Clinical Outcomes Associated With the Use of ViviGen® for the Treatment of Lumbar Degenerative Disc Disease

Study Overview
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Brief Summary
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The objective of this study is to perform a prospective, randomized, controlled clinical trial to compare radiographic fusion rates and patient reported outcomes, including pain and function preoperatively and postoperatively, using Depuy ViviGen® Cellular Bone Matrix mixed with cortical/cancellous allograft in conjunction with an approved Depuy Synthes pedicle screw system compared to autograft mixed with cortical/cancellous allograft in conjunction with the same DePuy Synthes pedicle screw system used for a one or two - level posterolateral lumbar fusion.

Detailed Description
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This is a prospective randomized, non-blinded, controlled study. Patients with a diagnosis of degenerative disc disease and/or up to grade I spondylolisthesis and planning to undergo a one or two-level instrumented posterolateral lumbar fusion surgery between L1-S1 will be screened. If eligible and the subject meets all the inclusion criteria and none of the exclusion criteria, the subject will be approached about study participation by the surgeon. If the subject agrees to participate, the consent process will be initiated by the study coordinator. Once the patient has been consented; data including medical history, neurological exam, patient questionnaires (visual analogue pain score (VAS), Oswestry low-back disability questionnaire (ODI), short form health survey (SF-36)) will be collected. Randomization will occur once a surgery date has been scheduled so the appropriate instrumentation can be boarded accordingly. A randomization envelope will reveal randomization treatment group. The envelopes will be generated in a 1:1 fashion and be randomly allocated to an assigned study identification number. Subjects will be randomized to either: 1) treatment arm where the investigator will use an FDA approved/cleared DePuy Synthes spinal pedicle screw system with ViviGen® Cellular Bone Matrix mixed with cortical/cancellous allograft or the 2) control arm where the investigator use the same DePuy Synthes spinal pedicle screw system with local autologous bone graft mixed with cortical/cancellous allograft. Both treatment groups represent standard of care lumbar fusion surgeries using two types of bone graft options to create the arthrodesis as comparators. Once the lumbar fusion surgery has taken place as planned; data will be collected regarding the surgery performed, including operative time, amount of bone graft used, spinal system used, length of hospital stay, and adverse events/complications. Study subjects will be followed up at 6-weeks, 3-months, 6-months, and 12-months postoperatively at the private practice or clinic. During these routine (standard of care) postoperative visits, subjects will complete questionnaires (VAS, ODI, SF-36, patient satisfaction) and have neurological exam (lumbar spine exam, see appendix 1) completed by the investigator. Adverse events related to device and/or procedure will be evaluated as each postoperative visit. Anteroposterior (AP) and lateral x-rays will be performed at all visits with flexion and extension x-rays added at baseline, 3-months, 6-months, and 12-months. A CT scan of the lumbar spine will be performed during the 12-month postoperative time frame at the Beaumont-Royal Oak Imaging Center. Radiographic analysis will be performed and evaluated for fusion status as evidenced by bony bridging, presence of radiolucency, and development of pseudoarthrosis at each follow-up visit. This study design reflects the current standard of care for lumbar spinal stenosis, degenerative disc disease and lumbar degenerative spondylolisthesis. Lumbar fusion surgery using pedicle screw fixation with autograft and allograft bone grafting options is treatment of choice after conservative (non-surgical) therapies have been implemented and failed. Addendum: In order to protect the well-being of patients and in compliance with the current state mandated shelter in place order, follow-up visits will be completed via telephone visit by the study coordinator when possible. This includes patient reported outcomes and adverse event reporting. Some parts of the study visit may not be completed over the phone such as lumbar x-rays, neuro exam, and CT scan (at 12-months postop); these missing (or scheduled at a later date) protocol specific items will be noted as a protocol deviation with the reason being due to COVID-19. If a televisit is not possible, the visit may be rescheduled at a later date. Therefore, out of window and missing visits will be recorded as protocol deviations with the reason being due to COVID-19. Subject follow-up visits will be rescheduled in the office once the acute phase of the pandemic has subsided if the study visit is not substantially out of window. Subject enrollment is on hold until the acute phase of the pandemic has subsided but screening will continue.

Official Title
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Clinical Outcomes Associated With the Use of ViviGen® in Conjunction With Posterolateral Fusion for the Treatment of Lumbar Degenerative Disc Disease

Conditions
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Lumbar Spondylolisthesis, Degenerative Disc Disease, Degenerative Spondylolisthesis, Lumbar Radiculopathy, Lumbar Spinal Stenosis, Lumbar Disc Disease

Intervention / Treatment
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* Combination Product: ViviGen® Cellular Bone Matrix with DePuy Synthes Spinal Pedicle screw system
* Combination Product: Local Bone Autologous Bone Graft with DePuy Synthes Spinal pedicle screw system


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: ≥18 years of age Able to provide consent Is undergoing standard of care one or two-level instrumented posterolateral fusion at the level between L1-S1 Has diagnosis of spinal stenosis, degenerative disc disease and/or up to Grade 1 spondylolisthesis Requires decompression at intended fusion level (multi-level decompression allowed L1-S1) Has failed 6-weeks or more of conservative, non-operative treatment Has back and/or radicular lumbar symptoms with ODI score of ≥ 30 preoperatively. Exclusion Criteria: Any prior lumbar fusion surgery Requires fusion of more than two levels Requires an interbody fusion based on relevant diagnoses and factors (such as foraminal stenosis, degree of spondylolisthesis, spinal deformity, disc space collapse, and subject's age) as determined by investigator BMI > 40 Active systemic infection or infection at operative site History of an osteoporotic fracture and/or vertebral body fracture Is currently being treated with chemotherapy, radiation, immunosuppression or chronic steroid therapy History of osteoporosis, osteopenia, or osteomalacia that would contraindicate spinal surgery Psychological or physical condition in the opinion of the investigator that would interfere with subject self-assessments History of neurological condition in the opinion of the investigator that may affect lumbar function and pain assessments Subjects with a history of cancer must be disease free for at least 3 years Pregnant, or plans on becoming pregnant

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Subjects will be randomized to either: 1) treatment arm where the investigator will use an FDA approved/cleared DePuy Synthes spinal pedicle screw system with ViviGen® Cellular Bone Matrix mixed with cortical/cancellous allograft or the 2) control arm where the investigator use the same DePuy Synthes spinal pedicle screw system with local autologous bone graft mixed with cortical/cancellous allograft. Randomization is 1:1
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: ViviGen® Cellular Bone Matrix with DePuy Synthes Spinal Pedicle Screw System<br>20 subjects undergoing one or two-level instrumented posterolateral lumbar fusion surgery using ViviGen Cellular Bone Matrix mixed with cortical/cancellous allograft and DePuy Synthes pedicle screw system | Combination Product: ViviGen® Cellular Bone Matrix with DePuy Synthes Spinal Pedicle screw system<br>* ViviGen® is manufactured by LifeNet Health. ViviGen® Cellular Bone Matrix is a formulation of cryopreserved viable cortical cancellous bone matrix and demineralized bone. ViviGen is a Human Cells, Tissues, and Cellular and Tissue-based Product (HCT/P) as defined by the U.S. Food and Drug Administration in 21 CFR 1271.10 and will be used with the FDA approved DePuy Synthes Spinal pedicle screw system for fusion.<br>* Other names: ViviGen® Cellular Bone Matrix;|
| Placebo Comparator: Local Bone Autograft with DePuy Synthes Spinal Pedicle Screw System<br>20 subjects undergoing open, one or two-level posterolateral lumbar fusion surgery using local autograft mixed with cortical/cancellous allograft and DePuy Synthes pedicle screw system. | Combination Product: Local Bone Autologous Bone Graft with DePuy Synthes Spinal pedicle screw system<br>* Patient's own bone harvested during spinal surgery will be used with the FDA approved DePuy Synthes spinal pedicle screw system to create the fusion.<br>* Other names: Local Bone Autologous Bone Graft;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of successful Lumbar Fusion measured radiographically | Count of participants with successful lumbar bone fusion as measured by CT scan and flexion/extension x-rays at 12-months as evidenced by the following three criteria: bony bridging, no presence of radiolucency and no development of pseudoarthrosis at the treated lumbar level | 12 months postoperative | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Visual Analog Scale for Pain | Equal to or greater than a 2-point decrease in patient reported outcomes as measured by Visual Analog Scale for pain (0-10 point scale, 0 = no pain and 10 = severe amount of pain) from baseline to 12-months. | 12 months postoperative | 
| Change in Oswestry Disability Index for Pain and Function | Equal to or greater than 15-point decrease in patient reported outcomes as measured by Oswestry Disability Index (0-100 point scale, 0 = least amount of disability, 100 = most severe disability) from baseline to 12-months. | 12 months postoperative | 
| Change in Short Form Health Survey-36 for Quality of Life | Equal to or greater than 15-point increase in patient reported outcomes as measured by SF-36 (0-100 point scale, 0 = low favorable health state and 100 = most favorable health state) from baseline to 12-months. | 12 months postoperative | 
| Neurological Deficit per Lumbar Spine Neurological Exam | Count of participants with new or worsening neurological (lumbar motor and sensory) deficit as evaluated by lumbar spine neurological exam from baseline through 12 months. | 12 months postoperative | 
| Count of participants with revision surgery by month 12 | Count of participants with revision surgery by month 12 | 12 months postoperative | 
| Count of participants developing pseudoarthrosis by month 12 | Count of participants developing pseudoarthrosis by month 12 | 12 months postoperative |