Cardiac Repair Cell (CRC) Treatment of Patients With Heart Failure Due to Dilated Cardiomyopathy (IMPACT-DCM)

Condition(s) targeted: Dilated Cardiomyopathy

Intervention: Cardiac Repair Cells (CRCs) (Biological)

Phase: Phase 2

Status: Recruiting

Sponsored by: Aastrom Biosciences

Official(s) and/or principal investigator(s):
Amit Patel, MD, Principal Investigator, Affiliation: University of Utah

Overall contact:
Judy Douville, Phone: 734-930-5555, Email: mail@aastrom.com

This study is designed to assess the safety and tolerability of Cardiac Repair Cells (CRCs) compared to standard-of-care in patients with dilated cardiomyopathy (DCM).

Official title: Intramyocardial Delivery of Autologous Bone Marrow Cells in Patients With Heart Failure Due to Dilated Cardiomyopathy

Study design: Treatment, Randomized, Open Label, Parallel Assignment, Safety/Efficacy Study

Primary outcome: Incidence of major adverse cardiac event (MACE) (MACE defined as: cardiac death, cardiac arrest, myocardial infarction, ventricular tachycardia, ventricular fibrillation, pulmonary edema, acute heart failure, unstable angina and major bleeding)

Secondary outcome:

Left ventricular ejection fraction (to be assessed by cine MRI/cardiac CT and Echocardiography)

Change in LV and RV dimensions and volumes as measured by MRI or cardiac CT and Echocardiography

Wall Motion Score Index (WMSI) (As determined by MRI/cardiac CT or Tissue Doppler Echocardiography. Regional wall motion at rest will be determined by cine MRI using a 17-segment model to yield the WMSI)

Regional myocardial contractility and maximal elasticity in the dysfunctional segments

Perfusion (To be assessed by Tc-SPECT in patients with IDCM only. In patients unable to perform physical exercise, adenosine will be used.)

FDG-PET (Measurements in both IDCM and non-IDCM patients performed to determine myocardial perfusion and metabolism)

Physical exercise capacity (to be determined by the change in distance covered during the 6 minute walk test)

Heart failure symptoms (to be determined by the status and changes documented by measurement of MVO2)

New York Heart Association (NYHA) and Canadian Cardiovascular Society (CCS) class (to be determined by the status and change from baseline)

Forced Expiratory Volume in 1 second (status and change as assessed by Spirometry according to ATS/ERS guidelines)

Minnesota Living with Heart Failure Score (MLHFQ)

Incidence of implantation/transplantation of implantable devices (implantable device use determined by percentage of patients undergoing ICD implantation, intraaortic balloon pump implantation, Cardiac Assist Device implantation or heart transplantation)

Heart failure markers (as determined by absolute concentrations and changes to the heart failure markers Troponin I and BNP measured in the peripheral blood)

Heart failure medications (e.g. beta-blockers, ACE inhibitors, Digoxin, Diuretics, Vasodilators, Anti-arrhythmic drugs, and Nitroglycerine)

Assessment of aspiration site throughout study

Acute post-surgical monitoring of vital signs, special labs and markers, and ECHO

Assessment of incision site for month following surgery

Standard chemistry panel including kidney and liver function tests, complete blood count and physical exam, as well as monitoring of vital signs

Special labs associated with heart function throughout the study, as well as x-ray at 3 mos to evaluate congestion

Specialized cardiac testing to monitor heart function, i.e., ECG, Holter monitor, ECHO, MRI/CT, SPECT, PET testing

Adverse Event monitoring as well as monitoring specifically for MACE

Detailed description: Heart failure remains a major public health problem, affecting 5 million patients in the US with 550,000 new diagnoses made each year. Heart failure is the leading cause of hospitalization in persons over 65 years of age with cost exceeding $29 billion annually. Prognosis is very poor once a patient has been hospitalized with heart failure. The mortality risk after heart failure hospitalization is 11. 3% at 30 days, 33. 1% at 1 year and well over 50% within 5 years (Hunt SA; et al., 2005). These numbers emphasize the need to develop and implement more effective treatments to manage heart failure.

This study is targeting a subset of heart failure patient population, namely those diagnosed with dilated cardiomyopathy (DCM). The World Health Organization (WHO) defines dilated cardiomyopathy as a cardiac condition wherein a ventricular chamber exhibits increased diastolic and systolic volume and a low (<40%) ejection fraction. DCM is reported to affect 108,000 to 150,000 patients in the U. S.

This study is a prospective, stratified, randomized, open-label, controlled, multi-center study to assess the safety profile and efficacy of CRCs in treating patients with DCM. It will enroll a total of 40 patients at 5 sites in the U. S.

Minimum age: 18 Years. Maximum age: 86 Years. Gender(s): Both.

Criteria:

Inclusion Criteria:

- Diagnosis of ischemic or nonischemic DCM according to World Health Organization

criteria; OR ischemic DCM (DCM in a patient with a history of myocardial infarction or evidence of clinically significant (>/= 70% narrowing of a major epicardial artery) coronary artery disease)

- No other cardiac surgery or percutaneous cardiac interventions likely to produce

clinical improvement, in the opinion of the investigator and the referring interventional cardiologist

- Left ventricular ejection fraction

- Symptomatic heart failure in NYHA functional class III or IV

- Able to comply with scheduled visits in cardiac out-patient clinic

- Able to tolerate study procedures, including bone marrow aspiration, left lateral

thoracotomy or thoracoscopy with single lung ventilation, MRI or cardiac CT, spirometry and 6 minute walk test

- Males and females, 18-86 years of age

- Life expectancy of 6 months or more in the opinion of investigator

- Able to give informed consent

- Normal organ and marrow function (Leukocytes >/= 3,000/microgram, Absolute neutrophil

count >/= 1,500/microgram, Platelets >/= 140,000/microgram, AST (SGOT)/ALT (SGPT) - Adequate pulmonary function (forced expiratory volume in one second [FEV1] > 50%

predicted)

- Controlled blood pressure (systolic blood pressure - Adequate medical management of DCM and other pre-existing conditions. Drug treatment

regimen must have been established for at least a month prior to randomization in eligible patients.

- Fertile patients must agree to use an appropriate form of contraception while

participating in the study

Exclusion Criteria:

- Severe primary valvular insufficiency(ies)

- Known history of Chronic Obtrusive Pulmonary Disease (Gold stages IIB or more severe

only) or restrictive pulmonary disease

- Known history of primary pulmonary hypertension

- Ventricular Assist Device implantation

- Myocardial infarction within 4 weeks of randomization

- Life-threatening ventricular arrhythmia, except if implantable cardioverter

defibrillator is implanted

- Unstable angina, characterized by increasingly frequent episodes with modest exertion

or at rest, worsening severity, and prolonged duration

- Patients receiving treatment with hematopoietic growth factors

- Patients who require uninterruptible anticoagulation or anti-platelet therapy [i. e.

anticoagulation therapy (e. g. warfarin) that cannot be stopped for 72 hours prior to bone marrow aspiration and intramyocardial injections]

- Patients receiving anti-platelet therapy (e. g. clopidogrel) that cannot be stopped

for 7 days prior to bone marrow aspiration and intramyocardial injections

- Known cancer and undergoing treatment including chemotherapy and radiotherapy

- Patients who will require continuous, systemic, high dose corticosteroid therapy

(more than 7. 5 mg/day) within 6 months after surgery

- End stage renal disease requiring dialysis

- Patients pregnant or lactating; positive for hCG

- History of alcohol consumption regularly exceeding the equivalent of 2 drinks/day (1

drink = 5 oz of wine or 12 oz [360mL] of beer or 1. 5 oz [45mL] of hard liquor) or history of illicit drug use within 6 months of screening

- Known allergies to protein products (horse or bovine serum, or porcine trypsin)

- Body Mass Index of 40 Kg/m2 or greater

- Patients receiving experimental medications or participating in another clinical

study within 30 days of screening

- HIV or syphilis, positive at time of screening

- Active Hepatitis B, or Hepatitis C infection at time of screening

- In the opinion of the investigator, patient is unsuitable for cellular therapy

- Patients receiving anti-angiogenic drugs

Judy Douville, Phone: 734-930-5555, Email: mail@aastrom.com

Emory University Hospital Midtown, Atlanta, Georgia 30308, United States; Recruiting
Shannon Smith, RN, Phone: 404-686-3373, Email: shannon.smith@emoryhealthcare.org
Omar Lattouf, MD, PhD, Principal Investigator

Cleveland Clinic Heart and Vascular Institute, Cleveland, Ohio 44195, United States; Recruiting
Linda Clarke, RN, Phone: 216-445-6567, Email: CLARKEL@ccf.org
Nicholas Smedira, MD, Principal Investigator

Methodist DeBakey Heart & Vascular Center, Houston, Texas 77030, United States; Recruiting
Raquel Bunge, RN, Phone: 713-441-5357, Email: Rrbunge2@tmhs.org
Brian Bruckner, MD, Principal Investigator

Baylor University Medical Center, Dallas, Texas 75226, United States; Recruiting
Poupak Moshayedi, Phone: 214-820-2273, Email: Poupak.moshayedi@baylorhealth.edu
Baron Hamman, MD, Principal Investigator

The University of Utah School of Medicine, Salt Lake City, Utah 84132, United States; Recruiting
Patty Meldrum, Phone: 801-581-4121, Email: Patty.meldrum@hsc.utah.edu
David Bull, MD, Principal Investigator

Starting date: September 2008
Ending date: June 2010
Last updated: August 10, 2009