Clinical Research Details

Use of TRC Autologous Bone Marrow Cells in Patients with Peripheral Arterial Disease to Treat Critical Limb Ischemia

The purpose of this clinical research is to determine if bone marrow cells that are harvested from a patient's bone and expanded can be used as a method for treatment of critical limb ischemia in patients with peripheral artery disease.

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Adults, 18-90 years of age, with a diagnosis of chronic critical limb ischemia defined as persistent, recurring ischemic rest pain for at least 2 weeks, and/or ulceration or gangrene of the foot or toe, with toe systolic pressure< 50 mmHg (or absent palpable pedal pulse in patients with diabetes) or ankle systolic pressure < 70 mmHg (TASC).
Patients with infra-inguinal occlusive disease, but without acceptable options for revascularization, may also be eligible. This has to be confirmed by angiographic imaging results or by color flow duplex ultrasound obtained within the last 6 months prior to randomization.

There must be no endovascular intervention or surgical revascularization in the target limb are anticipated within 3 months post-randomization. Potential participants must have normal organ and marrow function as defined: Leukocytes ³3,000/mL, Absolute neutrophil count ³1,500/mL, Platelets ³140,000/mL, AST (SGOT)/ALT (SGPT) =2.5 X institutional standards range. Patients must have controlled blood pressure (defined as a systolic blood pressure =180 and a diastolic blood pressure of <110 mmHg) and established anti-hypertensive therapy as necessary prior to randomization.
Potential participants must have adequate anti-platelet therapy (acetyl salicylic acid > 81 mg/day or clopidogrel > 75 mg/day) established prior to randomization.

All patients with CLI due to atherosclerosis are required to receive statin therapy unless contraindicated. Exclusion criteria;
1. Patients with poorly controlled diabetes mellitus (HbA1c > 10.0%). 2. Patients with aortoiliac disease with > 50% stenosis.
3. Wounds with a severity greater than Grade 3 on the Wagner Scale. 4. Patients with a known failed ipsilateral revascularization procedure within 2 weeks prior to randomization. A failed revascularization procedure is defined as any procedure that has failed to restore adequate circulation (defined as a change in ABI of .15 or more or substantial improvement in PVR or clinical improvement).
5. Patients with previous amputation of the talus, or above in the target limb.

6. Any patient with a life-threatening ventricular arrhythmia - except if an AICD is implanted - or unstable angina - characterized by increasingly frequent episodes with modest exertion or at rest, worsening severity, and prolonged duration, or myocardial infarction within 4 weeks prior to randomization.

7. Patient with severe congestive heart failure (i.e. NYHA Stage IV).

8. Patients receiving treatment with hematopoietic growth factors (e.g. erythropoietin, G-CSF). Erythropoietin treatment in ESRD patients is allowed.

9. Infection of the involved extremity(ies) manifest by fever, purulence and severe cellullites.

10. Active wet gangrenous tissue.
11. Patients who require uninterruptible anticoagulation therapy or anti-platelet therapy [j.e. anticoagulation therapy (e.g. warfarin) that cannot be stopped for 72 hours prior to bone marrow aspiration and intramuscular injections, except those who are eligible for bridge anticoagulation therapy with low molecular weight heparin which can be interrupted for 12 hours]. In addition, all patients receiving anti-platelet therapy (e.g. clopidogrel) that cannot be stopped for 7 days prior to bone marrow aspiration are excluded. 12. Patients with a blood clotting disorder not caused by medication.

13. Patients with known cancer undergoing treatment including chemotherapy, radiotherapy or immunotherapy. 14. Patients with end stage renal disease and undergoing renal dialysis for more than 6 months prior to randomization. 15. Patients who are pregnant or lactating; positive for hCG.

16. History of regular alcohol consumption exceeding 2 drinks/day (1 drink = 5 oz [150 ml] of wine or 12 oz [360mL] of beer or 1.5 oz [45mL] of hard liquor) within 6 months of screening and/or history if illicit drug use.

17. Known allergies to protein products (horse or bovine serum or porcine trypsin) used in the ex-vivo cell production process.

18. Patients current Body Mass Index (BMI) is 40 Kg/m2 or greater.

19. Patients receiving experimental medications or participating in another clinical study (e.g., a Phase IV study) within 30 days of screening.

20. HIV, syphilis, positive at time of screening.

21. Active Hepatitis B, or Hepatitis C infection at the time of screening.

22. Patients having received medication for thrombolytic therapy (e.g. rTPA or other enzymatic clot busters) with in 30 days prior to randomization.
randomization.

23. Patients undergoing hyperbaric oxygen treatment within 4 weeks of inclusion and/or required throughout the trial.

24. Concomitant wound treatments that include growth factors or tissue engineered products, except for patients on chronic Becaplermin (topical), in which case, use of Becaplermin would have to cease prior to study injections and for the duration of the study.
25. In the opinion of the investigator, the patient is unsuitable for cellular therapy.26. Patients receiving systemic or direct target limb injection of anti-angiogenic drugs. (e.g., anti-VEGF).

One group of patients will be treated with an experimental tissue product that is produced from a small amount of their own bone marrow. The bone marrow from the hip and injected into the leg that is affected with critical limb ischemia. The other group (the control group) will undergo a mock bone marrow collection and be treated with an electrolyte solution (isotonic salt solution) injected into their affected leg. If you are part of the control group (the group receiving the isotonic salt solution), you will not receive the experimental tissue product.

Patrick Stiff, M.D.

(708) 216-2026