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Principal Investigator: Stuart Berger
Organization: LURIE CHILDREN'S HOSPITAL OF CHICAGO
Fiscal Year: 2024
Award: $408,351
Funding agency: National Heart Lung and Blood Institute
This application for the "Allogeneic Human Mesenchymal Stem Cell (MSC) Injection in Patients with Hypoplastic
Left Heart Syndrome: A Phase IIb Clinical Trial (ELPIS)" Clinical Coordinating Center (CCC) is collaborative with
the ELPIS Data Coordinating Center (DCC) application. The CCC will have ultimate responsibility for managing
the ELPIS clinical consortium of six clinical sites, meeting, planning enrollment milestones, distributing CCC
resources, and overseeing all aspects of clinical design of the studies. Hypoplastic Left Heart Syndrome (HLHS)
is one of the most complex forms of congenital heart disease (CHD), with a reported incidence of 0.2 per 1000
live births or 3% of children born with CHD. Once a universally fatal diagnosis, dramatic improvements in three
staged palliative operations now allow the single right ventricle (RV) to functionally support the circulation.
Despite these strides in medical care, the mortality rate of these infants remains as high as 25 to 35 percent
during the first year of life and continues with a high mortality rate for the rest of their life. Those surviving
childhood are likely to progress towards cardiac transplantation, usually due to failure of the systemic RV. To
address this RV dysfunction, our stem cell trial is based on a decade of basic research and the ELPIS Phase I
study using allogeneic MSCs in HLHS patients at the Stage II operation. Our completed enrolled ELPIS Phase
I study supports both the feasibility for this investigative strategy and the safety profile of the allogeneic MSCs.
Secondary endpoints demonstrated that the initial MSC treated patients showed by cardiac MRI (CMR) no
difference in RV ejection fraction, or end diastolic volumes, however a significant decrease in RV mass was
present, a surrogate for decreased hypertrophy. Our hypothesis for this trial is that intramyocardial delivery of
allogeneic MSCs will improve the performance of the single systemic RV in HLHS patients at the Stage II
operation. A total of 36 HLHS patients who are undergoing the Stage II operation will be single blinded and
randomized to either receive MSC treatment or standard of care. Patients will be followed for one year. The
primary outcome measurement will be decrease in RV mass as determined by CMR studies at baseline, 6 and
12 months following MSC injection. Secondary outcomes will include improvements in clinical and physiologic
endpoints, improvements seen by other global RV cardiac function parameters measured by serial CMR studies,
exosome biomarker analysis and safety endpoints. This single blinded randomized clinical trial is designed to
address the following specific aims: (1) to analyze MSC delivery for RV function improvement at the Stage II
operation; (2) to determine dynamic changes of the amount and composition of plasma biomarkers derived from
the transplanted MSCs; and (3) to analyze safety of MSC treatment. Although not planned as a survival study,
we anticipate that the proposed study will provide valuable data on the safety and benefit of MSC treatment in
HLHS patients. The sufficiently definitive information will inform the decision on whether to proceed with a Phase
III clinical trial of therapeutic MSC delivery to reduce mortality in HLHS patients and to direct its study design.
Terms: <0-11 years old><Address><Allogenic><Anastomosis><Anastomosis - action><Arrhythmia><Back><Basic Research><Basic Science><Biological Markers><Blood Plasma><Blood Serum><Bone-Derived Transforming Growth Factor><Cardiac><Cardiac Arrhythmia><Cardiac Malformation><Cardiac Muscle Cells><Cardiac Myocytes><Cardiac Transplantation><Cardiocyte><Cardiopulmonary Bypass><Caring><Causality><Cell secretion><Cellular Secretion><Child><Child Youth><Childhood><Children (0-21)><Circulation><Clinical><Clinical Research><Clinical Study><Clinical Trials><Complex><Computer Models><Computerized Models><Data><Data Coordinating Center><Data Coordination Center><Death Rate><Diagnosis><Dorsum><Down-Regulation><EFRAC><Ejection Fraction><Enrollment><Etiology><Failure><Family suidae><GDF15><GDF15 gene><Goals><Heart Arrhythmias><Heart Grafting><Heart Malformation><Heart Muscle Cells><Heart Transplantation><Heart myocyte><Heart-Lung Bypass><Human><Hypertrophy><Hypoplastic Left Heart Syndrome><Hypoplastic Left Ventricle><Incidence><Infant><Injections><Interrupted Aortic Arch><Ischemia><JV18><JV18-1><Life><Live Birth><MADH2><MADH2 gene><MADR2><MIC-1 gene product><MIC1><MSC transplantation><Macrophage Inhibitory Cytokine-1><Magnetic Resonance><Measures><Medical><Mesenchymal Progenitor Cell><Mesenchymal Stem Cell Transplantation><Mesenchymal Stem Cells><Mesenchymal progenitor><Mesenchymal stromal/stem cells><Milk Growth Factor><Modern Man><Myocardium><NAG-1 protein><NAG1><NSAID activated gene-1 product><NSAID-Activated Protein 1><NSAID-Regulated Protein 1><Nonsteroidal Anti-Inflammatory Drug-Activated Protein 1><Outcome><Outcome Measure><PLAB><PLAB Protein><PTGF-Beta><Pathway interactions><Patients><Performance><Phase><Phase 3 Clinical Trials><Phase I Study><Phase III Clinical Trials><Phase III study><Phosphorylation><Physiologic><Physiological><Pigs><Placental Bone Morphogenic Protein><Placental TGF-Beta><Plasma><Plasma Serum><Platelet Transforming Growth Factor><Post-Operative><Postoperative><Postoperative Period><Progenitor Cells><Prostate Differentiation Factor><Protein Phosphorylation><RNA Seq><RNA sequencing><RNAseq><Randomized><Randomized, Controlled Trials><Reporting><Research Design><Research Resources><Resources><Rest><Reticuloendothelial System, Serum, Plasma><Right Ventricles><Right Ventricular Dysfunction><Right Ventricular Hypertrophy><Right heart dysfunction><Right ventricle dysfunction><Right ventricular structure><Right-sided heart dysfunction><SMAD2><Safety><Serious Adverse Event><Serum><Severe Adverse Event><Single-Blind Study><Single-blind><Study Type><Sudden Death><Suidae><Surgeon><Swine><TGF B><TGF-beta><TGF-β><TGFbeta><TGFβ><Techniques><Testing><Therapeutic><Time><Transforming Growth Factor beta><Transforming Growth Factor-Beta Family Gene><abnormal heart development><bio-markers><biologic marker><biomarker><cardiac MRI><cardiac function><cardiac graft><cardiac magnetic resonance imaging><cardiac muscle><cardiomyocyte><causation><clinical research site><clinical site><computational modeling><computational models><computer based models><computerized modeling><congenital cardiac abnormality><congenital cardiac anomalies><congenital cardiac disease><congenital cardiac disorder><congenital cardiac malformation><congenital heart abnormality><congenital heart anomaly><congenital heart disease><congenital heart disorder><congenital heart malformation><data management and coordinating center><data management center><design><designing><disease causation><enroll><exosome><experience><function of the heart><growth differentiation factor 15><heart bypass><heart function><heart muscle><heart transplant><hypoplastic left heart><hypoplastic left syndrome><improved><inhibitor><kids><measurable outcome><meeting><meetings><member><mesenchymal stromal progenitor cells><mesenchymal-derived stem cells><miR therapy><miR-based therapeutic><miR-based therapy><miRNA therapy><miRNA-based therapeutic><miRNA-based therapy><microRNA therapy><microRNA-based therapeutic><microRNA-based therapy><mortality><mortality rate><mortality ratio><new drug treatments><new drugs><new pharmacological therapeutic><new therapeutic approach><new therapeutic intervention><new therapeutic strategies><new therapeutics><new therapy><new therapy approaches><new treatment approach><new treatment strategy><next generation therapeutics><novel><novel drug treatments><novel drugs><novel pharmaco-therapeutic><novel pharmacological therapeutic><novel therapeutic approach><novel therapeutic intervention><novel therapeutic strategies><novel therapeutics><novel therapy><novel therapy approach><operation><operations><outcome measurement><palliative><pathway><pediatric><phase 1 study><phase 3 study><phase III protocol><pig model><piglet model><porcine><porcine model><pre-clinical><pre-clinical study><preclinical><preclinical study><pressure><prevent><preventing><primary end point><primary endpoint><primary outcome><progenitor biology><progenitor cell based therapy><progenitor cell biology><progenitor cell delivery><progenitor cell therapy><progenitor cell treatment><progenitor delivery><progenitor therapy><progenitor treatment><randomisation><randomization><randomized control trial><randomized, clinical trials><randomly assigned><right ventricle hypertrophy><right ventricle remodeling><right ventricular remodeling><safety and feasibility><secondary end point><secondary endpoint><secondary outcome><serious adverse experience><serious adverse reaction><standard of care><stem and progenitor biology><stem and progenitor cell therapy><stem cell based therapy><stem cell biology><stem cell delivery><stem cell derived exosomes><stem cell exosomes><stem cell mediated therapy><stem cell therapeutics><stem cell therapy><stem cell treatment><stem cell-based therapeutic><stem cell-based treatment><stem cells><study design><suid><swine model><therapeutic miRNA><therapeutic miRs><therapeutic microRNA><transcriptome sequencing><transcriptomic sequencing><youngster>