Administration of Allogeneic-MSC in Patients With Non-Ischemic Dilated Cardiomyopathy

Non-ischemic Dilated Cardiomyopathy Clinical Trial

— DCMII  

Official title:

A Phase IIB Randomized, Placebo-Controlled, Multicenter Study of the Comparative Efficacy and Safety of Administration of Allogeneic-MSC Versus Placebo in Patients With Non- Ischemic Dilated Cardiomyopathy

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04476901
• Other study ID #: 20200566
• Secondary ID: CDMRP-PR19159720
• Status: Recruiting
• Phase: Phase 2
• Start date: May 7, 2021
• Est. completion date: December 2025

Study information

• Verified date: November 2023
• Source: University of Miami
• Contact: Shelly L Sayre, MPH
• Phone: 713-500-9529
• Email: Shelly.L.Sayre[@]uth.tmc.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to evaluate the safety and effectiveness of an experimental drug called human allogeneic mesenchymal stem cell therapy.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 136
• Est. completion date: December 2025
• Est. primary completion date: December 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria:

In order to be eligible to participate in this study, an individual must meet all of the

following criteria:

1. Men and women aged 18 to 80 years (inclusive) at the time of signing the informed consent form.

2. Diagnosis of NIDCM with left ventricular ejection fraction =45%.

3. Appropriate guideline-directed optimal medical therapy for non-ischemic cardiomyopathy. At a minimum, subjects must be on beta blockers and angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) or Angiotensin Receptor Neprilysin Inhibitors (ARNI) or have appropriate medical indication precluding use of one or both of these agents. Subjects must be on a stable regimen for at least 30 days prior to the procedure. Dose titration is allowed.

4. Be a candidate for cardiac catheterization*

5. Be willing to undergo DNA test. Exclusion Criteria: An individual who meets any of the following criteria will be excluded from participation

in this study:

1. Be eligible for or require standard-of-care surgical or percutaneous intervention for the treatment of non-ischemic dilated cardiomyopathy

2. Clinical manifestation of coronary artery disease (CAD) (e.g., chest pain and concomitant clinical findings such as electrocardiogram changes suggestive of coronary ischemia, myocardial infarction) or evidence of endocardial or transmural scar on cardiac MRI suggestive of undiagnosed CAD or history of percutaneous coronary intervention (PCI) or coronary artery bypass surgery (CABG). Be indicated for or require coronary artery revascularization

3. Documented presence of epicardial stenosis of 70% or greater in one or more major epicardial coronary arteries

4. Valvular heart disease including 1) aortic valve prosthesis, mechanical mitral valve, and mitral valve clip; 2) severe aortic valve insufficiency/regurgitation within 12 months of consent*

5. Aortic stenosis with valve area = 1.5cm2*

6. Cardiomyopathy due to acute Post-partum (within 6 months), Non-compaction*, or Hypertrophic* cardiomyopathy

7. Cardiomyopathy due to known toxin (e.g amyloid) Note: anthracycline induced cardiomyopathy will be allowed

8. QTc interval > 550 ms on baseline electrocardiogram (ECG) (note: QTc interval is the interval between the start of the Q wave and the end of the T wave in the heart's electrical cycle)

9. Automated Implantable Cardioverter Defibrillator (AICD) appropriate firing or anti tachycardia pacing for ventricular tachycardia or ventricular fibrillation within 30 days prior to consent

10. Have an estimated baseline glomerular filtration rate below the clinical site's institutional cutoff

11. A hematologic abnormality during baseline testing as evidenced by hemoglobin < 9 g/dl; hematocrit < 30%; absolute neutrophil count < 2,000 or total WBC count more than 2 times upper limit of normal; or platelet values < 100,000/ul

12. Have liver dysfunction, as evidenced by enzymes Aspartate Transaminase Enzyme (AST) and Alanine Aminotransferase Enzyme (ALT) greater than three times the ULN

13. Have a bleeding diathesis or coagulopathy (International Normalised Ratio (INR) > 1.5), cannot be withdrawn from anticoagulation therapy, or will refuse blood transfusions

14. Be a solid organ transplant recipient. This does not include prior cell based therapy (>12 months prior to enrollment), bone, skin, ligament, tendon or corneal grafting.

15. Have a history of organ or cell transplant rejection

16. Have a clinical history of malignancy within the past 12 months (i.e., subjects with prior malignancy must be disease free for 12 months), except curatively treated basal cell or squamous cell carcinoma or cervical carcinoma

17. Drug and/or alcohol abuse or dependence within the past 9 months

18. Be serum positive for HIV, hepatitis B surface antigen, or viremic hepatitis C

19. Documented presence of a known Left Ventricular (LV) thrombus, aortic dissection, or aortic aneurysm. (Refer to "Guidance to the PI" section with regards to LV thrombus, below)*

20. Blood glucose levels (HbA1c) >10%

21. Severe radiographic contrast allergy

22. Known history of anaphylactic reaction to penicillin or streptomycin

23. Hypersensitivity to dimethyl sulfoxide (DMSO)

24. Non-cardiac condition with life expectancy < 1 year

25. Acute stroke or transient ischemic attack within 3 months of enrollment

26. Be pregnant, nursing, or of childbearing potential while not practicing effective contraceptive methods

27. Pacemaker-dependence with an Implantable Cardioverter Defibrillator (ICD) (Note:

pacemaker-dependent candidates without an ICD are not excluded)

28. Presence of a pacemaker and/or ICD generator with any of the following

limitations/conditions:

• manufactured before the year 2000
• leads implanted < 6 weeks prior to consent
• non-transvenous epicardial or abandoned leads
• subcutaneous ICDs
• leadless pacemakers

29. A cardiac resynchronization therapy (CRT) device implanted less than 3 months prior to consent

30. Other MRI contraindications (e.g. subject body habitus incompatible with MRI)

31. Need for advanced heart failure therapy (e.g. IV inotropes)

32. Be currently participating (or participated within the previous 30 days) in an investigational therapeutic or device trial

33. Any other condition that in the judgment of the Investigator would be a contraindication to enrollment or follow-up (*) Applies to subjects receiving product via transendocardial administration only

Related Conditions & MeSH terms

• Cardiomyopathies
• Cardiomyopathy, Dilated
• Non-ischemic Dilated Cardiomyopathy

Intervention

Biological:
• allogeneic human mesenchymal stem cells (hMSCs)
allo-hMSCs, 16-20 million cells/ml delivered at a dose of 0.5 ml/ injection x 10 injections for a total of 80-100 million allo-hMSCs or a single administration of intravenous allogeneic hMSCs (100 million).

Other:
• Placebo
Placebo will be administered as injections of plasmalyte A supplemented with 1% of 25% human serum albumin (HSA). 0.5 ml/ injection x 10 injections or an intravenous placebo infusion of Cell-free PlasmaLyte-A medium supplemented with 1% of 25% human serum albumin (HSA)

Locations

Country	Name	City	State
United States	Texas Heart Institute	Houston	Texas
United States	University of Louisville	Louisville	Kentucky
United States	University of Miami Miller School of Medicine	Miami	Florida
United States	Stanford University	Stanford	California

Sponsors (3)

Lead Sponsor	Collaborator
Joshua M Hare	The University of Texas Health Science Center, Houston, United States Department of Defense

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in LVEF	Change in Left Ventricular Ejection Fraction (LVEF) as assessed via cardiac Magnetic Resonance Imaging (MRI)	Baseline, 12 months
Secondary	Change in global ventricular strain	Change in global ventricular strain as assessed via cardiac Harmonic Phase (HARP) MRI	Baseline, 12 months
Secondary	Change in left regional strain	Change in regional ventricular strain as assessed via cardiac HARP MRI	Baseline, 12 months
Secondary	Left ventricular function concordance	The left ventricular function concordance will be measured as the Number of individuals who experienced an increase in left ventricular ejection fraction (LVEF) and a simultaneous decrease in both left ventricular end systolic volume index (LVESVI) and left ventricular end diastolic volume index (LVEDVI)	12 months
Secondary	Change in LVEDVI	Change in left ventricular end diastolic index (LVEDVI) as assessed via cardiac MRI	Baseline, 12 months
Secondary	Change in LVESVI	Change in left ventricular end systolic index (LVESVI) as assessed via cardiac MRI	Baseline, 12 months
Secondary	Change in Maximal oxygen consumption (peak VO2)	Change in maximal oxygen consumption (peak VO2) as assessed via treadmill	Baseline, 12 months
Secondary	Change in Exercise tolerance	Change in exercise tolerance as assessed as the distance covered via the six-minute walk test	Baseline, 12 months
Secondary	Change in Minnesota Living with Heart Failure Questionnaire (MLHFQ) Score	Minnesota Living with Heart Failure Questionnaire (MLHFQ) is a 21-item questionnaire with a total score ranging from 0 to 105 with lower scores indicative of better outcome.	Baseline, 12 months
Secondary	Change in New York Heart Association (NYHA) Class	NYHA Classifications of heart failure are as follows: Class I (no limitations); Class II (mild symptoms); Class III (marked limitations); Class IV (Severe limitations)	Baseline, 12 months
Secondary	Percent change in flow mediated diameter	Change in endothelial function will be reported as the percent change in flow mediated diameter assessed via flow mediated dilation (FMD).	Baseline, 12 months
Secondary	Change in EPC-CFU	Change in endothelial function will be reported as the change in Endothelial Progenitor Cell Colony Forming Unit (EPC-CFU) assessed via blood sample assay	Baseline, 12 months
Secondary	Change in N-Terminal Pro-Brain Natriuretic Peptide (NT-proBNP)	Change in NT-proBNP as assessed via blooddraw	Baseline, 12 months
Secondary	Change in cytokines	Change in NT-proBNP as assessed via blooddraw	Baseline, 12 months
Secondary	Incidence of MACE	Safety will be reported as the incidence of Major Adverse Cardiac Events (MACE) assessed by treating physician	12 months
Secondary	Incidence of TE-SAEs	Safety will be reported as the incidence of Treatment Emergent Serious Adverse Events (TE-SAEs) assessed by treating physician	Day 30

External Links

•   Cardiovascular Cell Therapy Research Network
•   DCM II Trial
•   Information on stem cells from the National Institutes of Health