Muscle Loss
Conditions
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).
Interventions
DEVICEXenMatrix™ AB Surgical Graft
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).
Sponsors
United States Department of Defense
J. Peter Rubin, MD
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
United States
Participant flow
Recruitment details
10 subjects were consented, and completed in person screening for the study. 7 subjects did not meet eligibility criteria. 3 subjects were found to be eligible to proceed to study surgical intervention. 2 subjects completed the study intervention and received XenMatrix AB. In 1 case, due to a delay from the COVID-19 closure to research at the University of Pittsburgh, the subject no longer met study eligibility, once research was permitted to start.
Participants by arm
| Arm | Count |
|---|---|
| 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
XenMatrix™ AB Surgical Graft: 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). | 10 |
| Total | 10 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Physician Decision | 1 |
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | XenMatrix AB Surgical Graft |
|---|---|
| Age, Continuous | 38.3 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 10 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 10 Participants |
| Region of Enrollment United States | 10 participants |
| Sex: Female, Male Female | 5 Participants |
| Sex: Female, Male Male | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 2 |
| other Total, other adverse events | 2 / 2 |
| serious Total, serious adverse events | 0 / 2 |
Outcome results
Primary
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.
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.
Time frame: Baseline, 6 month follow up
Population: Participant 005 completed the FAAM ADL at baseline, and at 6 months post surgical intervention/implantation of Xenmatrix AB graft.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| XenMatrix AB Surgical Graft | 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 FAAM ADL Sub Score | 69 score on a scale |
| XenMatrix AB Surgical Graft | 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. | 6 month follow up FAAM ADL Sub Score | 73 score on a scale |
Primary
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.
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.
Time frame: Baseline, 6 month follow up
Population: 005, completed both a presurgical/baseline and post-surgical 6 month follow up analysis.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| XenMatrix AB Surgical Graft | 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 right knee flexion force | 18.9 Force, units measured in newtons |
| XenMatrix AB Surgical Graft | 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 left knee flexion force | 12.2 Force, units measured in newtons |
| XenMatrix AB Surgical Graft | 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. | 6 month right knee flexion force | 191.6 Force, units measured in newtons |
| XenMatrix AB Surgical Graft | 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. | 6 month left knee flexion force | 164.4 Force, units measured in newtons |
Secondary
Number of Participants With Infection With the Use of XENMATRIX AB™ Surgical Graft
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.
Time frame: 9-11 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| XenMatrix AB Surgical Graft | Number of Participants With Infection With the Use of XENMATRIX AB™ Surgical Graft | 0 participants |