Use of Autologous Concentrated Bone Marrow Aspirate in Preventing Wound Complications in Below Knee Amputation (BKA)

Phase 1

Completed

Conditions: Vascular Disease
Peripheral Artery Disease
Critical Limb Ischemia

Brief Summary: Patients scheduled for major extremity lower amputation to receive bone marrow cells (cBMA) injected IM in the leg proximal to the amputation in the index limb to prevent ischemic wound complications after surgery.

Detailed Description: Patients scheduled for amputation will receive bone marrow cells concentrated via the MarrowStim device (cBMA) injected IM at 25 sites in the leg proximal to the amputation in the index limb to prevent ischemic wound complications after surgery. cBMA will be injected into the anterior tibialis muscle below the point of amputation in an area approximately 3cm\^2 x 2cm\^2 for analytical purposes. Patients will be scheduled for amputation at Days 7, 14, or 21 post injection. Safety will be evaluated by review of treatment related adverse events (AE) during the 52-week follow-up period. The investigator will compare rates of wound complications and amputation revisions to historical controls at the institution to assess trends in therapeutic efficacy.

Patients will undergo amputation and injection sites will be harvested at that time. Immunohistochemical staining (IHC) will determine capillary density and local host immune responses. Angiogenic and inflammatory cytokines will be quantified using a multiplex array system and quantitative polymerase chain reaction (PCR).

Recruitment & Eligibility

Inclusion Criteria

Be ≥ 40 and ≤90 years of age.
Patients requiring below knee amputation, as determined by an independent vascular specialist.
If ulceration or gangrene present, it is distal to malleoli (to allow adequate length of ATM for 4 injections 4 cm. apart)
BKA can safely be performed up to 30 days after screening, as determined by an independent vascular or orthopedic surgeon. This information will be documented in subjects' case report forms (CRFs).
Females of childbearing potential must be willing to use one form of birth control for the duration of the study. Female participants must undergo a blood or urine pregnancy test at screening.

Exclusion Criteria

Patients who are pregnant, planning to become pregnant in the next 12 months, or lactating.
Significant hepatic dysfunction (ALT or AST greater than 2 times normal).
CHF hospitalization within the last 1 month prior to enrollment.*
Acute coronary syndrome (ACS) in the last 1 month prior to enrollment.*
HIV positive, or active, untreated HCV.
History of cancer within the last 5 years, except basal cell skin carcinoma
Any bleeding diathesis defined as an INR ≥ 2.0 (off anticoagulation therapy) or history of platelet count less than 70,000 or hemophilia.
Inability to provide written informed consent due to cognitive or language barriers (interpreter permitted).
Concurrent enrollment in another clinical investigative trial.
Any condition requiring immunosuppressant medications (e.g., for treatment of organ transplants, psoriasis, Crohn's disease, alopecia areata).
Presence of any clinical condition that in the opinion of the PI or the sponsor makes the patient not suitable to participate in the trial.
- As defined by the standard definitions of CHF and ACS by the American Heart Association.

Arm && Interventions

Group	Intervention	Description
Day 7	Injection of cBMA aspirate into the index leg	BKA performed at 7 days post autologous cBMA injection. Injection of cBMA aspirate into the index leg
Day 14	Injection of cBMA aspirate into the index leg	BKA performed at 14 days post autologous cBMA injection. Injection of cBMA aspirate into the index leg
Day 21	Injection of cBMA aspirate into the index leg	BKA performed at 21 days post autologous cBMA injection. Injection of cBMA aspirate into the index leg

Primary Outcome Measures

Name	Time	Method
Number of Participants With Treatment-related Adverse Events Occurring During the Enrollment Period as Assessed by the Investigator Using the CTCAE 4.0 Scale.	12 months	Safety will be evaluated by review of treatment related AEs during the 12-month follow-up period. The study will be terminated in the event of a Grade 4-5 unexpected event based on the Common Terminology Criteria for Adverse Events (CTCAE), version 4.0. Treatment-related AEs will be categorized overlapping systems and severities. Three categories of systems are cardiovascular, respiratory, or infectious. Two categories of severity will be serious adverse (SAE) and major adverse cardiac events (MACE). Binomial confidence Intervals at the 95% confidence level and p-values for these 3 groups will be calculated. Since previous trials have not reported AEs with cBMA treatment, confidence intervals will be generated by the method of the Wilson Score Interval.

Secondary Outcome Measures

Name	Time	Method
Number of Participants With Conversion From Below Knee Amputation to Above Knee Amputation as Evidenced by Wound Complications at the Below Knee Amputation Stump Site.	12 months	Documentation will be collected on wound complications at the below knee amputation surgical site resulting in necessity of revision/conversion to above knee amputation.
The Role of Autologous Bone Marrow Cells Injected in Human Skeletal Muscle in Inducing Capillary Vessel Formation at the Time of Below Knee Amputation.	12 months	Continuous confidence intervals at the 95% level will be constructed to explore differences among the time-tiered administration of MSC for the quantity of capillary density in muscle fibers.