Dilated Cardiomyopathy Clinical Trial
Official title:
A Phase 1 Open-Label Study of the Safety of Intravenous Allogeneic Neonatal Mesenchymal Cells (nMSCs) in Young Adult (1A) and Pediatric (1B) Patients With Dilated Cardiomyopathy (DCM)
Verified date | June 2024 |
Source | Emory University |
Contact | William Mahle, MD |
Phone | 404-256-2593 |
wmahle[@]emory.edu | |
Is FDA regulated | No |
Health authority | |
Study type | Interventional |
This is a Phase 1 study to determine the safety and efficacy of allogeneic neonatal mesenchymal stromal cells (nMSCs) for the treatment of Dilated Cardiomyopathy. The purpose of the study is to help doctors and scientists learn if allogeneic neonatal mesenchymal stromal cells (nMSCs) infusions are a safe and effective way to improve cardiac function and left ventricular ejection fraction.
Status | Not yet recruiting |
Enrollment | 36 |
Est. completion date | July 2027 |
Est. primary completion date | July 2027 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 4 Years to 30 Years |
Eligibility | Inclusion Criteria - Phase 1A: Age greater than or equal to 18 years and less than 30 years (=18 years, <30 years). - Phase 1B: Age greater than or equal to 4 years and less than 18 years (=4 years, <18 years) - Subjects must be able to sign their own consent for Phase 1A of the study. - Diagnosis of dilated cardiomyopathy (DCM) defined as - Any Congenital Cardiac Malformation with systemic ventricular systolic dysfunction; Idiopathic Cardiomyopathy; Familial/Inherited and/or Genetic Cardiomyopathy; History of Myocarditis; Acquired (Chemotherapy, Iatrogenic, Infection, Rheumatic, Nutritional); Ischemic (e.g. Kawasaki Disease, post-operative); Left ventricular noncompaction; Coronary Artery Disease - Left ventricular ejection fraction less than or equal to 45% documented by two-dimensional echocardiogram or cardiac MRI within the prior six months. - Left ventricular dilation as defined by echocardiography left ventricular and end-diastolic dimension Z score > +2.0 - Biventricular physiology with systemic left ventricle - Must receive guideline directed heart failure as defined by the American Heart Association, American College of Cardiology, and Heart Failure Society of America 118 - Have been unresponsive or poorly responsive to at least 3 months of maximum guideline directed treatments. Exclusion Criteria - Listed for heart transplantation (as UNOS status 1A) or hospitalized while waiting for transplant (while on inotropes or with ventricular assist device) - Cardiovascular surgery of percutaneous intervention to palliate or correct congenital cardiovascular malformations within 3 months of the screening visit. Patients anticipated to undergo corrective heart surgery during the 12 months after entry into Part 1A/1B. - Previous heart transplant recipient - Unoperated primary obstructive or severe regurgitant valve (aortic, pulmonary, or tricuspid) disease, or significant systemic ventricular outflow obstruction or aortic arch obstruction. - Severe mitral valve disease - Restrictive or hypertrophic cardiomyopathy - Cardiogenic shock - Currently on extracorporeal membrane oxygenation support - Ventricular assist device support - Lethal, uncontrollable arrhythmia defined as an arrhythmia resulting in hemodynamic instability requiring need for defibrillation, continuous intravenous anti-arrhythmic medication or mechanical circulatory support - Patients with persistent atrial fibrillation requiring specific pharmacotherapy - Amyloidosis - Ischemic dilated cardiomyopathy - Clinical history of malignant neoplasm within 5 years (with the exception of curatively treated basal cell carcinoma, squamous cell carcinoma, or cervical carcinoma) - Serious neurologic disorder including loss of vision, stroke, or paralysis - High-grade pulmonary embolism requiring interventional catheter procedure or pulmonary hypertension requiring use of pulmonary vasodilators including phosphodiesterase inhibitor or nitric oxide - High-grade renal failure [eGFR<45] mL/min/1.73 m2 - serum potassium >5.3 mmol/L - Multiple organ failure - Non-cardiac condition that limits life span for <1 year - Uncontrolled diabetes (HbA1c >9%) at screening - Active infection (including endocarditis) requiring pharmacotherapy - Sepsis - Active hemorrhagic disease (e.g., gastrointestinal bleeding, injury) - History of cardiac transplantation - Immune system-altering medications, or immunosuppressive therapy at the time of enrolment or within the prior 12 weeks - Dystrophin-associated cardiomyopathy confirmed by standard cardiomyopathy panel testing - Confirmed myocarditis at time of screening - Elevated LFTs greater than 2 times upper limit of normal at time of consent - Elevated WBC greater than upper limit of normal as defined by local lab at time of consent - Presence of HLA antibodies specific for therapeutic study product - History of noncompliance, alcohol abuse, recreational drug use, or incarceration within the last year - Currently pregnant or breastfeeding |
Country | Name | City | State |
---|---|---|---|
United States | Egleston Children's Hospital | Atlanta | Georgia |
United States | Emory Children's Center | Atlanta | Georgia |
United States | Emory University Hospital | Atlanta | Georgia |
United States | Hughes Spalding Children's Hospital | Atlanta | Georgia |
United States | Scottish Rite Children's Hospital | Atlanta | Georgia |
Lead Sponsor | Collaborator |
---|---|
Emory University | The Marcus Foundation |
United States,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Proportion of participants with freedom from any Common Toxicity Criteria for Adverse Events (CTCAE) Grade 3 or greater | Proportion of participants with freedom from any Common Toxicity Criteria for Adverse Events (CTCAE) Grade 3 or greater AE that is probably or related to the IP throughout the duration of the study will be recorded. Results can vary from 0 to 100% and higher proportion correlates with better outcome.
TCAE Grade 3 is defined as severe or medically significant not immediately life-threatening; hospitalization or prolongation of hospitalization. Grade 4 and 5 AEs include composite of: death, life-threatening events, initial or prolonged hospitalization, disability of permanent damage and congenital anomaly/birth defects. |
End of study, around 12 months post-intervention | |
Primary | Maximum tolerated dose (MTD) in patients with dilated cardiomyopathy | If two patients in a dosing group have a related SAE or Dose Limiting Toxicity (DLT), then the previous dosing group will be defined as MTD. | End of study, around 12 months post-intervention | |
Secondary | Change of left ventricular ejection fraction (LVEF) from baseline | Change of left ventricular ejection fraction (LVEF) between baseline, 3-month, 6-month, and 12-month follow-up determined by echocardiography and cardiac MRI. | Baseline, 3-month, 6-month, and 12-month post-intervention | |
Secondary | Change in N-terminal pro b-type natriuretic peptide (NT-proBNP) levels from baseline | N-terminal pro b-type natriuretic peptide (NT-proBNP) levels will be collected on infusion days, and all post infusion follow up visits. | Baseline, 3-month, 6-month, and 12-month post-intervention | |
Secondary | Change of 6-minute walk test (6MWT) results | A 6-minute walk test (6MWT) will be completed at baseline, 3-month, 6-month, and 1-year visits to measure functional status if the participant is developmentally appropriate. Distance in meters will be measured until the participant can either walk 6 minutes, or they become too exhausted. | Baseline, 3-month, 6-month, and 12-months post-intervention | |
Secondary | Change in quality-of-life validated survey scores in Peds Quality of Life (QOL) survey | Change in quality-of-life validated survey scores in Peds Quality of Life (QOL) survey (=4 years - < 18 years). Total possible score ranges from 0 to 100 and higher scores indicate better QOL. | Baseline, 3-month, 6-month and 12-month post-intervention | |
Secondary | Change in Kansas City Cardiomyopathy Questionnaire | Change in Kansas City Cardiomyopathy Questionnaire will be recorded (=18 years - =30 years). KCCQ scores are scaled from 0 to 100 and summarized in 25-point ranges, where scores represent health status as follows: 0 to 24: very poor to poor; 25 to 49: poor to fair; 50 to 74: fair to good; and 75 to 100: good to excellent. | Baseline, 3-month, 6-month and 12-month post-intervention |
Status | Clinical Trial | Phase | |
---|---|---|---|
Recruiting |
NCT05564689 -
Absolute Coronary Flow in Patients With Heart Failure With Reduced Ejection Fraction and Left Bundle Branch Block With Cardiac Resynchronization Therapy
|
||
Recruiting |
NCT04982081 -
Treating Congestive HF With hiPSC-CMs Through Endocardial Injection
|
Phase 1 | |
Not yet recruiting |
NCT04703751 -
Evaluation of the CIRCULATE Catheter for Transcoronary Administration of Pharmacologic and Cell-based Agents
|
N/A | |
Recruiting |
NCT01157299 -
Hemodynamic Evaluation of Preload Responsiveness in Children by Using PiCCO
|
N/A | |
Completed |
NCT00765518 -
Use of Ixmyelocel-T (Formerly Cardiac Repair Cell [CRC] Treatment) in Patients With Heart Failure Due to Dilated Cardiomyopathy (IMPACT-DCM)
|
Phase 2 | |
Completed |
NCT02115581 -
Coenzyme Q10 Supplementation in Children With Idiopathic Dilated Cardiomyopathy
|
Phase 4 | |
Recruiting |
NCT04246450 -
Arrhythmic Risk Stratification in Nonischemic Dilated Cardiomyopathy
|
N/A | |
Recruiting |
NCT05799833 -
Low QRS Voltages in Young Healthy Individuals and Athletes
|
||
Recruiting |
NCT01914081 -
Resveratrol: A Potential Anti- Remodeling Agent in Heart Failure, From Bench to Bedside
|
Phase 3 | |
Recruiting |
NCT03061994 -
Metabolomic Study of All-age Cardiomyopathy
|
N/A | |
Recruiting |
NCT02915718 -
A Clinical Study of Immunoadsorption Therapy for Dilated Cardiomyopathy
|
N/A | |
Completed |
NCT03893760 -
Assessment of Right Ventricular Function in Advanced Heart Failure
|
||
Not yet recruiting |
NCT01219452 -
Intramuscular Injection of Mesenchymal Stem Cell for Treatment of Children With Idiopathic Dilated Cardiomyopathy
|
Phase 1/Phase 2 | |
Recruiting |
NCT02175836 -
Arrhythmia Prediction Trial
|
N/A | |
Active, not recruiting |
NCT00962364 -
Long-term Evaluation of Patients Receiving Bone Marrow-derived Cell Administration for Heart Disease
|
||
Recruiting |
NCT05026112 -
The Arrhythmogenic Potential of Midwall Septal Fibrosis in Dilated Cardiomyopathy
|
||
Recruiting |
NCT05237323 -
Micophenolate Mofetil Versus Azathioprine in Myocarditis
|
Phase 3 | |
Recruiting |
NCT04649034 -
Intraventricular Stasis In Cardiovascular Disease
|
||
Suspended |
NCT03071653 -
Left Cardiac Sympathetic Denervation for Cardiomyopathy Feasibility Pilot Study
|
Phase 2 | |
Completed |
NCT02619825 -
Non-Invasive Evaluation of Myocardial Stiffness by Elastography in Pediatric Cardiology (Elasto-Pédiatrie)
|
N/A |