Vertebral Bone Marrow Clot for Spinal Surgery

Study Overview
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Brief Summary
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Spinal fusion (SF) is a common orthopedic procedure to treat spinal diseases. Apart from fixation systems, the procedure requires bone grafting to further improve SF. Cell-based therapies as vertebral bone marrow aspirate (vBMA) with bone allograft were developed as alternative to bone autograft in SF. However, vBMA use is limited by the lack of a standardized procedure, of a structural texture and by the possibility of diffusion away from the implant site. Recently, the potential use of a new formulation of vBMA, named vBMA clot, has been described. The project aims at evaluating the clinical evidence and the biological features of vBMA clot associated to bone allograft for SF surgery, considering age and gender related differences. A randomized controlled trial will prove the efficacy of the treatment and advanced preclinical studies will improve the knowledge on vBMA clot regenerative and anti-inflammatory properties, exploring for the first time its antibacterial characteristics.

Detailed Description
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To evaluate the efficacy of autologous vBMA clot in SF procedures in patients with degenerative spine diseases, a randomized controlled trial (RCT) will be carried out. The study will compare patients treated with autologous vBMA clot associated to bone allograft chips versus bone allograft chips alone (standard treatment), also evaluating whether patient age and gender are associated with differences in the clinical outcomes.

Official Title
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The Vertebral Bone Marrow Clot as Autologous Cell-therapy and Multifunctional Bio-scaffold Targeting the Key Challenges for Spinal Fusion Surgery

Conditions
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Degenerative Spine Diseases

Intervention / Treatment
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* Biological: Vertebral bone marrow (vBMA) clot
* Other: Bone allograft chips


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: degenerative spinal disorders (based radiological diagnosis) posterior spinal stabilization ≤ 5 levels age between 18-80 years at the time of surgery Exclusion Criteria: HIV HBV HCV coagulations disorders pregnant or breast-feeding women cancer infections previous spinal surgery radio- chemotherapy myeloproliferative disease chronic steroid medication, thyroxin, immunodepression

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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: Experimental group - vertebral bone marrow (vBMA) clot<br>Bone allograft chips will be obtained from Istituto Ortopedico Rizzoli while vBMA will be harvested from each patient vertebral pedicle with the preparation of the site for pedicle screw insertion during spinal surgery. After the positioning of pedicle screws, the decompression of the cauda and nerve roots will be achieved with a hemilaminectomy and foraminotomy. vBMA clot associated with bone allograft chips will be opposed on the hemi-laminae and transvers process on the contralateral side of the hemilaminectomy. On the hemilaminectomy side, foramino-arthrectomy will be performed to insert the interbody fusion cage if necessary. After aspiration, the vBMA will be clotted and used for surgical procedure. vBMA clot associated to bone allograft chips will be applied on each side of the vertebra according to the number of segments to be fused. | Biological: Vertebral bone marrow (vBMA) clot<br>* The clotted vBMA will be obtained from vertebral bone marrow aspirate.The vBMA clot contain mesenchymal stem cells (MSCs), growth factors, platelet and osteogenic and anti-inflammatory mediators.<br>|
| Active Comparator: Control - bone allograft chips<br>Bone allograft chips will be obtained from Istituto Ortopedico Rizzoli. In detail, conventional posterior approach for lumbar SF will be performed. After the positioning of pedicle screws, the decompression of the cauda and nerve roots will be achieved with a hemilaminectomy and foraminotomy. Bone allograft chips alone will be opposed on the hemi-laminae and transvers process on the contralateral side of the hemilaminectomy. On the hemilaminectomy side, foramino-arthrectomy will be performed to insert the interbody fusion cage if necessary. | Other: Bone allograft chips<br>* Bone allograft chips will be obtained from Musculoskeletal Tissue Bank at IRCCS Istituto Ortopedico Rizzoli.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Brantigan classification | Improvement of spinal fusion rate and time in patients treated with vBMA clot associated to bone allograft chips in comparison to bone allograft chips alone, also considering age and gender differences. CT-scan and X-ray, perform pre-operatively and at 1, 3, 6, 12 months of FU, will be evaluated basing on Brantigan classification (which ranges from A to E, with E score indicating better SF rate). | At baseline (day 0) | 
| Brantigan classification | Improvement of spinal fusion rate and time in patients treated with vBMA clot associated to bone allograft chips in comparison to bone allograft chips alone, also considering age and gender differences. CT-scan and X-ray, perform pre-operatively and at 1, 3, 6, 12 months of FU, will be evaluated basing on Brantigan classification (which ranges from A to E, with E score indicating better SF rate). | 1 month | 
| Brantigan classification | Improvement of spinal fusion rate and time in patients treated with vBMA clot associated to bone allograft chips in comparison to bone allograft chips alone, also considering age and gender differences. CT-scan and X-ray, perform pre-operatively and at 1, 3, 6, 12 months of FU, will be evaluated basing on Brantigan classification (which ranges from A to E, with E score indicating better SF rate). | 3 months | 
| Brantigan classification | Improvement of spinal fusion rate and time in patients treated with vBMA clot associated to bone allograft chips in comparison to bone allograft chips alone, also considering age and gender differences. CT-scan and X-ray, perform pre-operatively and at 1, 3, 6, 12 months of FU, will be evaluated basing on Brantigan classification (which ranges from A to E, with E score indicating better SF rate). | 6 months | 
| Brantigan classification | Improvement of spinal fusion rate and time in patients treated with vBMA clot associated to bone allograft chips in comparison to bone allograft chips alone, also considering age and gender differences. CT-scan and X-ray, perform pre-operatively and at 1, 3, 6, 12 months of FU, will be evaluated basing on Brantigan classification (which ranges from A to E, with E score indicating better SF rate). | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Re-operation rate | The radiological outcome is the reduction of re-operation rate due to pseudoarthrosis that will be estimate by Brantigan classification. | At baseline (day 0) | 
| Re-operation rate | The radiological outcome is the reduction of re-operation rate due to pseudoarthrosis that will be estimate by Brantigan classification. | 1 month | 
| Re-operation rate | The radiological outcome is the reduction of re-operation rate due to pseudoarthrosis that will be estimate by Brantigan classification. | 3 month | 
| Re-operation rate | The radiological outcome is the reduction of re-operation rate due to pseudoarthrosis that will be estimate by Brantigan classification. | 6 month | 
| Re-operation rate | The radiological outcome is the reduction of re-operation rate due to pseudoarthrosis that will be estimate by Brantigan classification. | 12 month | 
| Visual Analogue Score | Visual Analogue Score (which ranges from 0 to 100 with higher scores indicating more severe pain) | At baseline (day 0) | 
| Visual Analogue Score | Visual Analogue Score (which ranges from 0 to 100 with higher scores indicating more severe pain) | 1 month | 
| Visual Analogue Score | Visual Analogue Score (which ranges from 0 to 100 with higher scores indicating more severe pain) | 3 months | 
| Visual Analogue Score | Visual Analogue Score (which ranges from 0 to 100 with higher scores indicating more severe pain) | 6 months | 
| Visual Analogue Score | Visual Analogue Score (which ranges from 0 to 100 with higher scores indicating more severe pain) | 12 months | 
| Oswestry Disability Index | Oswestry Disability Index (ODI) (which ranges from 0 to 100 with higher scores indicating more severe disability) | At baseline (day 0) | 
| Oswestry Disability Index | Oswestry Disability Index (ODI) (which ranges from 0 to 100 with higher scores indicating more severe disability) | 1 month | 
| Oswestry Disability Index | Oswestry Disability Index (ODI) (which ranges from 0 to 100 with higher scores indicating more severe disability) | 3 months | 
| Oswestry Disability Index | Oswestry Disability Index (ODI) (which ranges from 0 to 100 with higher scores indicating more severe disability) | 6 months | 
| Oswestry Disability Index | Oswestry Disability Index (ODI) (which ranges from 0 to 100 with higher scores indicating more severe disability) | 12 months | 
| Short Form Health Survey 36 | Short Form Health Survey 36 (SF-36) (set of generic and coherent quality-of-life measures based on patient self-reporting outcomes) | At baseline (day 0) | 
| Short Form Health Survey 36 | Short Form Health Survey 36 (SF-36) (set of generic and coherent quality-of-life measures based on patient self-reporting outcomes) | 1 month | 
| Short Form Health Survey 36 | Short Form Health Survey 36 (SF-36) (set of generic and coherent quality-of-life measures based on patient self-reporting outcomes) | 3 months | 
| Short Form Health Survey 36 | Short Form Health Survey 36 (SF-36) (set of generic and coherent quality-of-life measures based on patient self-reporting outcomes) | 6 months | 
| Short Form Health Survey 36 | Short Form Health Survey 36 (SF-36) (set of generic and coherent quality-of-life measures based on patient self-reporting outcomes) | 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Spine, Spinal fusion, Degenerative diseases, Vertebral bone marrow, Clot