Enhanced Bioscaffold for Volumetric Muscle Loss

Not Applicable

Terminated

Conditions: Muscle Loss

Interventions: Device: XenMatrix™ AB Surgical Graft

Registration Number: NCT04051242

Lead Sponsor: J. Peter Rubin, MD

Brief Summary: 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: 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).

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 10

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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
XenMatrix AB Surgical Graft	XenMatrix™ AB Surgical Graft	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

Primary Outcome Measures

Name	Time	Method
Extremity Function; as Reported by Participant During a Physical Therapy Evaluation, Pre and Post Study Surgical Intervention, Using the Foot and Ankle Ability Measure (FAAM), Activities of Daily Living (ADL) Subscale Score.	Baseline, 6 month follow up	The Foot and Ankle Ability Measure (FAAM) activities of daily living subscale asks respondents to report on whether their activity was limited in the last week due to difficulties with their foot/ankle. The self-assessment uses a 5-point Likert scale from, and has a 6th option, not applicable, if difficulties are not specific to the foot/ankle. Answer choices include No difficulty, slight difficulty, moderate difficulty, extreme difficulty or unable to do. There are two subscales, activities of daily living and sports. For activities of daily living maximum score is 84 and lowest possible score is 0. (For the sports scale the maximum is 28 and the lowest possible score is zero. Higher scores indicate less difficulty with performing the activities. The FAAM sub scores are not totaled together but reported separately). For this subject, due to his injury, the investigators are reporting the Activities of Daily Living Subscale.
Extremity Strength in Right and Left Knee (as Measured by Dynamometry Using Newtons, in a Knee Flexion Force Exercise), Pre and Post Surgical Intervention at Baseline and 6 Month Follow up.	Baseline, 6 month follow up	Assessment of patient extremity mechanical strength in right and left knee, post implantation of XENMATRIX AB™ Surgical Graft; after skeletal muscle injury as determined by physical therapy assessment using knee flexion force, as measured by dynamometry using newtons. Knee flexion force was measured three times, at each timepoint, so both the mean and lowest and highest score are reported below.

Secondary Outcome Measures

Name	Time	Method
Number of Participants With Infection With the Use of XENMATRIX AB™ Surgical Graft	9-11 months	Number of Participants with Infection with the Use of XENMATRIX AB™ Surgical Graft. Two participants received the XENMATRIX AB™ Surgical Graft, during their study surgical intervention.