Clinical trial NCT00203203: Autologous Stem Cells for Cardiac Angiogenesis (FOCUS HF)
Official title: Randomized Controlled Single Blind Trial of Autologous Bone Marrow Mononuclear Cells Under Electromechanical Guidance for Therapeutic Angiogenesis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Ischemic Cardiomyopathy
Keywords: Autologous
Cardiac
Stem Cell
Transplant
Lead sponsor: Texas Heart Institute
Sponsor class: OTHER
Collaborators: name: CHI St. Luke's Health, Texas
First posted: 2005-09-20
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: This is a phase 1, single-blind trial to evaluate using autologous bone marrow mononuclear stem cells in ischemic cardiomyopathy patients. The patients must have a Left Ventricular Ejection Fraction (LVEF) of less than or equal to 45%. Once the patient meets all inclusion criteria, and no exclusion criteria are found, the subject is consented for the study, and extensive baseline testing is performed at St Luke's Hospital in Houston. Once all baseline testing criteria is met, the patient has their own bone marrow harvested and later that day the subject is taken to a cardiac catheterization lab where left ventricular electromechanical mapping using NOGA software (NOGA mapping) is performed and the processed stem cells are injected under electromechanical guidance into the affected areas of the left ventricle. The patient is usually discharged home the next day and returns for follow up visits at weeks 1, 2, 4, 6, 8, 12, months 6 and 12 and for phone call follow-up at months 4, 5, 7, 8, 9, 10, 11. Patients undergo extensive testing at most of these follow-up visits, including repeat cardiac catheterization with NOGA mapping at month 6 after stem cell injection.

Detailed description: This is a phase 1, single-blind trial to evaluate the use of autologous bone marrow mononuclear stem cells in ischemic cardiomyopathy patients. The study hypothesis is that transendocardial injections of autologous mononuclear bone marrow cells in patients with end-stage ischemic heart disease is safe, can promote neovascularization, and can improve perfusion and myocardial contractility. The primary object of this study will be to evaluate the safety of autologous-bone-marrow mononuclear cell injections. The secondary endpoint of the study is to assess the efficacy of autologous bone marrow cells in improving cardiac contractile function and functional outcome. The efficacy will be assessed on the basis of the treadmill Max VO2 (maximum volume oxygen uptake). Secondarily the efficacy will be assessed on the basis of clinical status and imaging rests, with follow-up extending to 1 year after enrollment.A maximum of 30 patients will be enrolled in the study. At the end of the 6-month visit. after the required angiogram with mapping and non-invasive testing is complete, the patients will be told whether they were in the control or the active group (stem cell therapy). Those in the control group will be told before final invasive testing, and those who consent may cross over to the active therapy arm and undergo the cell injection procedure (control, then stem cell therapy. In these patients, the foll-up angiogram and mapping procedure will also serve as the baseline procedure required for cell injection. Bone marrow mononuclear cells will be injected in an identical fashion, according to the same criteria described for the original treatment group, and these patients will have identical follow-up visits starting again at the baseline time-point and extending for up to 1 year.

Eligibility criteria: Inclusion Criteria:

* LVEF less than 45%
* Functional class III or IV angina
* At least 7% reversibility by Single Photon Emission Computed Tomography (SPECT) nuclear study
* there are additional inc. criteria

Exclusion Criteria:

* AGe \<18 or \>70 years of age
* Constant atrial fibrillation
* Left ventricular (LV) thrombus
* History of malignancy in the last 5 years
* LV wall thickness of \< 8 mm at the target site
* there are additional exclusion criteria

Primary outcomes:
measure: Safety of Autologous-bone-marrow Injections
timeFrame: up to 2 weeks post-procedure, 3 months and 6 months
Secondary outcomes:
measure: Canadian Cardiovascular (CCS) Angina Score
timeFrame: baseline, 3 months and 6 months
measure: New York Heart Association (NYHA)Classification
timeFrame: baseline, 3 months and 6 months
measure: Myocardial Oxygen Consumption (MVO2)
timeFrame: baseline, 3 months and 6 months
measure: Echocardiography (EF)Percent (%)
timeFrame: baseline, 3 months and 6 months
measure: Minute Ventilation- Carbon Dioxide Production Relationship (VE/VCO2 Slope)
timeFrame: baseline and 3 months
measure: Echocardiography Wall Motion Score Index (WMSI)
timeFrame: baseline and 3 months
measure: Single-photon Emission Computed Tomography (SPECT) Imaging for Left Ventricular Ejection Fraction (LVEF) Percentage (%)
timeFrame: baseline, 3 months and 6 months
measure: Angiography Left Ventricular Ejection Fraction (LVEF) Percent (%)
timeFrame: baseline and 6 months
measure: Left Ventricular End-Diastolic Volume (LVEDV)
timeFrame: baseline, 3 months and 6 months
measure: Left Ventricular End-Systolic Volume (LVESV) (ml)
timeFrame: baseline, 3 months and 6 months
measure: Endocardial Unipolar Voltages (UPV)
timeFrame: baseline and 6 months
measure: Linear Local Shortening (LLS)
timeFrame: baseline and 6 months
Other outcomes:
Locations:
city: Houston
country: United States
facility: Texas Heart Institute/Baylor St. Luke's Medical Center
state: Texas
Study officials:
affiliation: Texas Heart Institute/Baylor St Luke's Medical Center
name: Emerson Perin, MD,PhD.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Perin EC, Silva GV, Henry TD, Cabreira-Hansen MG, Moore WH, Coulter SA, Herlihy JP, Fernandes MR, Cheong BY, Flamm SD, Traverse JH, Zheng Y, Smith D, Shaw S, Westbrook L, Olson R, Patel D, Gahremanpour A, Canales J, Vaughn WK, Willerson JT. A randomized study of transendocardial injection of autologous bone marrow mononuclear cells and cell function analysis in ischemic heart failure (FOCUS-HF). Am Heart J. 2011 Jun;161(6):1078-87.e3. doi: 10.1016/j.ahj.2011.01.028. Epub 2011 May 10.