Enhanced Bioscaffold for Volumetric Muscle Loss

Study Overview
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Brief Summary
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This is a prospective, single center study conducted at the University of Pittsburgh designed to test the applicability and utility of XenMatrix™ AB Surgical Graft in the restoration of function in the setting of volumetric muscle loss after soft tissue trauma.

Detailed Description
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Previously, a human subject clinical trial (NCT01292876, PRO10010500) to evaluate a regenerative medicine approach using ECM for VML treatment was conducted. ECM scaffolds were implanted and combined with aggressive and early physical therapy in 13 subjects, then followed for 24-28 weeks after implantation. Histomorphological assessments collected from core needle biopsies identified formation of new, vascularized, innervated islands of skeletal muscle within the implantation site. Subjects demonstrated increased force production in physical therapy evaluations and improved functional task performance when compared with pre-operative performance. By 6 months after ECM implantation, subjects had a 37.3% improvement in strength and 27.1% improvement in range-of-motion tasks. Additionally, changes in nerve conduction study (NCS) and electromyography (EMG) before and after ECM implantation were measured. 63% of study participants experienced improvements in NCS or EMG within the scaffold remodeling site, indicating clinical improvement in muscle strength. The promising functional and regenerative results from this early study encourages evidence of ECM bioscaffolding as a viable treatment to VML. This study proposes to use XenMatrix™ AB Surgical Graft which has 510(k) approval [#K162193] intended for implantation to reinforce soft tissue where weakness exists and for surgical repair of damaged or ruptured soft tissue, including abdominal plastic and reconstructive surgery; muscle flap reinforcement; hernia repair including abdominal, inguinal, femoral, diaphragmatic, scrotal, umbilical, and incisional hernias. The graft has an antibiotic coating, specifically, Rifampin and Minocycline. This coating has been shown in preclinical in vitro and in vivo testing to reduce or inhibit microbial colonization on the device. The claim of reduction of bacterial colonization of the device has not yet been established with human clinical data, nor has a clinical impact associated with this claim been demonstrated and will need further investigation. This trial proposes to test the applicability and utility of XenMatrix™ AB Surgical Graft in the restoration of function in the setting of volumetric muscle loss after trauma. 10 subjects will be enrolled for participation in the study. Prior to Graft implantation, subjects will receive a pre-operative course of physical therapy for a maximum time period of 16 weeks. A physical therapist will confirm that functional plateau is reached prior to implantation of the Graft. Following Graft implantation, radiographic, functional, and electrophysotherapy outcomes will be measured at various time points up to 24-28 weeks post-operatively. A CT scan or MRI will be collected at screening and pre-operative visits to evaluate tissue volume, then again at post-operative Visit 1 and Visit 6. Physical therapy training will be performed as a research procedure following Graft implantation for a maximum of 30 weeks. Additionally, Physical Therapy evaluations will be conducted at screening, pre-op visit 1, post-op, and at post-op Visits 3, and 4. A small core needle biopsy 1-5 grams will be collected at three time points to conduct histomorphological assessment of the tissue prior to Graft implantation (Operative visit, Visit 2 and at Visit 4).

Official Title
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XENMATRIX™ AB Surgical Graft for the Repair of Severe Musculotendinous Tissue Damaged by Soft Tissue Trauma

Conditions
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Muscle Loss

Intervention / Treatment
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* Device: XenMatrix™ AB Surgical Graft


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age: 18 to 70 years of age and able to provide informed consent Civilian, and current or former military personnel are eligible to participate Have suffered injury resulting in a structural deficit of a minimum of 20% of the muscle group mass and a functional deficit of a minimum of 25% when compared to a contralateral limb present; or if bilateral injury is present to extremities, the potential surgical extremity is to be compared against normal expected values of a sample population of similar age and gender and evidence of remaining tendon and musculotendinous units that could be surgically repaired with sutures. Injuries may encompass a single muscle belly or compartment, whether an area is expected to be repaired by sutures will be determined from imaging studies and physical examination. Muscle groups which originate or attach to the long bones of the extremity, and which directly affect strength and function (i.e., Pectoralis Major, Coracobrachialis, Subscapularis, Teres Major/Minor, Latissimus Dorsi, Supraspinatus, Infraspinatus, Gluteus group, Tensor fasciae latae, Piriformis, and quadratus femoris) will also be included in this clinical trial. Have suffered traumatic injury within the last 18 months to the upper and/or lower extremity; Target of 18 months or less but subject's may be enrolled with injury outside this range if the principal investigator determines that there is viable muscle in the injured compartment determined by clinical exam and imaging studies. Eligible for study procedures 3 months post injury with stability determined by the Principal Investigator and/ or Physician Co-Investigator Willing and able to comply with follow up examinations, radiographic studies, physical therapy, muscle biopsy and laboratory tests. Exclusion Criteria: Inability to provide informed consent Poor nutrition (demonstrated by clinically significant abnormal lab results for serum albumin and pre-albumin values, per the investigator's discretion) Chronic disease such as congestive heart failure, liver disease, renal disease, or diabetes Active and unstable disease state or infection anywhere in the body per Physician's evaluation and determination (demonstrated by stated or medical record history and abnormal lab range for CBC with Differential and Platelet, Liver function and chemistry panel values) Known coagulopathy (demonstrated by stated or medical record history of diagnosis) Pregnancy (demonstrated by a positive result of a urine pregnancy test)• Diagnosis of cancer within last 12 months and /or actively receiving chemotherapy or radiation treatment Subjects with an Axis I diagnosis DSM-IV (e.g., Schizophrenia, Bipolar Disorder). Subjects who are found to be stable on medication and receive psychiatric clearance could be eligible for study participation per the Physician's discretion .• Subjects with complete muscle/tendon gaps greater than 5 cm that are obvious on imaging studies and are unlikely to be reasonably repaired with sutures and reinforcement, and will be excluded. The investigators recognize that these findings may not be clear on imaging studies, and that the clinical judgment of the surgeon shall be applied in each case. Subjects with a known hypersensitivity to porcine serum products Allergies to the antibiotics, Rifampin, minocycline, tetracycline currently associated with the XenMatrix AB Surgical Graft Any condition or situation as it relates to the subject's health or safety, that would render concern to the investigators, and therefore preclude subject enrollment in the study.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: XenMatrix AB Surgical Graft<br>This study proposes to use XenMatrix™ AB Surgical Graft which has 510(k) approval [#K162193] intended for implantation to reinforce soft tissue where weakness exists and for surgical repair of damaged or ruptured soft tissue. This trial proposes to test the applicability and utility of XenMatrix™ AB Surgical Graft in the restoration of function in the setting of volumetric muscle loss after trauma | Device: XenMatrix™ AB Surgical Graft<br>* Graft implantation, radiographic, functional, and electrophysotherapy outcomes will be measured at various time points up to 24-28 weeks post-operatively. A CT scan or MRI will be collected at screening and pre-operative visits to evaluate tissue volume, then again at post-operative Visit 1 and Visit 6. Physical therapy training will be performed as a research procedure following Graft implantation for a maximum of 30 weeks. Additionally, Physical Therapy evaluations will be conducted at screening, pre-op visit 1, post-op, and at post-op Visits 3, and 4. A small core needle biopsy 1-5 grams will be collected at three time points to conduct histomorphological assessment of the tissue prior to Graft implantation (Operative visit, Visit 2 and at Visit 4).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| extremity function (number of types of exercises) | Assessment of patient extremity function post implantation of XENMATRIX AB™ Surgical Graft; after skeletal muscle injury, as determined and measured by physical therapy assessments and types of exercises able to do. | 9-11 months | 
| extremity strength (number of repetitions of exercises) | Assessment of patient extremity mechanical strength post implantation of XENMATRIX AB™ Surgical Graft; after skeletal muscle injury as determined by physical therapy assessments and amount of exercise repetitions. | 9-11 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Infection rate | Patient rate of infection with the use of XENMATRIX AB™ Surgical Graft | 9-11 months |