Clinical trial NCT02863926: Use of Autologous Concentrated Bone Marrow Aspirate in Preventing Wound Complications in Below Knee Amputation (BKA)
Official title: Safety and Efficacy of Concentrated Autologous Concentrated Bone Marrow Aspirate (cBMA) in Preventing Wound Complications in Below Knee Amputation (BKA) (The MarrowCHAMP Study)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Peripheral Artery Disease
Vascular Disease
Critical Limb Ischemia
Keywords: BKA
amputation
MarrowStim
below knee amputation
wound complication
vascular disease
critical limb ischemia
peripheral artery disease
AKA
stem cells
bone marrow
Lead sponsor: Indiana University
Sponsor class: OTHER
Collaborators: name: Zimmer Biomet
First posted: 2016-08-11
Enrollment: 6
Sex: ALL
Minimum age (years): 40
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Autologous bone marrow derived mesenchymal stromal cells will be delivered intramuscularly in the lower extremity of participants undergoing lower extremity major amputation to assess incidence of wound healing and infection prevention.
Primary purpose: TREATMENT

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).

Eligibility criteria: Inclusion Criteria:

1. Be ≥ 40 and ≤90 years of age.
2. Patients requiring below knee amputation, as determined by an independent vascular specialist.
3. If ulceration or gangrene present, it is distal to malleoli (to allow adequate length of ATM for 4 injections 4 cm. apart)
4. 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).
5. 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:

1. Patients who are pregnant, planning to become pregnant in the next 12 months, or lactating.
2. Significant hepatic dysfunction (ALT or AST greater than 2 times normal).
3. CHF hospitalization within the last 1 month prior to enrollment.\*
4. Acute coronary syndrome (ACS) in the last 1 month prior to enrollment.\*
5. HIV positive, or active, untreated HCV.
6. History of cancer within the last 5 years, except basal cell skin carcinoma
7. Any bleeding diathesis defined as an INR ≥ 2.0 (off anticoagulation therapy) or history of platelet count less than 70,000 or hemophilia.
8. Inability to provide written informed consent due to cognitive or language barriers (interpreter permitted).
9. Concurrent enrollment in another clinical investigative trial.
10. Any condition requiring immunosuppressant medications (e.g., for treatment of organ transplants, psoriasis, Crohn's disease, alopecia areata).
11. 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.

Primary outcomes:
measure: Number of Participants With Treatment-related Adverse Events Occurring During the Enrollment Period as Assessed by the Investigator Using the CTCAE 4.0 Scale.
timeFrame: 12 months
Secondary outcomes:
measure: 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.
timeFrame: 12 months
measure: The Role of Autologous Bone Marrow Cells Injected in Human Skeletal Muscle in Inducing Capillary Vessel Formation at the Time of Below Knee Amputation.
timeFrame: 12 months
Other outcomes:
Locations:
city: Indianapolis
country: United States
facility: Indiana University School of Medicine
state: Indiana
Study officials:
affiliation: Indiana University
name: Michael P Murphy, MD
role: PRINCIPAL_INVESTIGATOR
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