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

NCT ID: NCT04476901

Last Updated: 2025-09-12

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE2

Total Enrollment

136 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-05-07

Study Completion Date

2025-12-31

Brief Summary

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

Detailed Description

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Conditions

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Non-ischemic Dilated Cardiomyopathy

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Genotype A administered with placebo Group

Participants whose blood genotyping resulted with Genotype A (absence of any variant/ presence of benign variant) and randomized to the placebo group will receive the placebo intervention.

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type OTHER

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)

Genotype A administered with hMSC Group

Participants whose blood genotyping resulted with Genotype A (absence of any variant/ presence of benign variant) and randomized to the treatment group will receive the hMSC intervention.

Group Type EXPERIMENTAL

allogeneic human mesenchymal stem cells (hMSCs)

Intervention Type BIOLOGICAL

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).

Genotype B administered with placebo Group

Participants whose blood genotyping resulted with Genotype B (variants of uncertain significance) and randomized to the placebo group will receive the placebo intervention.

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type OTHER

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)

Genotype B administered with hMSC Group

Participants whose blood genotyping resulted with Genotype B (variants of uncertain significance) and randomized to the treatment group will receive the hMSC intervention.

Group Type EXPERIMENTAL

allogeneic human mesenchymal stem cells (hMSCs)

Intervention Type BIOLOGICAL

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).

Genotype C administered with placebo Group

Participants whose blood genotyping resulted with Genotype C (pathogenic or likely pathogenic variants) and randomized to the placebo group will receive the placebo intervention.

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type OTHER

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)

Genotype C administered with hMSC Group

Participants whose blood genotyping resulted with Genotype C (pathogenic or likely pathogenic variants) and randomized to the treatment group will receive the hMSC intervention.

Group Type EXPERIMENTAL

allogeneic human mesenchymal stem cells (hMSCs)

Intervention Type BIOLOGICAL

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).

Interventions

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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).

Intervention Type BIOLOGICAL

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)

Intervention Type OTHER

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Maximum Eligible Age

80 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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United States Department of Defense

FED

Sponsor Role collaborator

The University of Texas Health Science Center, Houston

OTHER

Sponsor Role collaborator

Joshua M Hare

OTHER

Sponsor Role lead

Responsible Party

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Joshua M Hare

Principal Investigator

Responsibility Role SPONSOR_INVESTIGATOR

Principal Investigators

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Joshua Hare, MD

Role: PRINCIPAL_INVESTIGATOR

University of Miami

Locations

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Stanford University

Stanford, California, United States

Site Status RECRUITING

University of Miami Miller School of Medicine

Miami, Florida, United States

Site Status RECRUITING

University of Louisville

Louisville, Kentucky, United States

Site Status RECRUITING

Texas Heart Institute

Houston, Texas, United States

Site Status RECRUITING

Countries

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United States

Central Contacts

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Shelly L Sayre, MPH

Role: CONTACT

713-500-9529

Lina Caceres

Role: CONTACT

305-243-5399

Facility Contacts

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Fouzia Khan, MBBS

Role: primary

650-736-1410

Ashwini Narayana

Role: backup

Lina Caceres

Role: primary

305-243-5399

Jairo Tovar

Role: backup

305-243-5399

Heidi Wilson

Role: primary

502-540-3721

Michelle Unseld

Role: backup

502-540-3423

Nichole Piece

Role: primary

832-355-9173

Sylvia Carranza

Role: backup

832-355-8524

Related Links

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https://www.cctrn.org

Cardiovascular Cell Therapy Research Network

https://stemcells.nih.gov/

Information on stem cells from the National Institutes of Health

Other Identifiers

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CDMRP-PR191597

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

20-02-134

Identifier Type: OTHER

Identifier Source: secondary_id

20200566

Identifier Type: -

Identifier Source: org_study_id

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