The Effect of Intramyocardial Injection of Mesenchymal Precursor Cells on Myocardial Function in Patients Undergoing LVAD Implantation

• Sponsor: Deborah Ascheim (Other)
• Overall Status: Completed
• CT.gov ID: NCT01442129
• Collaborator: National Heart, Lung, and Blood Institute (NHLBI) (NIH)
• Enrollment: 30
• Locations: 11
• Arms: 2
• Duration (Months): 16
• Patients Per Site: 2.7
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

The main purpose of this research is to determine whether injecting mesenchymal precursor cells (MPC) into the heart during surgery to implant a left ventricular assist device (LVAD) is safe. MPCs are normally present in human bone marrow, and have been shown to increase the development of blood vessels and new heart muscle cells in the heart. In addition, this research is being done to test whether injecting the MPCs into the heart is effective in improving heart function.

Condition or Disease	Intervention/Treatment	Phase
Heart Failure; Cardiomyopathy; Ventricular Dysfunction	Biological: MPC Intramyocardial injection; Biological: Control Solution	Phase 2

Detailed Description

Intramyocardial injection of mesenchymal precursor cells (MPC) in patients with advanced heart failure who are treated with left ventricular assist device (LVAD) implantation may result in a renewable source of proliferating functional cardiomyocytes, as well as induce development of capillaries and larger size blood vessels to supply oxygen and nutrients to endogenous myocardium and newly-implanted cardiomyocytes, and release factors capable of paracrine signaling. If safety is established and an efficacy signal is observed in this exploratory trial, then the investigators will design a follow-up trial (stage 2) based on an adaptive design. The next trial would randomize patients to active therapy at one of two doses (25 and 75 million MPCs) versus placebo, and based on a predetermined selection criterion drop randomization to one of the dose arms as results accrue. Should this exploratory trial demonstrate safety but no signal of efficacy, then the subsequent trial would be based on a single dose of 75 million MPCs versus placebo.

Study Design

• Study Type: Interventional
• Actual Enrollment: 30 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: LVAD Therapy: Exploring the Effect of Intramyocardial Injection of Mesenchymal Precursor Cells on Myocardial Function
• Study Start Date: Apr 1, 2012
• Actual Primary Completion Date: Mar 1, 2013
• Actual Study Completion Date: Aug 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: MPC Intramyocardial injection Intramyocardial injections of 25 million Mesenchymal Precursor Cells (MPCs)	Biological: MPC Intramyocardial injection; Intramyocardial injection of 25 million mesenchymal precursor cells at the time of LVAD implantation; Other Names: RevascorTM
Sham Comparator: Control Solution Intramyocardial injections of 50% Alpha-MEM/42.5% ProFreeze NAO Freezing Medium/7.5% DMSO	Biological: Control Solution; Injection of control solution during the LVAD implantation.; Other Names: Cryoprotective media

Outcome Measures

Primary Outcome Measures

1. Intervention Related Adverse Events [90 days]

   The primary safety endpoint of this study is the incidence of the following potential study-intervention related adverse events within 90 days post intervention (LVAD implantation + intramyocardial injection of study product): infectious myocarditis, myocardial rupture, neoplasm, hypersensitivity reaction, and immune sensitization.

Secondary Outcome Measures

1. Functional Status and Ventricular Function [90 days]

   The key efficacy endpoint of this study is functional status and ventricular function, while weaned from LVAD support, at 90 days post intervention (LVAD implantation + intramyocardial injection of study product). Functional status is defined by the ability to tolerate wean from LVAD support for 30 minutes without signs or symptoms of hypoperfusion, including, but not limited to symptoms of low output or signs of vascular congestion. Ventricular function will be assessed by transthoracic echocardiogram (TTE) in those patients able to be weaned for 30 minutes from LVAD support. The number of participants who successfully tolerated the 30 minute wean from LVAD support at 90 days is reported.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Signed informed consent, inclusive of release of medical information, and Health Insurance Portability and Accountability Act (HIPAA) documentation;

• Age 18 years or older;

• If the subject or partner is of childbearing potential, he or she must be willing to use adequate contraception (hormonal or barrier method or abstinence) from the time of screening and for a period of at least 16 weeks after procedure;

• Female subjects of childbearing potential must have a negative serum pregnancy test at screening;

• Admitted to the clinical center at the time of randomization;

• Clinical indication and accepted candidate for implantation of an FDA approved implantable, non-pulsatile LVAD as a bridge to transplantation or for destination therapy.

Exclusion Criteria:

• Planned percutaneous LVAD implantation;

• Anticipated requirement for biventricular mechanical support;

• Cardiothoracic surgery within 30 days prior to randomization;

• Myocardial infarction within 30 days prior to randomization;

• Prior cardiac transplantation, LV reduction surgery, or cardiomyoplasty;

• Acute reversible cause of heart failure (e.g. myocarditis, profound hypothyroidism);

• Stroke within 30 days prior to randomization;

• Platelet count < 100,000/ul within 24 hours prior to randomization;

• Active systemic infection within 48 hours prior to randomization;

• Presence of >10% anti-human leukocyte antigen (anti-HLA) antibody titers with known specificity to the MPC donor HLA antigens;

• A known hypersensitivity to dimethyl sulfoxide (DMSO), murine, and/or bovine products;

• History of cancer prior to screening (excluding basal cell carcinoma);

• Acute or chronic infectious disease, including but not limited to human immunodeficiency virus (HIV);

• Received investigational intervention within 30 days prior to randomization;

• Treatment and/or an incompleted follow-up treatment of any investigational cell based therapy within 6 months prior to randomization;

• Active participation in other research therapy for cardiovascular repair/regeneration;

• Prior recipient of stem precursor cell therapy for cardiac repair;

• Pregnant or breastfeeding at time of randomization.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Florida	Gainsville	Florida	United States	32610
2	University of Maryland	Baltimore	Maryland	United States	21201
3	Minneapolis Heart Institute Foundation	Minneapolis	Minnesota	United States	55407
4	Montefiore Einstein Heart Center	Bronx	New York	United States	10467
5	Columbia University Medical Center	New York	New York	United States	10032
6	Duke University	Durham	North Carolina	United States	27710
7	Cleveland Clinic Foundation	Cleveland	Ohio	United States	44195
8	Ohio State University	Columbus	Ohio	United States	43210
9	University of Pennsylvania	Philadelphia	Pennsylvania	United States	19104
10	Baylor Research Institute	Dallas	Texas	United States	75230
11	Texas Heart Institute	Houston	Texas	United States	77030

Sponsors and Collaborators

• Deborah Ascheim
• National Heart, Lung, and Blood Institute (NHLBI)

Investigators

• Study Chair: Timothy Gardner, MD, Christiana Care Health Services
• Study Chair: Patrick O'Gara, MD, Brigham and Women's Hospital

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Cardiothoracic Surgical Network Website

Publications

None provided.

• Responsible Party: Deborah Ascheim, Associate Professor, Clinical Director of Research, InCHOIR, Icahn School of Medicine at Mount Sinai
• ClinicalTrials.gov Identifier: NCT01442129
• Other Study ID Numbers: GCO 08-1078-00006; U01HL088942; U01HL088942-04; 711
• First Posted: Sep 28, 2011
• Last Update Posted: May 1, 2015
• Last Verified: Apr 1, 2015

• Keywords provided by Deborah Ascheim, Associate Professor, Clinical Director of Research, InCHOIR, Icahn School of Medicine at Mount Sinai: Heart Failure; Left Ventricular Assist Device; Heart Transplantation; Cardiomyopathy; Destination Therapy; Cell Therapy
• Additional relevant MeSH terms: Heart Failure; Cardiomyopathies; Ventricular Dysfunction

Study Results

Participant Flow

Recruitment Details	The trial was conducted in 11 U.S. centers with a Data and Clinical Coordinating Center (DCC); International Center for Health Outcomes and Innovation Research [InCHOIR], Icahn School of Medicine at Mount Sinai under an investigational new drug application. Enrollment began in May 2012, and the last patient was enrolled in August 2012.

Arm/Group Title	MPC Intramyocardial Injection	Control Solution
Arm/Group Description	Intramyocardial injections of 25 million MPCs Mesenchymal Precursor Cell Injection: Intramyocardial injection of 25 million mesenchymal precursor cells at the time of LVAD implantation	Intramyocardial injections of 50% Alpha-MEM/42.5% ProFreeze NAO Freezing Medium/7.5% DMSO 50% Alpha-MEM/42.5% ProFreeze NAO Freezing Medium/7.5% DMSO: Injection of control solution during the LVAD implantation.
Period Title: Overall Study
STARTED	20	10
COMPLETED	20	10
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	MPC Intramyocardial Injection	Control Solution	Total
Arm/Group Description	Intramyocardial injections of 25 million MPCs Mesenchymal Precursor Cell Injection: Intramyocardial injection of 25 million mesenchymal precursor cells at the time of LVAD implantation	Intramyocardial injections of 50% Alpha-MEM/42.5% ProFreeze NAO Freezing Medium/7.5% DMSO 50% Alpha-MEM/42.5% ProFreeze NAO Freezing Medium/7.5% DMSO: Injection of control solution during the LVAD implantation.	Total of all reporting groups
Overall Participants	20	10	30
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	55.1 (15.4)	62.2 (7.8)	57.4 (13.6)
Sex: Female, Male (Count of Participants)
Female	3 15%	2 20%	5 16.7%
Male	17 85%	8 80%	25 83.3%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	1 5%	0 0%	1 3.3%
Not Hispanic or Latino	19 95%	10 100%	29 96.7%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	6 30%	2 20%	8 26.7%
White	14 70%	8 80%	22 73.3%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	20 100%	10 100%	30 100%
Cardiomyopathy (participants) [Number]
Ischemic	7 35%	4 40%	11 36.7%
Non-Ischemic	13 65%	6 60%	19 63.3%
Indication for LVAD (participants) [Number]
Bridge to Transplantation	7 35%	3 30%	10 33.3%
Destination Therapy	13 65%	7 70%	20 66.7%

Outcome Measures

1. Primary Outcome

Title	Intervention Related Adverse Events
Description	The primary safety endpoint of this study is the incidence of the following potential study-intervention related adverse events within 90 days post intervention (LVAD implantation + intramyocardial injection of study product): infectious myocarditis, myocardial rupture, neoplasm, hypersensitivity reaction, and immune sensitization.
Time Frame	90 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	MPC Intramyocardial Injection	Control Solution
Arm/Group Description	Intramyocardial injections of 25 million MPCs Mesenchymal Precursor Cell Injection: Intramyocardial injection of 25 million mesenchymal precursor cells at the time of LVAD implantation	Intramyocardial injections of 50% Alpha-MEM/42.5% ProFreeze NAO Freezing Medium/7.5% DMSO 50% Alpha-MEM/42.5% ProFreeze NAO Freezing Medium/7.5% DMSO: Injection of control solution during the LVAD implantation.
Measure Participants	20	10
Number [events]	0	0

2. Secondary Outcome

Title	Functional Status and Ventricular Function
Description	The key efficacy endpoint of this study is functional status and ventricular function, while weaned from LVAD support, at 90 days post intervention (LVAD implantation + intramyocardial injection of study product). Functional status is defined by the ability to tolerate wean from LVAD support for 30 minutes without signs or symptoms of hypoperfusion, including, but not limited to symptoms of low output or signs of vascular congestion. Ventricular function will be assessed by transthoracic echocardiogram (TTE) in those patients able to be weaned for 30 minutes from LVAD support. The number of participants who successfully tolerated the 30 minute wean from LVAD support at 90 days is reported.
Time Frame	90 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	MPC Intramyocardial Injection	Control Solution
Arm/Group Description	Intramyocardial injections of 25 million MPCs Mesenchymal Precursor Cell Injection: Intramyocardial injection of 25 million mesenchymal precursor cells at the time of LVAD implantation	Intramyocardial injections of 50% Alpha-MEM/42.5% ProFreeze NAO Freezing Medium/7.5% DMSO 50% Alpha-MEM/42.5% ProFreeze NAO Freezing Medium/7.5% DMSO: Injection of control solution during the LVAD implantation.
Measure Participants	20	10
Number [participants]	10 50%	2 20%

Adverse Events

Time Frame	Adverse event data were collected for 12 months following randomization
Adverse Event Reporting Description	An independent Clinical Events Committee adjudicated adverse events and causes of death. Bleeding events were defined by transfusion of ≥ 4 units of packed cells within any 24 hour period during the first 7 days post LVAD implantation, and any transfusion of packed cells within any 24 hour period thereafter.
Arm/Group Title	MPC Intramyocardial Injection		Control Solution
Arm/Group Description	Intramyocardial injections of 25 million MPCs Mesenchymal Precursor Cell Injection: Intramyocardial injection of 25 million mesenchymal precursor cells at the time of LVAD implantation		Intramyocardial injections of 50% Alpha-MEM/42.5% ProFreeze NAO Freezing Medium/7.5% DMSO 50% Alpha-MEM/42.5% ProFreeze NAO Freezing Medium/7.5% DMSO: Injection of control solution during the LVAD implantation.
All Cause Mortality
	MPC Intramyocardial Injection		Control Solution
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	MPC Intramyocardial Injection		Control Solution
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	19/20 (95%)		9/10 (90%)
Blood and lymphatic system disorders
Hemolysis	1/20 (5%)	1	2/10 (20%)	2
Venous Thromboembolism	1/20 (5%)	1	1/10 (10%)	1
Cardiac disorders
Cardiac Arrrest	1/20 (5%)	1	0/10 (0%)	0
Pericardial Fluid Collection	3/20 (15%)	3	0/10 (0%)	0
Right Heart Failure	3/20 (15%)	3	3/10 (30%)	3
Sustained Ventricular Arrhythmia	2/20 (10%)	2	2/10 (20%)	2
Sustained Supraventricular Arrhythmia	2/20 (10%)	2	2/10 (20%)	2
General disorders
Major Bleeding	8/20 (40%)	71	5/10 (50%)	30
Baker's Cyst	0/20 (0%)	0	1/10 (10%)	1
Elevated WBC, LDH	1/20 (5%)	1	0/10 (0%)	0
Shortness of Breath	0/20 (0%)	0	1/10 (10%)	1
Rib Pain	1/20 (5%)	1	0/10 (0%)	0
Sub-therapeutic Anticoagulation	3/20 (15%)	4	0/10 (0%)	0
Hepatobiliary disorders
Hepatic Dysfunction	1/20 (5%)	1	0/10 (0%)	0
Infections and infestations
Major Infection - Localized Non-Device Infection	4/20 (20%)	4	2/10 (20%)	2
Major Infection - Internal Pump Component Inflow or Outflow Tract Infection	1/20 (5%)	1	0/10 (0%)	0
Sepsis	3/20 (15%)	3	1/10 (10%)	1
Major Infection	1/20 (5%)	1	0/10 (0%)	0
Injury, poisoning and procedural complications
Device Malfunction - Pump Failure	1/20 (5%)	1	0/10 (0%)	0
Intraoperative Bleeding	2/20 (10%)	2	1/10 (10%)	1
Device Malfunction - Non Pump Failure	3/20 (15%)	3	0/10 (0%)	0
Device Malfunction - Pump Thrombus Suspected	1/20 (5%)	1	1/10 (10%)	1
Device Malfunction - Pump Thrombus Confirmed	3/20 (15%)	4	1/10 (10%)	1
Nervous system disorders
Neurological Dysfunction - Other	1/20 (5%)	1	0/10 (0%)	0
TIA	1/20 (5%)	1	0/10 (0%)	0
Ischemic Stroke	1/20 (5%)	1	0/10 (0%)	0
Hemorrhagic Stroke	0/20 (0%)	0	1/10 (10%)	1
Toxic Metabolic Encephalopathy	2/20 (10%)	2	0/10 (0%)	0
Renal and urinary disorders
Acute Renal Dysfunction	4/20 (20%)	4	1/10 (10%)	1
Chronic Renal Dysfunction	1/20 (5%)	1	0/10 (0%)	0
Respiratory, thoracic and mediastinal disorders
Respiratory Failure	5/20 (25%)	5	2/10 (20%)	2
Pleural Effusion	1/20 (5%)	1	0/10 (0%)	0
Other (Not Including Serious) Adverse Events
	MPC Intramyocardial Injection		Control Solution
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	7/20 (35%)		4/10 (40%)
Blood and lymphatic system disorders
Hemolysis	2/20 (10%)	2	0/10 (0%)	0
Venous Thromboembolism	1/20 (5%)	2	0/10 (0%)	0
Cardiac disorders
Sustained Supraventricular Arrhythmia	3/20 (15%)	3	0/10 (0%)	0
Gastrointestinal disorders
Ileus	1/20 (5%)	1	0/10 (0%)	0
Hepatobiliary disorders
Hepatic Dysfunction	1/20 (5%)	1	1/10 (10%)	1
Infections and infestations
Localized Non-Device Infection	3/20 (15%)	5	2/10 (20%)	2
Renal and urinary disorders
Acute Renal Dysfunction	0/20 (0%)	0	1/10 (10%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.