Proteomics and Stem Cell Therapy as a New Vascularization Strategy

• Status: Unknown status
• Trial end date: 2017-03-01
• Target enrollment: 0
• Participant gender: All

Summary

Neovascularization (NV) is the innate capability to enlarge collateral arteries ("arteriogenesis"), and to stimulate growth of new capillaries, arterioles and venules at the tissue level ("angiogenesis"). Patients with Chronic Limb-threatening Ischemia (CLI) present with forefoot rest-pain, ulceration and/or gangrene. They require risky and costly revascularization operations to avoid amputation. The investigators hypothesize that their inadequate NV can be modulated to restore this capability. By correcting impediments to NV in an out-patient setting, the investigators expect to facilitate CLI management.

While the following impediments to NV are complex, the solution is not. Arteriogenesis necessitates endothelial cell activation in small collaterals as blood is offloaded away from the occluded artery. Shear stress provides this stimulus, but is attenuated caudal to multi-level arterial occlusive disease. The "arteriogenesis switch" is not turned on. Furthermore, the lack of nutritive oxygenated blood inflow and the accumulation of toxic metabolic by-products are adverse to synthetic pathways in the ischemic tissue. Additionally, protein "distress" signals cannot be effectively disseminated by the ischemic tissue, and the reparative progenitor cells they are supposed to mobilize cannot effectively home back to the ischemic tissue to orchestrate NV. The CLI patient is especially disadvantaged by having diminished function and number of circulating progenitor cells (CPC). Lastly these elderly, often diabetic, patients are less able to fend off infection.

An FDA approved external programmed pneumatic compression device (PPCD) was used to restore the shear stress stimulus required for arteriogenesis. It also enhances oxygenated nutritive arterial inflow, clears waste products of metabolism (increased venous and lymphatic outflow), and helps distress proteins reach the central circulation and mobilized progenitor cells to return to the ischemic tissue. We corrected the progenitor cell and immunologic impairment with granulocyte colony stimulating factor (G-CSF), FDA approved for stem cell mobilization and immunological boost in the setting of cancer chemotherapy. The preliminary data show clinical, angiographic, hemodynamic and biochemical evidence for enhanced NV. The purpose for this study is to enroll 25 patients to reproduce the biochemical data to support a large scale clinical trial.

• Phase: N/A
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University of Illinois at Chicago
• Treatments: Lenograstim

Criteria

Inclusion Criteria:

1. Male or female between the ages of 35 and 85.

2. Chronic limb ischemia Fontaine Class III (ischemic forefoot rest pain) and Class IV (non-healing ischemic ulcers, gangrene) with confirmatory non-invasive vascular testing.

3. English or Spanish speaking patients

Exclusion Criteria:

1. Acute limb ischemia requiring emergency treatment.

2. Non-salvageable foot (e.g. extensive gangrene, advanced infection, rigor mortis, knee/hip flexion contracture, post-stroke paralysis, and hemiparesis).

3. Untreated hypercoagulability disorder, sickle cell anemia, myeloproliferative disorder.

4. Dialysis, and/or sustained elevated Creatinine >3.6 mg/dl.

5. Severe dementia; bed-ridden; non-compliance; unlikely to follow-up; unreliable.

6. Intolerance of PPCD compression

7. Morbid obesity (Body Mass Index > 34)

8. Severe venous insufficiency causing venous stasis ulceration and dermatitis.

9. Uncorrected significant aorto-iliac, common femoral, and profunda femoral arterial disease

10. Ulceration precluding PPCD placement.

11. Active cancer.

12. Allergy to Neupogen.

13. Uncorrected symptomatic coronary artery disease

14. History of lymphoma or leukemia