Effect of Intramyocardial Injection of Mesenchymal Precursor Cells on Heart Function in People Receiving an LVAD

The Effect of Intramyocardial Injection of Mesenchymal Precursor Cells on Myocardial Function in LVAD Bridge to Transplant Patients

Status

Terminated

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT00927784

Enrollment

Registered

2009-06-25

Start date

2009-08-31

Completion date

2011-02-28

Last updated

2019-03-05

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Heart Failure

Keywords

Mesenchymal Precursor Cells, Left Ventricular Assist Device, LVAD, Congestive Heart Failure, Stem Cells

Brief summary

Left ventricular assist devices (LVADs) are one treatment option for people with congestive heart failure. This study will evaluate the safety of injecting mesenchymal precursor cells (MPCs) into the heart during LVAD implantation surgery and examine if injecting MPCs into the heart is effective at improving heart function.

Detailed description

Congestive heart failure is a major health problem and recent estimates indicate that end-stage heart failure with a 2-year mortality rate of 70-80% affects over 60,000 people in the United States each year. For these patients, treatment options are extremely limited. Less than 3,000 heart transplants are available each year because of the severely limited supply of donor hearts. Implantable LVADs, routinely used to support heart transplantation patients who decompensate awaiting a donor heart, were approved by the Food and Drug Administration (FDA) in 2002 for long-term support when heart transplantation is not an option. Few patients, however, achieve sufficient recovery to warrant LVAD explantation and those who do must still contend with ventricular dysfunction. MPCs are normally present in human bone marrow and have been shown to increase the development of blood vessels and new heart muscle cells. The purpose of this study is to determine the safety of injecting MPCs into the heart during LVAD implantation surgery. In addition, this study will examine whether injecting MPCs into the heart is effective at improving heart function. This study will enroll people who are on the waiting list to receive a donor heart and who are undergoing LVAD implantation surgery. Before the surgery, participants will be randomly assigned to one of two groups. One group of participants will have MPCs injected into their heart during LVAD surgery and the other group of participants will have a control solution (placebo) injected into their heart during the surgery. A portion of heart muscle removed during the surgery will be analyzed. Participants will be monitored by study researchers and blood samples will be collected 12 hours after the LVAD surgery and at 1, 7, 21, 60, and 90 days after the surgery. After that, a medical history review, physical examination, and blood collection will occur every 60 days until a heart transplant occurs or until 12 months after the LVAD implantation, whichever comes first. Heart function testing, which will include an echocardiogram, neuronal function testing, and a 6-minute walk test, will occur 60 and 90 days after the LVAD implantation, and every 2 months thereafter until a heart transplant occurs or until 12 months after the LVAD implantation, whichever comes first.

Interventions

BIOLOGICALMesenchymal Precursor cells (RevascorTM)

Participants will receive intramyocardial injections of low dose (25 million) or higher dose (75 million) MPCs (in sequential cohorts).

DRUGCryoprotective media alone

Participants will receive intramyocardial injections of cryoprotective media (placebo).

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

TRIPLE (Subject, Caregiver, Investigator)

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

Inclusion criteria

* Signed informed consent, release of medical information, and Health Insurance Portability and Accountability Act (HIPAA) documents * Age 18 years or older * If the participant 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 LVAD implantation * Female participants of childbearing potential must have a negative serum pregnancy test at screening * Admitted to the clinical center at the time of study entry * Listed with the United Network for Organ Sharing (UNOS) for heart transplantation * Clinical indication and accepted candidate for implantation of an FDA- approved LVAD as a bridge to transplantation

Exclusion criteria

* Cardiothoracic surgery within 30 days of study entry * Heart attack within 30 days of study entry * Prior heart transplantation, left ventricular (LV) reduction surgery, or cardiomyoplasty * Acute reversible cause of heart failure (e.g., myocarditis, profound hypothyroidism) * Anticipated requirement for biventricular mechanical support * Stroke within 30 days of study entry * Received investigational intervention within 30 days of study entry * Platelet count less than 100,000/uL within 24 hours of study entry * Active systemic infection within 48 hours of study entry * Presence of greater than 10% anti-human leukocyte antigen (HLA) antibody titers with known specificity to the MPC donor HLA antigens * 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) * Treatment and/or an incompleted follow-up treatment of any investigational therapy within 6 months of study entry * Active participation in other research therapy for cardiovascular repair/regeneration * Prior recipient of stem precursor cell therapy for cardiac repair * Pregnant or breastfeeding at the time of study entry

Design outcomes

Primary

Measure	Time frame
Incidence of Infectious Myocarditis	Measured within 90 days of study entry
Incidence of Myocardial Rupture	Measured within 90 days of study entry
Incidence of Neoplasm	Measured within 90 days of study entry
Incidence of Hypersensitivity Reaction	Measured within 90 days of study entry
Incidence of Immune Sensitization	Measured within 90 days of study entry

Secondary

Measure	Time frame	Description
Incidence of Cardiomyocyte Regeneration at Explant	up to 12 months	—
Assessment of LVAD Wean	up to 12 months	The secondary endpoints assessed during the LVAD wean include echocardiographic assessments, 6 minute walk, ability to tolerate wean from LVAD support, duration of ability to tolerate wean from LVAD support, and neuronal function. Measured at 60 days, 90 days, and every 60 days thereafter following LVAD implantation until heart transplantation or 12 months, whichever comes first
Incidence of Survival to Cardiac Transplantation	up to 12 months	—
Incidence of Cell Engraftment and Fate at Explant	up to 12 months	—
Incidence of Study Intervention-related Adverse Events	up to 12 months	This includes Device Malfunction-Pump Thrombus-Suspected and Internal Pump Component, Inflow, or Outflow Tract Infection
Incidence of All Serious Adverse Events	up to 12 months	—
Number of Patients Who Experienced Donor-specific HLA Sensitization	up to 12 months	Number of patients who experienced donor-specific HLA sensitization post-randomization in each treatment arm.
Incidence of Myocardial Neovascularization at Time of Explant	up to 12 months	—

Countries

United States

Participant flow

Recruitment details

80 patients with end-stage CHF and clinical indication for implantation with an FDA-approved LVAD as a bridge-to-transplant were to be enrolled. 40 patients in the low dose cohort(25M)/40 patients in the high dose cohort(75M). Trial enrollment was permanently suspended upon 10 patients enrolled in the low dose cohort due to a change in NIH funding.

Participants by arm

Arm	Count
Low Dose Cohort: Treatment Group Intramyocardial injection of study drug (25 million MPC) (Revasacor TM)at the time of LVAD implantation	8
Low Dose Cohort: Control Group Intramyocardial injection of vehicle (50% alpha-MEM/42.5% proFreeze NAO Freezing Medium/7.5%DMSO) at the time of LVAD implantation.	2
Total	10

Withdrawals & dropouts

Period	Reason	FG000	FG001
Overall Study	Death	1	0
Overall Study	Withdrawal by Subject	1	0

Baseline characteristics

Characteristic	Low Dose Cohort: Treatment Group	Total	Low Dose Cohort: Control Group
Age, Continuous	56 years STANDARD_DEVIATION 14	55 years STANDARD_DEVIATION 12	51 years STANDARD_DEVIATION 5
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants	1 Participants	0 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	7 Participants	9 Participants	2 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Asian	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Black or African American	2 Participants	2 Participants	0 Participants
Race (NIH/OMB) More than one race	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Unknown or Not Reported	2 Participants	2 Participants	0 Participants
Race (NIH/OMB) White	4 Participants	6 Participants	2 Participants
Region of Enrollment United States	8 participants	10 participants	2 participants
Sex: Female, Male Female	2 Participants	2 Participants	0 Participants
Sex: Female, Male Male	6 Participants	8 Participants	2 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	— / —	— / —
other Total, other adverse events	0 / 8	0 / 2
serious Total, serious adverse events	8 / 8	1 / 2