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

Primary Purpose

Peripheral Artery Disease, Vascular Disease, Critical Limb Ischemia

Status

Completed

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

Injection of cBMA aspirate into the index leg

About this trial

This is an interventional treatment trial for Peripheral Artery Disease focused on measuring BKA, amputation, MarrowStim, below knee amputation, wound complication, vascular disease, critical limb ischemia, peripheral artery disease, AKA, stem cells, bone marrow

Eligibility Criteria

40 Years - 90 Years (Adult, Older Adult)FemaleDoes not accept healthy volunteers

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.

Sites / Locations

Indiana University School of Medicine

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Arm Label

Day 7

Day 14

Day 21

Arm Description

BKA performed at 7 days post autologous cBMA injection. 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

BKA performed at 21 days post autologous cBMA injection. Injection of cBMA aspirate into the index leg

Outcomes

Primary Outcome Measures

Number of participants with treatment-related adverse events occurring during the enrollment period as assessed by the Investigator using the CTCAE 4.0 scale.

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

Time period of retention of allogeneic MSCs in harvested human skeletal muscle tissue post-MSC implantation as measured by immunohistochemical staining and number of MSCs per section of skeletal muscle at each time point .

Sections of skeletal muscle collected from each injection site will be stained with specific antibodies for MSC specific markers and the number of MSCs will be counted in each field under a microscope.

The role of MSCs injected in human skeletal muscle at the time of below knee amputation as evidenced by recruitment of proangiogenic hematopoietic cells into sites of ischemia.

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, examine changes in morphology, and the recruitment of HIF-1a/SDF-1/CXCR4 to ischemic muscle.

Full Information

NCT ID

NCT02863926

First Posted

May 2, 2016

Last Updated

September 29, 2023

Sponsor

Michael Murphy

Collaborators

Zimmer Biomet

1. Study Identification

Unique Protocol Identification Number

NCT02863926

Brief Title

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

Acronym

MarrowCHAMP

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

2. Study Status

Record Verification Date

September 2023

Overall Recruitment Status

Completed

Study Start Date

January 6, 2017 (Actual)

Primary Completion Date

July 27, 2018 (Actual)

Study Completion Date

July 27, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor-Investigator

Name of the Sponsor

Michael Murphy

Collaborators

Zimmer Biomet

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

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

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Parallel Assignment

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.

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

6 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Day 7

Arm Type

Experimental

Arm Description

BKA performed at 7 days post autologous cBMA injection. Injection of cBMA aspirate into the index leg

Arm Title

Day 14

Arm Type

Experimental

Arm Description

BKA performed at 14 days post autologous cBMA injection. Injection of cBMA aspirate into the index leg

Arm Title

Day 21

Arm Type

Experimental

Arm Description

BKA performed at 21 days post autologous cBMA injection. Injection of cBMA aspirate into the index leg

Intervention Type

Biological

Intervention Name(s)

Injection of cBMA aspirate into the index leg

Other Intervention Name(s)

concentrated bone marrow, cBMA

Intervention Description

Injection of cBMA into the anterior tibialis muscle and upper index leg of subjects scheduled for semi-elective BKA 7-21 days before surgery

Primary Outcome Measure Information:

Title

Number of participants with treatment-related adverse events occurring during the enrollment period as assessed by the Investigator using the CTCAE 4.0 scale.

Description

Time Frame

Primary follow up in a 12 month period

Secondary Outcome Measure Information:

Title

Description

Time Frame

Primary follow up in a 12 month period

Title

The role of MSCs injected in human skeletal muscle at the time of below knee amputation as evidenced by recruitment of proangiogenic hematopoietic cells into sites of ischemia.

Description

Time Frame

Primary follow up in a 12 month period

10. Eligibility

Sex

Female

Minimum Age & Unit of Time

40 Years

Maximum Age & Unit of Time

90 Years

Accepts Healthy Volunteers

Eligibility Criteria

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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Michael P Murphy, MD

Organizational Affiliation

Indiana University

Official's Role

Principal Investigator

Facility Information:

Facility Name

Indiana University School of Medicine

City

Indianapolis

State/Province

Indiana

ZIP/Postal Code

46202

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

Yes

IPD Sharing Plan Description

De-identified data will be shared with investigators at the Indiana University School of Medicine as well as at other collaborating institutions.

IPD Sharing Time Frame

Data will become available as it is generated and will be available for future, yet-to-be-written protocols.

IPD Sharing Access Criteria

Access to de-identified data will be granted for future PI approved indications.

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

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