MARVEL: To Assess Safety and Efficacy of Myoblast Implantation Into Myocardium Post Myocardial Infarction

Sponsor

Bioheart, Inc. (Industry)

Overall Status

Unknown status

CT.gov ID

NCT00526253

Collaborator

(none)

170

Enrollment

Locations

Arms

5.2

Patients Per Site

Study Details

Study Description

Brief Summary

This study injects a person's own stem cells into heart muscle tissue after a person has one or more heart attacks. The purpose of the study is whether the stem cells will improve a patient's heart performance.

Condition or Disease	Intervention/Treatment	Phase
Congestive Heart Failure	Biological: MyoCell Biological: MyoCell Procedure: Hypothermosol	Phase 2/Phase 3

Detailed Description

Autologous myoblasts are harvested from a patient's skeletal muscle tissue. The myoblasts are isolated and expanded in culture in a closed system. When a sufficient number of cells are estimated they are taken from culture, packaged in a suspension and sent to the patient's interventionalist. The interventionalist uses an injection catheter via femoral artery to inject the myoblasts directly into the myocardium.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

170 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Triple (Participant, Care Provider, Investigator)

Primary Purpose:

Treatment

Official Title:

A Multicenter Study to Assess the Safety and Cardiovascular Effects of Myocell™ Implantation by a Catheter Delivery System in Congestive Heart Failure Patients Post Myocardial Infarction(s)

Study Start Date :

Sep 1, 2007

Anticipated Primary Completion Date :

Feb 1, 2019

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Low Dose Patient will undergo biopsy. Skeletal myoblasts will be cultured in growth media.	Biological: MyoCell Patient will receive injections of cultured, expanded skeletal myoblasts into the myocardium at a dose of 400 million cells.
Active Comparator: High Dose Patient will undergo biopsy. Skeletal myoblasts will be cultured in growth media.	Biological: MyoCell Patient will receive injections of cultured, expanded skeletal myoblasts into the myocardium at a dose of 800 million cells.
Placebo Comparator: Control Patient will undergo biopsy of muscle tissue and biopsy tissue will be sent to lab.	Procedure: Hypothermosol After the cell culture period of time has passed, patient's myocardium will be injected with the transport media alone. Patient will not receive any cultured myoblasts during these injections.

Arm

Intervention/Treatment

Active Comparator: Low Dose

Patient will undergo biopsy. Skeletal myoblasts will be cultured in growth media.

Biological: MyoCell

Patient will receive injections of cultured, expanded skeletal myoblasts into the myocardium at a dose of 400 million cells.

Active Comparator: High Dose

Patient will undergo biopsy. Skeletal myoblasts will be cultured in growth media.

Biological: MyoCell

Patient will receive injections of cultured, expanded skeletal myoblasts into the myocardium at a dose of 800 million cells.

Placebo Comparator: Control

Patient will undergo biopsy of muscle tissue and biopsy tissue will be sent to lab.

Procedure: Hypothermosol

After the cell culture period of time has passed, patient's myocardium will be injected with the transport media alone. Patient will not receive any cultured myoblasts during these injections.

Outcome Measures

Primary Outcome Measures

6-minute walk test [6 months]
Quality of Life Questionnaire [6 months]

Secondary Outcome Measures

Hospitalization occurrences [12 months]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 80 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Eligible patients must meet ALL of the following inclusion criteria during the screening/enrollment visit #1 and prior to being randomized into the study. Screening/enrollment visit #1 is defined to start the date the ICF is signed by the patient:

Chronic CHF, New York Heart Association (NYHA) Class II-IV;
Stable and on optimal medical management for greater or equal to 60 days as follows:
systolic and diastolic hypertension controlled in accordance with contemporary guidelines;
patient stabilized on maximum tolerated dose of beta blockers;
patient stabilized on maximum tolerated dose of angiotensin concerting enzyme (ACE) inhibitors;
patients intolerant of ACE inhibitors should be stabilized on angiotensin receptor blockers (ARB);
fluid control with diuretics and a salt restricted diet;
patients with sever symptoms of heart failure (Class III-IV) lacking contraindications to aldosterone antagonism and not on both ACE inhibitors and ARBs have been considered for such therapy.
Age 18-80;
Left ventricular ejection fraction (LVEF) at screening of less than or equal to 35 percent by multiple gaited acquisition scan (MUGA);
Need or feasibility for revascularization has been ruled out by previous coronary angiogram or ruled out to the satisfaction of the investigator via previous conventional stress study completed within 1 year of screening. The need or feasibility for revascularization will be reassessed at screening using dobutamine stress echocardiography (DSE);
Defined region of mycardial dysfunction related to previous MI involving the anterior, later, posterior or inferior walls including the apical septum (excluding the basal septum) assessed by a large area of akinesia in the left ventricle (using DSE at screening);
B-type natriuretic peptide (BNP) or NT pro-BNP is above the upper limit of normal.

Exclusion Criteria:

Non-pregnant women who are not postmenopausal, surgically sterile or not practicing an acceptable method of contraception. A female patient of child bearing potential, with a positive serum or urine pregnancy test at screening visit #1. Females refusing to exercise a reliable form of contraception;
Myocardial wall thickness of <6 mm (millimeters) in the akinetic myocardial region to be injected (using DSE at screening)
Inability to undergo a surgical biopsy of the skeletal muscle for culture of myoblasts, including any significant myopathy;
Patient will require revascularization within six months;
Patients on continuous or intermittent intravenous drug therapy;
Not fitted, or fitted within less than 90 days prior to screening visit #1, with an implantable cardioverter defibrillator (ICD);
Sustained ventricular tachycardia (VT), automatic implantable cardiodefibrillator (AICD) firing, or ventricular fibrillation (VF) within 90 days prior to screening visit #1;
Inability to perform a 6 minute walk test due to physical limitations other than HF including:
Severe peripheral vascular disease, including aortic aneurysms, leading to limited claudication;
Severe pulmonary disease or chronic obstructive pulmonary disease (COPD) limiting exercise, dependence on chronic oral steroid therapy or previously requiring mechanical ventilation;
Stroke or transient ischemic attack leading to limitations in lower extremities or occurring within 180 days prior to screening visit #1;
MI, unstable angina or percutaneous coronary intervention (PCI) within 90 days prior to screening;
having undergone CABG surgery within 150 days prior to screening visit #1;
Active myocarditis, constrictive pericarditis, restrictive, hypertrophic or congenital cardiomyopathy;
Hemodynamically significant severe primary valvular heart disease, unless corrected by a properly functional prosthetic valve;
Prior aortic valve replacement;
Systolic blood pressure (supine) ≤90 mmHg;
Resting heart rate >100 bpm;
Severe uncontrolled HF including any evidence of severe fluid overload such as peripheral edema >+2 or rales ≥1/3 the lungs' height, need for intravenous therapy for HF within 60 days of screening visit #1 or hospitalization for HF within 90 days of screening visit #1;
Patient scheduled to receive cardiac resynchronization therapy (CRT) during the study;
Expected to receive or received a cardiac transplant, surgical remodeling procedure, left ventricular assist device or cardiomyoplasty;
Six-minute walk test (6MWT) of >400 meters or Minnesota Living With Heart Failure (MLWHF) score of <20;
Hematocrit (HCT) concentration below 30% (males) or below 27% (females);
Serum creatinine greater than 2.5 mg/dL (milligrams per deciliter) or end stage renal disease;
Left ventricular mural thrombus;
Known sensitivity to gentamicin sulfate; or severe adverse reaction to nonionic radiocontrast agents;
Active infectious disease and/or known to have tested positive for human immunodeficiency virus (HIV), human t lymphotrophic virus (HTLV), hepatitis B virus (HBV), hepatitis C virus (HCV), cytomegalovirus (CMV); immunoglobulin M [IgM], and/or syphilis. If the panel includes antibodies to the HBV core antigen (HBV-cAg) and hepatitis B surface antigen (HBV-sAg), then an expert will be consulted as to patient's eligibility based on the patient's infectious status;
Patients have undergone enhanced external pulsation (EECP) tratment within the last 6 months;
Exposure to any previous experimental angiogenic therapy and/or myocardial laser therapy, or therapy with another investigational drug within 60 days of screening visit #1 or enrollment in any concurrent study that may confound the results of this study;
Known drug or alcohol dependence or any other factors which will interfere with the study conduct or interpretation of the results or in the opinion of the investigator are not suitable to participate;
Any illness other than CHF which might reduce life expectancy to less than 1 year from screening visit #1;
Recent initiation of cardiac resynchronization therapy via placement of a bi-ventricular pacemaker or bi-ventricular AICD within 180 days of study enrollment; and

30 Unwilling and/or not able to give written informed consent.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Cardiology, P.C.	Birmingham	Alabama	United States	35211
2	University of Alabama	Birmingham	Alabama	United States	35294
3	Mercy Gilbert Medical Center	Gilbert	Arizona	United States	85297
4	Arizona Heart Institute	Phoenix	Arizona	United States	85006
5	Mayo Clinic Hospital	Phoenix	Arizona	United States	85054
6	Scripps Green Hospital	La Jolla	California	United States	92037
7	UCSD Medical Center	La Jolla	California	United States	92103
8	Jim Moran Heart and Vascular Research Institute	Fort Lauderdale	Florida	United States	33317
9	University of Florida	Gainesville	Florida	United States	32610
10	University of Florida Shands	Jacksonville	Florida	United States	32209
11	University of Miami Miller School of Medicine	Miami	Florida	United States	33136
12	Florida Hospital Center Cardiovascular Center	Orlando	Florida	United States	32803
13	Emory/Crawford Long	Atlanta	Georgia	United States	30308
14	St. Joseph's Research Institute/ACRI	Atlanta	Georgia	United States	30342
15	RUSH University Medical Center	Chicago	Illinois	United States	60612
16	University of Iowa Hospitals and Clinics	Iowa City	Iowa	United States	52242
17	Ochsner Medical Center	New Orleans	Louisiana	United States	70121
18	Minneapolis Heart Institute	Minneapolis	Minnesota	United States	55407
19	Our Lady of Lourdes Medical Center	Camden	New Jersey	United States	08103
20	Gagnon Heart Hospital	Morristown	New Jersey	United States	07962
21	Newark Beth Israel Medical Center	Newark	New Jersey	United States	07112
22	Columbia University Medical Center	New York	New York	United States	10032
23	Duke University Medical Center	Durham	North Carolina	United States	27710
24	The Lindner Center	Cincinnati	Ohio	United States	45219
25	University Hospital, Case Western Reserve University	Cleveland	Ohio	United States	44106
26	Cleveland Clinic	Cleveland	Ohio	United States	44195
27	The Ohio State University Medical Center	Columbus	Ohio	United States	43210
28	University of Oklahoma	Oklahoma City	Oklahoma	United States	73104
29	University of Pittsburgh Medical Center	Pittsburgh	Pennsylvania	United States	15213
30	Stern Cardiology	Germantown	Tennessee	United States	38138
31	Texas Heart Institute	Houston	Texas	United States	77030
32	Swedish Medical Center	Seattle	Washington	United States	98122
33	St. Luke's Medical Center	Milwaukee	Wisconsin	United States	53215