Use of Adult Autologous Stem Cells in Treating People 2 to 3 Weeks After Having a Heart Attack (The Late TIME Study)

Heart attacks are a leading cause of death for both men and women in the United States. A
heart attack occurs when blood flow to the heart is restricted, commonly due to a blood clot
that has formed in one of the coronary arteries. If the clot becomes large enough, blood
flow to the heart can be blocked almost completely and the heart muscle in that area can
suffer permanent injury or death. Although a PCI can be used to open up the blocked artery
and restore blood flow to the heart muscle, there may be a significant amount of heart
tissue that has been irreversibly damaged. Recent studies have shown that adult stem cells
from bone marrow may be able to improve heart function after a heart attack. These
specialized cells may have the ability to promote blood vessel growth, prevent cell death,
and transform themselves into a number of tissues, including muscle. After an acute heart
attack, a remodeling process is initiated in the heart in an attempt to compensate for
damaged areas. Consequently, the condition of the heart muscle several weeks after a heart
attack may differ considerably from the heart's condition during the acute setting. For some
patients, delaying the delivery of the stem cells until 2 to 3 weeks after a heart attack
may be better than initiating treatment during the acute phase. This study will evaluate the
safety and effectiveness of placing adult stem cells into injured heart muscle 2 to 3 weeks
after a heart attack for improving heart function in people who have had a recent heart
attack and a PCI.

Participation in this study will last 24 months. All participants will first undergo
baseline assessments that will include a medical history, a physical exam, an
electrocardiogram (ECG), blood draws, an echocardiogram, and a magnetic resonance imaging
(MRI) test. Participants will then be assigned randomly to receive stem cells or placebo
between 2 and 3 weeks after their heart attack. The morning of the stem cell or placebo
infusion, participants will undergo a blood draw and a bone marrow aspiration procedure of
the hip bone to collect the stem cells. Later the same day, either stem cells or placebo
will be infused through a catheter and into the damaged area of the heart.

For the first 24 hours after the infusion, participants will be asked to wear a small ECG
machine called a Holter monitor. Participants will also be asked to record their temperature
twice a day for a month after the infusion. Participants will return for follow-up visits at
Months 1, 3, 6, 12, and 24 and will repeat many of the baseline assessments.

Inclusion criteria

1. Patients at least 21 years of age.

2. Patients with first acute MI and subsequent successful primary percutaneous coronary
intervention (PCI) in an artery at least 2.5 mm in diameter occurring two to three
weeks before recruitment.

3. No contraindications to undergoing cell therapy procedure within two to three weeks
following AMI and PCI.

4. Hemodynamic stability as defined as no requirement for IABP, inotropic or blood
pressure supporting medications.

5. Ejection fraction following reperfusion with PCI <=45% as assessed by
echocardiography.

6. Consent to protocol and agree to comply with all follow-up visits and studies.

7. Women of child bearing potential willing to use an active form of birth control.

Exclusion criteria

Patients will be excluded from the study if they meet any of the following conditions:

1. History of sustained ventricular arrhythmias not related to their AMI (evidenced by
previous holter monitoring and/or medication history for sustained ventricular
arrhythmias in patient's medical chart).

2. Require CABG or PCI due to the presence of residual coronary stenosis >70% luminal
obstruction in the non-infarct related vessel (Additional PCI of non-culprit vessels
may be performed prior to enrollment).

3. History of any malignancy within the past five years excluding non-melanoma skin
cancer or cervical cancer in-situ.

4. History of chronic anemia (hemoglobin (Hb) <9.0 mg/dl).

5. History of thrombocytosis (platelets >500k).

6. History of thrombocytopenia in the absence of recent evidence that platelet counts
are normal

7. Known history of elevated INR (PT) or PTT.

8. Life expectancy less than one year.

9. History of untreated alcohol or drug abuse.

10. Currently enrolled in another Investigational drug or device trial

11. Previous CABG.

12. Previous MI resulting in LV dysfunction (LVEF <55%)

13. History of stroke or transient ischemic attack (TIA) within the past six months.

14. History of severe valvular heart disease (aortic valve area <1.0 cm2 or >3+ mitral
regurgitation).

15. Pregnancy or breast feeding

16. Subjects with a known history of HIV, or has active hepatitis B, active hepatitis C,
or active tuberculosis (TB)

17. Patients with active inflammatory or autoimmune disease on chronic immunosuppressive
therapy.

18. Contraindications to cMRI.

19. Previous radiation to the pelvis with white blood cell count (WBC) and platelet
counts below hospital specific normal values.

20. Women child bearing potential not willing to practice an active form of birth
control.

21. Chronic liver disease that might interfere with survival or treatment with cell
therapy.

22. Chronic renal insufficiency as defined by a creatinine ≥2.0 mg/dL or requires chronic
dialysis.