Phase I Trial of Endocavitary Injection of Bone Marrow Derived CD133+ Cells in Ischemic Refractory Cardiomyopathy (RECARDIO Trial)
Study Details
Study Description
Brief Summary
The purpose of this study is to evaluate whether endocavitary intramyocardial injection of autologous bone-marrow-derived CD133+ cells is safe on the basis of number of adverse events, with follow-up assessments extending up to 1 year after enrolment.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1 |
Detailed Description
This will be a Phase I study investigating the safety and preliminary efficacy of endocavitary injection of bone-marrow-derived CD133+ cells in 15 patients with ischemic heart failure (IHF) not eligible for conventional revascularization. Patients eligible will undergo bone-marrow aspiration. On the day following bone-marrow aspiration patients will undergo fluoroscopy-based endocavitary intramyocardial injections of the target areas previously identified by gated-SPECT/CMR. CD133+ cells suspended in physiological saline supplemented with 5% human albumin solution will be injected into the myocardium via the endocardial route.
After discharge, efficacy follow-up will last 6-months safety follow-up (FU) will be extended up to 1 year.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Autologous bone marrow derived-CD133+ cells CD133+ cells (1-12x10^6) suspended in 10 ml physiological saline supplemented with 5% human albumin solution will be injected into the myocardium via the endocardial route; the whole 10 ml solution will be divided into 15-20 injections. |
Other: Autologous bone marrow derived-CD133+ cells
Cell therapy
|
Outcome Measures
Primary Outcome Measures
- Safety [1 year]
The primary objective of this study will be to evaluate whether endocavitary intramyocardial injection of autologous bone-marrow-derived CD133+ cells is safe on the basis of number of adverse events, with follow-up assessments extending up to 1 year after enrolment.
Secondary Outcome Measures
- Efficacy [6 months]
To determine the effects of autologous CD133+ cells as assessed before and 6-months after injection on a) regional myocardial perfusion on the basis of stress gated-SPECT and CMR when available; b) functional capacity on the basis of peak VO2 consumption at CPET.
Eligibility Criteria
Criteria
Inclusion Criteria:
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Ischemic heart failure not amenable to any type of revascularization procedure (percutaneous or surgical) as determined by one interventional cardiologist and one cardiovascular surgeon,
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Canadian Cardiovascular Society Angina functional class III to IV angina and/or symptoms of heart failure (NYHA score IIb to IV) under state-of-the-art maximal medical therapy,
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Left Ventricular Ejection Fraction between 20% and 45%,
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Peak V02 ≤ 21 mL/Kg/min,
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Presence of a reversible perfusion defect ≥ 10% of the left ventricular myocardium (at least 2 segments over 20) as determined by gated-SPECT, 6.18 years ≤ Age ≤ 75 years,
7.Hemodynamic stability, 8.Ability to accomplish a cardiopulmonary exercise testing, 9.Are not pregnant and do not plan to become pregnant during the study. Females with childbearing potential must provide a negative pregnancy test within 1-7 days before intervention and must be using oral or injectable contraception (non-childbearing potential is defined as post-menopausal for at least 1 year or surgical sterilization or hysterectomy at least 3 months before study start), 10.A signed consent form that has been approved by the institutional review board.
Exclusion Criteria:
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A high-risk acute coronary syndrome (ACS) or a myocardial infarction in the past 3 months,
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Presence of a documented unstable angina,
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Left ventricular thrombus, as documented by echocardiography,
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Evidence of a life-threatening arrhythmia,
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Presence of any severe mitral valve disease requiring valve replacement or reconstruction,
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Presence of a mechanical aortic valve,
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Presence of stenosis of the aortic valve, graded as ≥+2 equivalent to an orifice area of 1,5 cm2 or less,
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Presence of moderate to severe insufficiency of the aortic valve,
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A left ventricular wall thickness of <8 mm at the target site for cell injection, as assessed by 2-D echocardiography and/or cardiac MRI,
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Have a known, serious radiographic contrast allergy,
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Contraindications to bone-marrow aspiration,
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Be an organ transplant recipient,
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Have liver dysfunction, as evidenced by enzymes (AST,ALT) >3x the upper limits of normals,
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Severe renal failure (creatinine plasma levels > 2.5 mg/dl),
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A bleeding diathesis (defined as an INR greater than 1,5 not because of a reversible cause, i.e. warfarin),
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Have an hematologic abnormality without other explanation,
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Apparent infection (c-reactive protein (CPR)>30 mg/L, fever > 37 °C),
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An infectious-disease test result positive for human immunodeficiency virus (HIV), hepatitis B, or hepatitis C, treponema pallidum (VDRL), HTLV 1 and 2,
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Previous or current documented history of leukemia, myeloproliferative or myeloplastic disorders,
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Have a cardiac condition that limits lifespan to <1 y,
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A history of malignancy in the past 5 years,
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Have a history of drug or alcoholic abuse within the past 24 months,
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Be on chronic therapy with immunosuppressants,
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Pregnant or lactating status,
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Any condition that, in the judgment of the investigator, would place the patient at undue risk.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Azienda Ospedaliera San Gerardo di Monza | Monza | MB | Italy | 20900 |
| 2 | Centro Cardiologico Monzino, IRCCS | Milano | MI | Italy | 20138 |
| 3 | Azienda Ospedaliera Città della Salute e della Scienza di Torino | Torino | TO | Italy | 10126 |
Sponsors and Collaborators
- Centro Cardiologico Monzino
- Azienda Ospedaliera Città della Salute e della Scienza di Torino
- Azienda Ospedaliera San Gerardo di Monza
Investigators
- Principal Investigator: Giulio Pompilio, MD PhD, Centro Cardiologico Monzino, IRCCS
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- S225/612