Critical Limb Ischemia
Conditions
Keywords
Cord blood injection in peripheral vascular disease
Brief summary
The purpose of this study is to determine whether treatment with umbilical cord blood stem cells will improve blood flow to the most severely affected leg of a participant with medically refractory and non-surgical peripheral vascular disease of the lower extremity.
Detailed description
Umbilical cord blood is a safe alternative source of stem cells used for decades in hematopoietic stem cell transplants for malignancies. There is also a reported decreased incidence of acute GVHD compared to matched unrelated donor transplants.A cord blood registry will be searched for suitable units with compatibility in the ABO and HLA systems. The minimum total nucleated cell dose required which would be 1.0 x 107/kg, and one unit of cells will be procured to meet this requirement. Although it is likely that the transplanted cord blood cells will be rejected over time, we hypothesize that while they remain in the host's tissue these cells will be producing and releasing cytokines, growth factors and other humoral factors that might promote vasculogenesis by stimulating endogenous stem cells and endothelial cells. Since there is no need to collect the patient's own stem cells, the patient's cardiovascular system will not be subjected to any stress due to the leukapheresis procedure itself. No injections of exogenous growth factors, which have been associated with thrombosis, would be required to mobilize the patient's own stem cells. The procedure could conceivably even be performed in its entirety on an outpatient basis. A total of 25 patients will be enrolled in the study. Patients will be followed for 24 months after the procedure with evaluation visits one day after the transplant and then at one month, six, twelve and twenty four months post-treatment. The visit one day after the transplant will involve a history and physical with a leg exam, a CBC and a chemistry panel to evaluate for possible infection, or other adverse event.
Interventions
BIOLOGICALCord blood stem cell injection
The cord blood stem cells will be simply injected intramuscularly in the leg. 30 minutes prior to stem cell injection the patients will receive Vancomycin 1 gram IVPB x1 as a prophylactic measure. Patients will also receive Ativan 0.5 to 1 mg PO x 1 and Dilaudid 0.5 to 1 mg IV x1 to alleviate the discomfort of the procedure. Cells will be injected by means of a 22 gauge sterile spinal needle after topical anesthesia of the injection site. The concentration will be at least 2 x 107 total nucleated cells per ml in phosphate buffered saline (PBS) with 5% human serum albumin (Baxter, Deerfield Illinois).
Sponsors
Richard Burt, MD
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 72 Years
Healthy volunteers
No
Inclusion criteria
* Atherosclerotic ischemic peripheral vascular disease or Thromboangiitis Obliterans with Critical Limb Ischemia (Fontaine stages III and IV) * Participant must match either a or b 1. Ankle brachial index (ABI) ≤ 0.7 2. Doppler waveforms at posterior tibial artery and dorsalis pedis artery are monophasic with toe pressure \< 30 mmHg. * A non-surgical candidate for revascularization e.g. prior vascular reconstruction, inability to locate a suitable vein for grafting, diffuse multi- segment disease, or extensive infra-popliteal disease not amenable to a vascular graft. * Age \> 18 years old. * The non-index leg may be treated only in the event and it full fills the same eligibility criteria and
Exclusion criteria
used in this protocol for the treatment leg. * Patients must be on maximal tolerated medical therapy for PVD including A) Cessation of smoking B) Referral to endocrinologist for control of HgA1c to \< 7.0 mg/dl, control of hyperlipidemia with statins or other anti-hyperlipidemic drugs as indicated, control of hypertension as indicated C) Antiplatelet therapy with aspirin and / or cilostazol (unless medically contraindicated, e.g. bleeding or allergy)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Ankle brachial index (ABI), a 15% increase will be considered improvement | Pre-transplant, 1, 6, 12 and 24 months after |
| Healing of ischemic ulcers | Pre-transplant, 1, 6, 12 and 24 months after |
| Decreased pain level as reported by the patient | Pre-transplant, 1, 6, 12 and 24 months after |
Secondary
| Measure | Time frame |
|---|---|
| SF-36 quality of life (QOL) | Pre-transplant, 1, 6 , 12, and 24 months after HSC transplant |
| Increase in four meter walk or six minute walk by more than 25% | Pre-transplant, 1, 6 , 12, and 24 months after HSC transplant |
| Walking Impairment Questionnaire | Pre-transplant, 1, 6 , 12, and 24 months after HSC transplant |
| Increase in pain free ambulation time on treadmill by more than 25% | Pre-transplant, 1, 6 , 12, and 24 months after HSC transplant |
Countries
United States
Outcome results
None listed