BMAC & Allograft vs BMP-2

Study Overview
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Brief Summary
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The aim of this investigation is to compare the use of bone marrow aspirate concentrate (BMAC) and allograft versus recombinant human bone morphogenetic protein-2 (BMP) versus the gold standard fusion in subjects undergoing elective lumbar spinal fusion with interbody support. The safety and efficacy of the surgical interventions will be evaluated by assessing fusion status and subjects' quality of life outcomes.

Detailed Description
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This study will be a prospective, randomized clinical study at a single-center, NYU Langone Medical Center. It is intended to compare and evaluate the efficacy of subjects who are either treated with (1) bone marrow aspirate concentrate (BMAC) and allograft or (2) recombinant human bone morphogenetic protein-2 (BMP) or (3) autograft (control) during lumbar spinal fusion with interbody support. The clinical, radiographic, and Health Related Quality of Life (HRQOL) outcomes will be assessed in operatively treated adult spinal degenerative disease patients undergoing lumbar spinal fusion.

Official Title
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Prospective, Blinded, Non-randomized Study of Thoracolumbar Spinal Fusion Graft Efficacy: Bone Marrow Aspirate Concentrate and Allograft Versus Recombinant Bone Morphogenetic Protein-2 (BMP)

Conditions
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Spinal Fusion

Intervention / Treatment
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* Device: Bone Marrow Aspirate Concentrate (BMAC) + Allograft
* Device: Recombinant Human Bone Morphogenetic Protein-2 (BMP)
* Procedure: Autograft


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Must be 18 years old or older Scheduled for elective posterior or anterior and posterior spinal fusion of the thoracolumbar spine with or without anterior interbody support Failed at least 6 weeks of conservative care No contraindication to BMAC (as per manufacturer) Signed consent form Exclusion criteria: Prior lumbar fusion surgery at operative level (prior discectomy and/or laminectomy allowed) Incompetent or missing anterior arch at the affected level (e.g. laminectomy, pars defect) Currently requires laminectomy at level of surgery Facet joints at implant level are absent or fractured Post-traumatic vertebral body compromise or acute fracture at implant level Body mass Index (BMI) > 40 Known allergy to titanium Paget's disease, osteomalacia, or any other metabolic bone disease Use of medications or any drug known to potentially interfere with bone/soft tissue healing (e.g. chronic systemic steroids) Unlikely to comply with the follow-up evaluation schedule Active malignancy defined as history of invasive malignancy, except if the subject has received treatment and displayed no clinical signs and symptoms for at least five years Pregnant or planning to become pregnant during the length of study participation

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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No

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
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Bone Marrow Aspirate Concentrate (BMAC) + Allograft<br>A total of 60, 120, or 180 mL of BMA to be aspirated. BMA is then placed into the Harvest SmartPrep® Bone Marrow Concentrate (BMAC) system and concentrated to a final volume of 10, 20, or 30 mL. The BMAC will then be combined with packed allograft cancellous bone chips using the Harvest Graft Delivery Pack. The allograft bone will be obtained routinely from the bone bank in the operating suite. If using Harvest Graft Delivery Kit, the BMAC dosing estimate is as follows (BMAC to graft ratio will be 1:1): 1-level fusion: 10 cc of BMAC from 60 cc of BMA (roughly 10 cc of graft) 2-level fusion: 20 cc of BMAC from 120 cc of BMA 3-level fusion: 20 cc of BMAC from 120 cc of BMA 4-level fusion: 180 cc kit 5-level fusion: 240 cc kit If not using Harvest Graft Delivery Kit: Volume of BMAC will be slightly increased (some BMAC will not get directly into hydrating the graft as the BMAC would get lost in the hydration process and left in mixing bowls). | Device: Bone Marrow Aspirate Concentrate (BMAC) + Allograft<br>* Allograft infused with adult stem cells from the bone marrow aspirate harvested from the iliac crest. Harvest BMAC System delivers high stem cell concentration to the graft site.<br>* Other names: Harvest BMAC System;|
| Active Comparator: Recombinant Human Bone Morphogenetic Protein-2 (BMP)<br>12 mL BMP will be applied at the surgical site of the interbody fusion using a collagen sponge following manufacturer's directions. The BMP kit use per level is as follows: 1 Level Fusion: Extra small kit (1.4 cc) 2 Level Fusion: Small Kit (2.8cc) 3 Level Fusion: (4.2 cc) 4 Level Fusion: Medium Kit (5.6cc) 5 Level Fusion: (7.0 cc) | Device: Recombinant Human Bone Morphogenetic Protein-2 (BMP)<br>* INFUSE rhBMP-2 Bone Graft used according to its approved FDA labels, both from an anterior approach using titanium cages as well as from a posterior interbody approach using polyetheretherketone (PEEK) cages.<br>* Other names: INFUSE rhBMP-2;|
| Active Comparator: Autograft<br>As per standard of care, the control group will receive 15cc - 45 cc of allograft with autograft and bone marrow aspirate at each level. The iliac crest is the common donor site for autograft. Using the standard technique for anterior lateral fusion, the bone graft will be laid onto the desired site of fusion. | Procedure: Autograft<br>* Autograft with bone marrow aspirate.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants with Successful Fusion Status at 1 Year Post-Procedure | Fusion status assessed via CT scan by an independent radiologist. | Year 1 | 
| Change in Oswestry Disability Index (ODI) from Baseline | 10-item self-report of how back pain has affected a participant's ability to manage everyday life. Items ranked on a 6-point Likert scale. The total score is the sum of responses; higher scores indicate higher levels of disability: 0 - 4 = No disability; 5 - 14 = Mild disability; 15 - 24 = Moderate disability; 25 - 34 = Severe disability; 35 - 50 = Completely disabled. | Baseline, Year 2 | 
| Change in Visual Analog Scale (VAS) Leg and Back Pain Scores from Baseline | Participants evaluate leg and back pain using a VAS ranging from 0 cm to 10 cm. Lower scores indicate lower levels of pain. | Baseline, Year 2 | 
| Change in Euro-Qol 5-Dimension (EQ-5D) Scores from Baseline | 5-item self-report questionnaire. Each item describes a different aspect of health: Mobility, Self-Care, Usual Activities, Pain/Discomfort, and Anxiety/Depression. Participants rank items on a 3-point Likert scale from 1-3: 1 = no problems; 2 = some problems; 3 = extreme problems. The total score is the sum of responses and ranges from 5-15; lower scores indicate better overall health. | Baseline, Year 2 | 
| Change in Pain Catastrophizing Scale (PCS) from Baseline | Self-report questionnaire containing 13 items that describe different thoughts and feelings that may be associated with pain. Participants rank each item on a Likert scale from 0 (not at all) to 4 (all the time). Scores range from 0 to 52; lower scores indicate lower levels of catastrophic thinking related to pain. | Baseline, Year 2 | 
| Change in Patient Reported Outcome Measure Information System (PROMIS) Item Bank v1.1 - Pain Interference Scores from Baseline | 40-item self-report assessing the negative effects of pain on functioning in the range experienced by the vast majority of people who have pain. Participants rank items on a 5-point Likert scale ranging from 0 to 4. The raw score is the sum of responses and ranges from 0-160; lower scores indicate lower interference from pain. The raw score is translated to give a T-score for each participant. The T-score rescales the raw score into a standardized score with a mean of 50 and a standard deviation (SD) of 10. | Baseline, Year 2 | 
| Change in PROMIS Scale v1.0 - Pain Intensity 3a Scores from Baseline | 3-item self-report assessment of how much a participant hurts. Participants rank items on a 5-point Likert scale ranging from 0 (Had no pain) to 4 (Very severe). The raw score is the sum of responses and ranges from 0-12; lower scores indicate lower levels of pain. The raw score is translated to give a T-score for each participant. The T-score rescales the raw score into a standardized score with a mean of 50 and a standard deviation (SD) of 10. | Baseline, Year 2 | 
| Change in PROMIS Bank v1.2 - Physical Function Scores from Baseline | 120-item self-report assessment of physical health, physical function, pain, and fatigue. Participants rank items on a 5-point Likert scale ranging from 0 to 4. The raw score is the sum of responses and ranges from 0-480; lower scores indicate higher levels of physical function. The raw score is translated to give a T-score for each participant. The T-score rescales the raw score into a standardized score with a mean of 50 and a standard deviation (SD) of 10. | Baseline, Year 2 | 
| Change in PROMIS Bank v2.0 - Mobility Scores from Baseline | 15-item self-report assessment of activities of physical mobility. Each item is ranked on a 5-point Likert scale ranging from 0 to 4. The raw score is the sum of responses and ranges from 0-60; lower scores indicate higher levels of physical mobility. The raw score is translated to give a T-score for each participant. The T-score rescales the raw score into a standardized score with a mean of 50 and a standard deviation (SD) of 10. | Baseline, Year 2 | 
| Length of Hospital Stay |  | From admission up to discharge (Up to Year 2) | 
| Change in Blood Levels during Intraoperative Period | The intraoperative period begins when the patient is transferred to the operating room table and ends when the patient is transferred to the post-anesthesia recovery room. | Beginning of Intraoperative Period (Day 0), End of Intraoperative Period (Day 0) (typically between 2-7 hours). | 
| Change in Blood Levels during Perioperative Period | The perioperative period comprises the preoperative, intraoperative, and postoperative periods. It begins with the decision that surgical intervention is necessary and ends with the complete recovery from surgery. | Beginning of Preoperative Period (Day 0), End of Postoperative Period (Up to Year 2) |