Clinical trial NCT01666132: METHOD - Bone Marrow Derived Mononuclear Cells in Chronic Ischemic Disease
Official title: METHOD - Phase I/II Study of Intramyocardial Injection of Bone Marrow Derived Mononuclear Cells in Chronic Ischemic Disease
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: Chronic Ischemic Heart Disease
Keywords: LVEF < 40%
Lead sponsor: Cardiocentro Ticino
Sponsor class: OTHER
First posted: 2012-08-16
Enrollment: 10
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: Intramyocardial, NOGA guided injection of bone marrow derived mononuclear cells in patients with chronic ischemic heart disease and LVEF \< 40%. The primary objective is to determine whether the administration of the cells improves recovery of the left ventricular function. Secondary objective is the finding of clinical or paraclinical parameters to predict potential benefits of the treatment (basing on MRI characteristics such as size, transmurality of the myocardial infarction and peri-lesional ischemia).

In the first part of the study 10 patients are treated without control group. This phase serves as feasibility and safety part of the study.


Eligibility criteria: Inclusion Criteria:

* Chronic cardiac ischemic disease at least 4 months after one ore more myocardial infarctions in a stable phase of the disease without option for revascularization
* LVEF at echocardiography ≤ 40%
* Significant regional LV wall motion dysfunction in the infarct related territory
* Symptoms NYHA II-IV or CCS II-III (at least class III according to one of the two classifications)
* Patient agrees to comply with all follow-up evaluations
* Age \> 18 years old
* Patient has been informed of the nature of the clinical trial and agrees to its provision and has provided written informed consent

Exclusion Criteria:

* Abnormal regional wall motion outside the infarct region
* Need for revascularization in a non infarct-related coronary within 6 months
* Patient has moderate to severe aortic valve disease, aortic or mitral prosthetic valve
* Patient has a significant mitral valve insufficiency (Effective Regurgitant office - ERO - \> 0.2 cm2 with possibility of mitral valve surgery
* Left ventricular thrombus at echocardiography
* LV-aneurysma planned surgical aneurysmectomy
* LV-wall thickness \< 5mm in the target territory
* Congenital heart disorder of hemodynamic relevance
* Known active infection or chronic infection with HIV, HBV or HCV
* Chronic inflammatory disease
* Serious concomitant disease with a life expectancy of less than one year
* Follow up impossible (no fixed abode, etc)
* Contraindication for cardiac MRI (i.e. pace maker, neurostimulator, claustrophobia)
* Severe renal failure (creatinine \> 250 mmol/l)
* Relevant liver disease (GOT \> 2x norm or spontaneous INR \> 1,5)
* Anemia (Hb \< 8.5 mg/dl), Thrombocytopenia (\< 100.000/µl)
* Women of child bearing potential or pregnancy
* Participation at a clinical trial in the last 30 days

Primary outcomes:
measure: Troponin samples
timeFrame: 1 day after cell injection
measure: Number of patients with adverse events at short term
timeFrame: within 1 week after cell injection
measure: Number of patients with adverse events at mid/long term
timeFrame: up to 12 months after cell injection
Secondary outcomes:
measure: change in LVEF
timeFrame: 6 months vs. baseline
measure: change in Quality of life
timeFrame: 6 months vs. baseline
measure: change in Vo2 max
timeFrame: 6 months vs. bl
Other outcomes:
Locations:
city: Lugano
country: Switzerland
facility: Cardiocentro Ticino
Study officials:
References:
citation: Maffessanti F, Prinzen FW, Conte G, Regoli F, Caputo ML, Suerder D, Moccetti T, Faletra F, Krause R, Auricchio A. Integrated Assessment of Left Ventricular Electrical Activation and Myocardial Strain Mapping in Heart Failure Patients: A Holistic Diagnostic Approach for Endocardial Cardiac Resynchronization Therapy, Ablation of Ventricular Tachycardia, and Biological Therapy. JACC Clin Electrophysiol. 2018 Jan;4(1):138-146. doi: 10.1016/j.jacep.2017.08.011. Epub 2017 Nov 6.
citation: Surder D, Radrizzani M, Turchetto L, Cicero VL, Soncin S, Muzzarelli S, Auricchio A, Moccetti T. Combined delivery of bone marrow-derived mononuclear cells in chronic ischemic heart disease: rationale and study design. Clin Cardiol. 2013 Aug;36(8):435-41. doi: 10.1002/clc.22148. Epub 2013 May 29.