Study to Assess the Efficacy and Safety of Transplanting Autologous Skeletal Myoblasts, Into Infarcted Heart, Using an Catheter Delivery System (CAuSMIc II)
Primary Purpose
Ischemic Cardiomyopathy
Status
Unknown status
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
myoblast
sham
Sponsored by
About this trial
This is an interventional treatment trial for Ischemic Cardiomyopathy
Eligibility Criteria
Inclusion Criteria:
- Subjects with ischemic cardiomyopathy and previous myocardial infarction
- New York Heart Association Classification III - ambulatory Class IV
- Ejection fraction < 35% as determined by any method at baseline evaluation
- Subjects could be considered for enrollment if CRT placement has occurred greater than three months previously with no clinical improvement, CRT settings are judged to be optimized and the subject continues to meet all other inclusion criteria (inadequate-responders).
- Documentation of ineligibility for coronary revascularization and/or valve repair/ replacement by review of recent left heart catheterization (within six months of baseline).
- Receiving optimally tolerated doses of standard, stable pharmacotherapy, including angiotensin-converting enzyme inhibitors, unless intolerant or contra-indicated, diuretics, ß-receptor blockers for at least one month prior to enrollment
- Severe myocardial perfusion abnormality documented by SPECT imaging, involving at least 1/3 of a vascular territory, as confirmed by core lab.
Exclusion Criteria:
- Age < 21 years or > 75 years.
- Significant coronary stenosis, as determined by the Investigator, which may potentially require percutaneous or surgical revascularization within 12 weeks of enrollment.
- Recent (within 4 weeks), documented acute coronary syndrome, i.e. (Q wave or non-Q wave infarction) or hospitalization for unstable angina.
- Documented cerebrovascular accident (stroke) or TIA within 60 days.
- Left ventricular thrombus (mobile or mural-based) as evidenced by ventriculogram or echocardiography.
- Clinically significant electrocardiographic abnormalities that may interfere with subject safety during the intracardiac mapping and injection procedure. Patients with right bundle branch block with basal septal infarction.
- Subjects with CRT placement within three months of enrollment or intent to insert CRT, or CRT settings not judged to be optimized
- High grade atrioventricular block not corrected by permanent pacemaker or ICD.
- Frequent or recurrent, ventricular tachycardia in absence of an ICD.
- Atrial fibrillation with uncontrolled ventricular response
- Significant uncorrected valvular disease, which results in additional hemodynamic compromise and/or would require valvular repair or replacement. Patients with severe aortic stenosis or status-post mitral or aortic mechanical valve replacement.
- Severe peripheral vascular disease, such that femoral access would be prohibited.
- INR > 1.5 in absence of coumadin or partial thromboplastin time (PTT) >20% above ULN, or thrombocytopenia (platelet count < 75,000).
- Significant renal dysfunction (e.g., creatinine >2.5 mg/dL) or liver disease (e.g., serum glutamic-oxaloacetic transaminases / aspartate aminotransferase SGOT/AST or serum glutamic-pyruvic transaminases/alanine aminotransferase SGPT/ALT > 4 x upper limit of normal [ULN]).
- Currently enrolled, or have been enrolled within 30 days, in another investigational drug or device study that has not completed the protocol required follow-up period.
- Subjects who have received a prior investigational stem cell or angiogenic agent.
- Subjects who have tested positive for Human Immunodeficiency Virus (HIV), Hepatitis B Virus (HBV), and/or Hepatitis C Virus (HCV).
- History of skeletal muscle disease, e.g. family history of acute or chronic skeletal muscle disease including infectious, drug-induced, familial, autoimmune and idiopathic myopathies.
- Creatine phosphokinase (CK) or lactate dehydrogenase elevated greater than three times normal or unexplained elevations of CK.
- Female subjects who are pregnant or nursing or any subject with reproductive capabilities unwilling to use effective birth control for the duration of the study period.
- Evidence of concurrent infection of any type (e.g. Elevated white blood cell count {WBC>13,000}, temperature of >38.5 C, or infiltrate on chest x-ray).
- Any other major illness, which, in the Investigator's judgment, will interfere with the subject's ability to comply with the protocol, compromises subject safety, or interferes with the interpretation of the study results.
- Idiopathic Cardiomyopathy, hypertrophic cardiomyopathy
- Subjects with ventricular wall thickness in the infarct zone of < 5 mm measured by echocardiogram at baseline.
- Patients on chronic (or chronic intermittent) IV inotropic medication. -
Sites / Locations
- Mercy Gilbert
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Sham Comparator
Arm Label
1
2
Arm Description
myoblast
sham injection procedure
Outcomes
Primary Outcome Measures
Kansas City Cardiomyopathy Questionnaire
Secondary Outcome Measures
Cardiovascular mortality
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT00626314
Brief Title
Study to Assess the Efficacy and Safety of Transplanting Autologous Skeletal Myoblasts, Into Infarcted Heart, Using an Catheter Delivery System
Acronym
CAuSMIc II
Official Title
A Multi-Center, Double-Blind, Randomized, Placebo Controlled, Trial to Assess the Efficacy, Safety and Tolerability of Transplanting Autologous Skeletal Myoblasts, Into Infarcted Myocardium, Using an Endomyocardial Delivery System
Study Type
Interventional
2. Study Status
Record Verification Date
February 2008
Overall Recruitment Status
Unknown status
Study Start Date
March 2008 (undefined)
Primary Completion Date
March 2010 (Anticipated)
Study Completion Date
August 2010 (Anticipated)
3. Sponsor/Collaborators
Name of the Sponsor
Mytogen, Inc.
4. Oversight
5. Study Description
Brief Summary
The purpose of this study is to evaluate the safety and effectiveness of injecting myoblasts (grown from your own skeletal muscle), using a catheter device, directly into the damaged heart muscle for treatment of severe heart failure.
Detailed Description
Given the limited treatment options available to patients with congestive heart failure, there is a need for alternative therapies. Autologous skeletal myoblast transplantation has been demonstrated in pre-clinical studies to be a safe and effective treatment of heart failure. Initial clinical studies have shown that autologous myoblasts can be delivered into infracted myocardium by both direct epicardial and endomyocardial injection. However, autologous skeletal myoblast transplantation via percutaneous endomyocardial injection has the potential to play a significant role in such congestive heart failure patients without the need for surgical risk and general anesthesia. Thus, a Phase 2 clinical trial is proposed in order to evaluate the effectiveness of autologous myoblast delivered by endomyocardial injection for the treatment congestive heart failure.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Ischemic Cardiomyopathy
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantOutcomes Assessor
Allocation
Randomized
Enrollment
165 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
1
Arm Type
Experimental
Arm Description
myoblast
Arm Title
2
Arm Type
Sham Comparator
Arm Description
sham injection procedure
Intervention Type
Biological
Intervention Name(s)
myoblast
Intervention Description
autologous myoblast
Intervention Type
Biological
Intervention Name(s)
sham
Intervention Description
sham injection procedure
Primary Outcome Measure Information:
Title
Kansas City Cardiomyopathy Questionnaire
Time Frame
6 months
Secondary Outcome Measure Information:
Title
Cardiovascular mortality
Time Frame
12 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
21 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Subjects with ischemic cardiomyopathy and previous myocardial infarction
New York Heart Association Classification III - ambulatory Class IV
Ejection fraction < 35% as determined by any method at baseline evaluation
Subjects could be considered for enrollment if CRT placement has occurred greater than three months previously with no clinical improvement, CRT settings are judged to be optimized and the subject continues to meet all other inclusion criteria (inadequate-responders).
Documentation of ineligibility for coronary revascularization and/or valve repair/ replacement by review of recent left heart catheterization (within six months of baseline).
Receiving optimally tolerated doses of standard, stable pharmacotherapy, including angiotensin-converting enzyme inhibitors, unless intolerant or contra-indicated, diuretics, ß-receptor blockers for at least one month prior to enrollment
Severe myocardial perfusion abnormality documented by SPECT imaging, involving at least 1/3 of a vascular territory, as confirmed by core lab.
Exclusion Criteria:
Age < 21 years or > 75 years.
Significant coronary stenosis, as determined by the Investigator, which may potentially require percutaneous or surgical revascularization within 12 weeks of enrollment.
Recent (within 4 weeks), documented acute coronary syndrome, i.e. (Q wave or non-Q wave infarction) or hospitalization for unstable angina.
Documented cerebrovascular accident (stroke) or TIA within 60 days.
Left ventricular thrombus (mobile or mural-based) as evidenced by ventriculogram or echocardiography.
Clinically significant electrocardiographic abnormalities that may interfere with subject safety during the intracardiac mapping and injection procedure. Patients with right bundle branch block with basal septal infarction.
Subjects with CRT placement within three months of enrollment or intent to insert CRT, or CRT settings not judged to be optimized
High grade atrioventricular block not corrected by permanent pacemaker or ICD.
Frequent or recurrent, ventricular tachycardia in absence of an ICD.
Atrial fibrillation with uncontrolled ventricular response
Significant uncorrected valvular disease, which results in additional hemodynamic compromise and/or would require valvular repair or replacement. Patients with severe aortic stenosis or status-post mitral or aortic mechanical valve replacement.
Severe peripheral vascular disease, such that femoral access would be prohibited.
INR > 1.5 in absence of coumadin or partial thromboplastin time (PTT) >20% above ULN, or thrombocytopenia (platelet count < 75,000).
Significant renal dysfunction (e.g., creatinine >2.5 mg/dL) or liver disease (e.g., serum glutamic-oxaloacetic transaminases / aspartate aminotransferase SGOT/AST or serum glutamic-pyruvic transaminases/alanine aminotransferase SGPT/ALT > 4 x upper limit of normal [ULN]).
Currently enrolled, or have been enrolled within 30 days, in another investigational drug or device study that has not completed the protocol required follow-up period.
Subjects who have received a prior investigational stem cell or angiogenic agent.
Subjects who have tested positive for Human Immunodeficiency Virus (HIV), Hepatitis B Virus (HBV), and/or Hepatitis C Virus (HCV).
History of skeletal muscle disease, e.g. family history of acute or chronic skeletal muscle disease including infectious, drug-induced, familial, autoimmune and idiopathic myopathies.
Creatine phosphokinase (CK) or lactate dehydrogenase elevated greater than three times normal or unexplained elevations of CK.
Female subjects who are pregnant or nursing or any subject with reproductive capabilities unwilling to use effective birth control for the duration of the study period.
Evidence of concurrent infection of any type (e.g. Elevated white blood cell count {WBC>13,000}, temperature of >38.5 C, or infiltrate on chest x-ray).
Any other major illness, which, in the Investigator's judgment, will interfere with the subject's ability to comply with the protocol, compromises subject safety, or interferes with the interpretation of the study results.
Idiopathic Cardiomyopathy, hypertrophic cardiomyopathy
Subjects with ventricular wall thickness in the infarct zone of < 5 mm measured by echocardiogram at baseline.
Patients on chronic (or chronic intermittent) IV inotropic medication. -
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
JEROMY BROWN
Phone
617-423-7999
Ext
124
Email
JBrown@ccstrials.com
Facility Information:
Facility Name
Mercy Gilbert
City
Gilbert
State/Province
Arizona
ZIP/Postal Code
85297
Country
United States
Facility Contact:
First Name & Middle Initial & Last Name & Degree
NABIL DIB, MD
12. IPD Sharing Statement
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Study to Assess the Efficacy and Safety of Transplanting Autologous Skeletal Myoblasts, Into Infarcted Heart, Using an Catheter Delivery System
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