl cyclase (and thus of ICa) mediated by inhibitory G proteins, possibly related to constitutive activity of the adenosine A1 receptor, and that, compared to AD or YAD cells, have greater sensitivity to inhibitors of phosphatases and phosphodiesterases, and that developmental changes in basal ICa amplitude and beta-sympathetic modulation correlate with inhibitory G protein levels, receptor numbers for M2 and A1 receptors, and constitutive inhibitory activity.
- Modulation of atrial cell calcium transients by changes in AP waveform and developmental age. The study team will test the hypothesis that prolongation of the early repolarization phase of the after potential (AP) increases Ca2+ entry and that YAD cells have faster removal of Ca2+ from cytoplasm than INF cells and will determine if the Na- Ca2+ exchange current (INCX) is greater in INF vs. AD or YAD cells.
- Developmental differences in Ca current and transients and contractility in ventricular cells. Investigators propose that INF cells and tissue have lower basal ICa, lower potency for Isoproterenol stimulation, higher levels of Gialpha3 and A1 receptors, greater inhibitory potency for adenosine, and tonic inhibition of ICa. We also propose that the YAD cells have lower levels of NCX and lower INCX, higher levels of SERCA and faster removal of Ca2+ from the cytoplasm. Previous animal studies have indicated various developmental changes in cardiac cells. We will specifically study human postnatal developmental changes in Ito, regulation of ICa and intracellular Ca2+ transients.
- Structural, Functional and Metabolic Maturation of hPSC-CMs. Investigators propose that combinations of 3D cardiac spheres with multiple environmental cues to improve mitochondrial fatty acid oxidation (FAO or beta-oxidation) pathway will promote functional and metabolic maturation of hPSC-CMs and generate a more clinically relevant model. using tissue engineering combined with pharmacological agents to regulate signals that are involved in FAO metabolism and appropriate growth factor and hormonal signaling that mimic the microenvironment for the maturation of CMs.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Cardiac Tissue | – | –Cardiac tissue and cells will be obtained from participants undergoing cardiac surgical repair |
Who may qualify
- Ages
- Up to 20 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
- Study population
- Children undergoing surgery for repair of congenital heart disease
Key inclusion criteria (2 listed)
- Patients undergoing cardiopulmonary bypass surgery
- Patients undergoing surgery for repair of congenital heart disease such as ventricular septal defect or defective mitral or aortic valves.
Key exclusion criteria (3 listed)
- Prior cardiac surgery
- History of atrial fibrillation or other atrial arrhythmias prior to operation
- History of heart failure
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Calcium Current Measures
Time frame: Duration of Study (Up to 13 Years)
Calcium currents including transients and modulation of calcium handling by activation of different pathways in isolated cells from waste tissue obtained at the time of surgical repair for Congenital Heart Disease will be measured for the duration of the study.
Change in structural, functional and metabolic maturation of Human pluripotent stem cell derived Cardiomyocytes (hPSC-CMs)
Time frame: Duration of Study (Up to 3 Years)
Change in structural, functional and metabolic maturation of Human pluripotent stem cell derived Cardiomyocytes (hPSC-CMs) is achieved using combinations of 3D cardiac spheres with multiple environmental cues to improve mitochondrial fatty acid oxidation (FAO or beta-oxidation) pathway will promote functional and metabolic maturation of hPSC-CMs and generate a more clinically relevant model. The outcome will be measured whether the cells achieved maturation (structural, functional and metabolic maturation) or not after using combinations of 3D cardiac spheres with multiple environmental cues.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 May 2026.
- Results publication: PubMed 19127223Wiegerinck RF, Cojoc A, Zeidenweber CM, Ding G, Shen M, Joyner RW, Fernandez JD, Kanter KR, Kirshbom PM, Kogon BE, Wagner MB. Force frequency relationship of the human ventricle increases during early postnatal development. Pediatr Res. 2009 Apr;65(4):414-9. doi: 10.1203/PDR.0b013e318199093c.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Michael E Davis, PhD principal investigator
Emory University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Congenital Heart Disease and Tetralogy of Fallot, run by Emory University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 6 May 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Michael E Davis, PhD (404-727-9858, medavis@emory.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Calcium Current Measures (time frame: Duration of Study (Up to 13 Years)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00243776, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 May 2026.