Clinical trial NCT01049867: CD133+ Cell Therapy for Refractory Coronary Heart Disease
Official title: Phase 1-2 Study of Intracoronary Infusion of CD133+ Endothelial Precursor Cells for Patients With Coronary Heart Disease in Selected Obstructed Artery
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
PHASE2
Conditions: Coronary Artery Disease
Lead sponsor: Hospital y Clinica OCA, S.A. de C.V.
Sponsor class: OTHER
First posted: 2010-01-15
Enrollment: 10
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The aim of this study is to evaluate if the intracoronary infusion of autologous bone-marrow derived CD133+ endothelial precursor cells is able to promote neovascularization and to improve myocardial perfusion and contractility in patients with refractory coronary heart disease, characterized by poor response to standard coronary interventions, severe impairment of the quality of life, and poor prognosis.

Detailed description: Refractory Coronary Artery Disease is a significant cause of mortality and decreased quality of life. Intracoronary infusion of CD133+ progenitor cells is a viable treatment option for patients with this condition. After clinical and laboratory evaluation, 50-100 ml of bone marrow will be obtained by bone marrow aspiration from the posterior iliac crest under local anesthesia. From this sample, CD133+ endothelial progenitor cells will be isolated, purified and packed within the next 12 hours of extraction, and resuspended in 30 ml saline solution. The patient will undergo coronary catheterization for selection of the target obstructed artery for cell infusion, which will be performed using a balloon catheter under hemodynamic monitoring. Once concluded, the patient will be transferred to intermediate care unit for post-interventional observation for approximately 24 hours before being released. Ambulatory follow-up will be performed at specific intervals to determine efficacy and safety of this intervention by clinical and laboratory examination, including imaging and cardiac function studies.

Eligibility criteria: Inclusion Criteria:

* Patients with proven CHD by coronary angiography demonstrating occlusion or extreme stenosis (\> 90%) of a coronary artery (target artery) not suitable for angioplasty or surgery.
* Angiographic criteria: Feasibility for balloon catheter placement without risks of obstruction of the left main coronary trunk.
* Evidence of viable myocardial tissue in the area irrigated by the target artery by MRI (low dose dobutamine and late enhancement).
* CCS class 2-4 angina pectoris (angina pectoris at rest and at light exertion, obvious reduction in the exertion capacity).
* Optimal antianginal pharmacologic therapy (consistent with the current guidelines of ACC (American College of Cardiology), as well as the DGK (Deutsche Gesellschaft für Kardiologie)
* Signed written consent form accepted by the Ethics Committee.
* Effective contraception in women of child-bearing age.

Exclusion Criteria:

* Severe symptomatic heart failure (NYHA class 4).
* Myocardial aneurysm (in the target region) without evidence of viable myocardium.
* Myocardial infarction in the last 4 weeks.
* Symptomatic ventricular tachycardia.
* Known malignancy.
* Known hematological disease.
* Renal insufficiency with creatinine \> 2.5 mg/dl.
* Pregnancy.
* Active chronic inflammatory bowel disease or rheumatic disease with high parameters of inflammation (WBCs above 10/nl and increased C-reactive protein). Systemic steroid administration.
* Severe coagulopathy or phenprocoumon type anticoagulation therapy at the time of bone marrow extraction.
* Antiproliferative therapy (chemotherapy, etc.).
* Non accordance with procedures and follow-up studies.
* Contraindications to MRI studies.
* Known hypersensitivity against mouse immunoglobulins.
* Known hypersensitivity against ferridextran.
* Contraindications for bone marrow extraction.
* Cerebrovascular accident in the past four months.

Primary outcomes:
measure: Increased regional and global myocardial contractility measured by low-dose dobutamine echocardiography/MRI and increased myocardial perfusion measured by adenosine nuclear stress testing.
timeFrame: Base-line, 3, and 6 months.
Secondary outcomes:
measure: Improvement in the heart failure functional class measured by NYHA and CCS classification tests.
timeFrame: Base-line, 3, and 6 months
measure: Changes in the score of the "Minnessota living with heart failure score".
timeFrame: Base-line, 3, and 6 months.
measure: Functional heart changes measured by spiroergometry.
timeFrame: Base-line, 3, and 6 months.
measure: Reduction in the consumption of medicines for the heart ailment (nitrates, diuretics, etc.).
timeFrame: Base-line, 3, and 6 months.
measure: Safety and compatibility through evaluation of adverse events (death, supraventricular and ventricular arrhythmias, brain/peripheral ischemic events, myocardial infarct, malignancies, etc.).
timeFrame: Base-line, 3, and 6 months.
Other outcomes:
Locations:
city: Monterrey
country: Mexico
facility: Hospital y Clinica OCA, S.A de C.V.
state: Nuevo Leon
Study officials:
affiliation: Director, Cell Therapy Laboratory. OCA Hospital
name: Augusto Rojas-Martinez, M.D./D.Sc.
role: STUDY_CHAIR
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