A Prospective Study of the Safety and Efficacy of 3D-printed Non-rigid Biomimetic Implant in Cervical and Thoracolumbar Spine

Spinal Tumor Clinical Trial

Official title:

A Prospective Study of the Safety and Efficacy of 3D-printed Custom-made Non-rigid Biomimetic Implant for Anterior Column Reconstruction in Cervical and Thoracolumbar Spine

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05396222
• Other study ID #: 202202015DIPC
• Status: Not yet recruiting
• Phase: N/A
• Start date: December 1, 2023
• Est. completion date: February 4, 2025

Study information

• Verified date: July 2023
• Source: National Taiwan University Hospital
• Contact: Fon-Yih Fon-Yih, PhD
• Phone: 0933759026
• Email: 8d62535[@]gmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Vertebral body resection is a wide accepted procedure in tumor resection, deformity correction, and anterior decompression in spondylosis, ossification of posterior longitudinal ligaments, and spondylodiscitis surgery. However, reconstruction of segmental defect is still challenging to spine surgeon, especially in 3-column resection, such as total en bloc spondylectomy in tumor patients. Various graft or prosthesis for reconstruction has been reported, such as structural allograft, Harms mesh cages, expandable cages, and carbon fiber stackable cages. There are no high evidence level study examining the superiority of those different methods. Recently, 3D printed vertebral body replacement has been reported in different disease entities as well, such as tumor, Kümmell's disease in osteoporosis, and spondylosis. 3D printed implant comes with superiority in production of complex geometries and regularity of the fine surface detailed that promote bone ingrowth. Although, 3D-printed titanium vertebra could achieved bone integration in human, a systemic review showed that the subsidence noted in 31.4% of spine surgery with 3D printed implants. In spine surgery, the fixation construct is sufficiently stiff, interbody motion can be reduced, and loading sharing promotes bone fusion. On the other hand, if the reconstruction is too stiff, stress shielding at fusion site occurs. The concept of dynamic fusion, as opposed to rigid fusion, has been demonstrated by an anterior cervical interbody fusion study in porcine model, demonstrating good bone formation, less postfusion stiffness, and a trend to less subsidence. Thus, we developed a 3D printed, custom-made, biomimetic prosthesis, with non-rigid structure, which has been tested in biomechanical study and porcine model, showing good bone formation and less stiffness as well. Therefore, we proposed a prospective clinical study to investigate safety, subsidence, and fusion of this prosthesis.

Description:

This is a single-arm prospective observational phase I clinical study to investigate the safety of the non-rigid 3D printed custom-made biomimetic implant. The implants are made of Titanium alloy. Patient receiving 1- to 3-level corpectomy at cervical and thoracolumbar spine. At first stage, we plan to enroll 3 cervical patients, and 3 thoracolumbar patients with non-rigid 3D printed custom-made biomimetic reconstructions. After 3 months observation after the last patients enrolled, we will conduct an interim investigation to investigate those 6 patients. if there is no re-operations due to acute post-operative reconstruction failure. We will continue the study. Total 9 cervical patients, and 9 thoracolumbar patients will be enrolled. Patients are evaluated preoperatively, right after surgery, and 1, 3, 6, 12 months postoperatively. Measure outcomes included overall success, VAS neck and back pain, patient satisfaction, anxiety score, SF-12 MCS/PCS, complications, subsequent surgery rate, and subsidence and fusion rate on radiological examination. Radiological evaluation, including X-ray and computed tomography, will be done pre-operatively, immediately after the surgery, and 1, 3, 6, 12 months postoperatively. In addition, neck disability index (NDI) will be evaluated in cervical patents, and SORGSQ 2.0 self-reported questionnaire will be applied for all oncology patients. The primary endpoint was a FDA composite definition of success comprising clinical improvement and absence of major complications and secondary surgery events.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 18
• Est. completion date: February 4, 2025
• Est. primary completion date: June 1, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 20 Years to 79 Years

Eligibility

Inclusion Criteria:

1. Age 20 - 79 years;

2. Patient meet the indication for 1- to 3- level corpectomy, for primary bone tumor at spine, or metastatic tumor at spine.

3. Deficit confirmed by CT, MRI, and X-ray;

4. Pathology level located from C3 to L5.

5. Physically and mentally able and willing to comply with the protocol;

6. Signed informed consent;

7. NTU Spine Multidisciplinary Board confirmed tumor excision surgery is indicated.

8. Life expectancy longer than 6 months (Tokuhashi Scoring System)

Exclusion Criteria:

1. Patient does not meet the indication of corpectomy, which is under the surveillance.

2. More than three vertebrae required corpectomy;

3. Corpectomy levels above C3 and below L5

4. T-score less than -2.5

5. Known allergy to device materials - such as titanium

6. Any diseases or conditions that would preclude accurate clinical evaluation;

7. Daily, high-dose oral and/or inhaled steroid or a history of chronic use of high dose steroids;

8. BMI > 35

9. Life expectancy less than 6 months - (Tokuhashi Scoring System)

10. The subject has received radiation therapy or chemotherapy at the trial site within one year;

11. Anterior spine surgery has been received at or near the spine surgery site;

12. The subject has systemic infection,or focal vertebral infection or trauma;

13. The subject has endocrine disorders or metabolic disorders known to affect bone formation, such as: Paget's disease, renal osteodystrophy, hypothyroidism;

14. The subject has neuromuscular diseases, those at risk of instability, implant fixation failure or postoperative care complications, including: spina bifida, cerebral palsy, and multiple sclerosis;

15. Osteopenia, osteomyelitis;

16. Pregnant women.

Related Conditions & MeSH terms

• Spinal Cord Neoplasms
• Spinal Neoplasms
• Spinal Tumor

Intervention

Device:
• 3D-printed custom-made non-rigid biomimetic implant
We developed a 3D printed, custom-made, biomimetic prosthesis, with non-rigid structure, which has been tested in biomechanical study and porcine model, showing good bone formation and less stiffness as well. Therefore, we proposed a prospective clinical study to investigate safety, subsidence, and fusion of this prosthesis.

Locations

Country	Name	City	State
Taiwan	National Taiwan University Hospital	Taipei

Sponsors (1)

Lead Sponsor	Collaborator
National Taiwan University Hospital

Country where clinical trial is conducted

Taiwan, 

References & Publications (17)

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Bridwell KH, Lenke LG, McEnery KW, Baldus C, Blanke K. Anterior fresh frozen structural allografts in the thoracic and lumbar spine. Do they work if combined with posterior fusion and instrumentation in adult patients with kyphosis or anterior column defe — View Citation

Choy WJ, Mobbs RJ, Wilcox B, Phan S, Phan K, Sutterlin CE 3rd. Reconstruction of Thoracic Spine Using a Personalized 3D-Printed Vertebral Body in Adolescent with T9 Primary Bone Tumor. World Neurosurg. 2017 Sep;105:1032.e13-1032.e17. doi: 10.1016/j.wneu.2 — View Citation

Dong C, Wei H, Zhu Y, Zhou J, Ma H. Application of Titanium Alloy 3D-Printed Artificial Vertebral Body for Stage III Kummell's Disease Complicated by Neurological Deficits. Clin Interv Aging. 2020 Dec 2;15:2265-2276. doi: 10.2147/CIA.S283809. eCollection — View Citation

Dvorak MF, Kwon BK, Fisher CG, Eiserloh HL 3rd, Boyd M, Wing PC. Effectiveness of titanium mesh cylindrical cages in anterior column reconstruction after thoracic and lumbar vertebral body resection. Spine (Phila Pa 1976). 2003 May 1;28(9):902-8. doi: 10. — View Citation

Fang T, Zhang M, Yan J, Zhao J, Pan W, Wang X, Zhou Q. Comparative Analysis of 3D-Printed Artificial Vertebral Body Versus Titanium Mesh Cage in Repairing Bone Defects Following Single-Level Anterior Cervical Corpectomy and Fusion. Med Sci Monit. 2021 Feb — View Citation

Girolami M, Boriani S, Bandiera S, Barbanti-Brodano G, Ghermandi R, Terzi S, Tedesco G, Evangelisti G, Pipola V, Gasbarrini A. Biomimetic 3D-printed custom-made prosthesis for anterior column reconstruction in the thoracolumbar spine: a tailored option fo — View Citation

Girolami M, Sartori M, Monopoli-Forleo D, Ghermandi R, Tedesco G, Evangelisti G, Pipola V, Pesce E, Falzetti L, Fini M, Gasbarrini A. Histological examination of a retrieved custom-made 3D-printed titanium vertebra : Do the fine details obtained by additi — View Citation

Glennie RA, Rampersaud YR, Boriani S, Reynolds JJ, Williams R, Gokaslan ZL, Schmidt MH, Varga PP, Fisher CG. A Systematic Review With Consensus Expert Opinion of Best Reconstructive Techniques After Osseous En Bloc Spinal Column Tumor Resection. Spine (Ph — View Citation

Lewandrowski KU, Hecht AC, DeLaney TF, Chapman PA, Hornicek FJ, Pedlow FX. Anterior spinal arthrodesis with structural cortical allografts and instrumentation for spine tumor surgery. Spine (Phila Pa 1976). 2004 May 15;29(10):1150-8; discussion 1159. doi: — View Citation

Viswanathan A, Abd-El-Barr MM, Doppenberg E, Suki D, Gokaslan Z, Mendel E, Rao G, Rhines LD. Initial experience with the use of an expandable titanium cage as a vertebral body replacement in patients with tumors of the spinal column: a report of 95 patien — View Citation

Wallace N, Schaffer NE, Aleem IS, Patel R. 3D-printed Patient-specific Spine Implants: A Systematic Review. Clin Spine Surg. 2020 Dec;33(10):400-407. doi: 10.1097/BSD.0000000000001026. — View Citation

Wei F, Li Z, Liu Z, Liu X, Jiang L, Yu M, Xu N, Wu F, Dang L, Zhou H, Li Z, Cai H. Upper cervical spine reconstruction using customized 3D-printed vertebral body in 9 patients with primary tumors involving C2. Ann Transl Med. 2020 Mar;8(6):332. doi: 10.21 — View Citation

Wei F, Xu N, Li Z, Cai H, Zhou F, Yang J, Yu M, Liu X, Sun Y, Zhang K, Pan S, Wu F, Liu Z. A prospective randomized cohort study on 3D-printed artificial vertebral body in single-level anterior cervical corpectomy for cervical spondylotic myelopathy. Ann — View Citation

Xu N, Wei F, Liu X, Jiang L, Cai H, Li Z, Yu M, Wu F, Liu Z. Reconstruction of the Upper Cervical Spine Using a Personalized 3D-Printed Vertebral Body in an Adolescent With Ewing Sarcoma. Spine (Phila Pa 1976). 2016 Jan;41(1):E50-4. doi: 10.1097/BRS.00000 — View Citation

Yang SH, Xiao FR, Lai DM, Wei CK, Tsuang FY. A Dynamic Interbody Cage Improves Bone Formation in Anterior Cervical Surgery: A Porcine Biomechanical Study. Clin Orthop Relat Res. 2021 Nov 1;479(11):2547-2558. doi: 10.1097/CORR.0000000000001894. — View Citation

Yang X, Wan W, Gong H, Xiao J. Application of Individualized 3D-Printed Artificial Vertebral Body for Cervicothoracic Reconstruction in a Six-Level Recurrent Chordoma. Turk Neurosurg. 2020;30(1):149-155. doi: 10.5137/1019-5149.JTN.25296-18.2. — View Citation

* Note: There are 17 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of participants with treatment-related adverse events as assessed by CTCAE v4.0	We will follow up the condition of participants with treatment-related adverse events as assessed by CTCAE v4.0.	Patient were evaluated at 12 months postoperatively.
Secondary	Degree of change in the subsidence	In a medical sense, subsidence refers to the collapse or settling of bone located immediately next to an implantable device in direction of the loading force. It is uasually recorded in millimeters. It was assessed on radiological examination. Radiological evaluation, including X-ray and computed tomography.	Patient were evaluated pre-operatively, immediately after the surgery, and 1, 3, 6, 12 months postoperatively.
Secondary	The percentage of patients with successful fusion	The fusion rate is the percentage of patients with successful fusion over a specific range of follow up. The outcomes about fusion rate of bone was assessed on radiological examination. Radiological evaluation, including X-ray and computed tomography.	Patient were evaluated pre-operatively, immediately after the surgery, and 1, 3, 6, 12 months postoperatively.
Secondary	Pain score	Pain score was assessed by Visual Analogue Scale. (0 means no pain, while 10 is the most painful situation).	Patient were evaluated pre-operatively, immediately after the surgery, and 1, 3, 6, 12 months postoperatively.
Secondary	Short form-12 mental component score	The minimum value of mental component scale (MCS-12) is 18.7, and the maximum value of MCS-12 is 65.2. Higher scores mean a better outcome.	Patient were evaluated pre-operatively, immediately after the surgery, and 1, 3, 6, 12 months postoperatively.
Secondary	Anxiety score	Anxiety score was assessed by Beck Anxiety Inventory (The minimum value is 0 and the maximum value is 63. A higher score means a worse outcome).	Patient were evaluated pre-operatively, immediately after the surgery, and 1, 3, 6, 12 months postoperatively.
Secondary	Neck Disability Index (NDI)	Physical function was assessed by Neck Disability Index (NDI), it will be evaluated only in cervical patents.; An improvement in Neck Disability Index (NDI) score of at least 30 points for a patient with a preoperative NDI score of 60 or greater; or an improvement of at least 50% of preoperative NDI score for patients with a preoperative score of less than 60.	Patient were evaluated pre-operatively, immediately after the surgery, and 1, 3, 6, 12 months postoperatively.
Secondary	Patient Satisfaction Questionnaire	Patients will be surveyed by Patient Satisfaction Questionnaire. There are two questions on the questionnaire to evaluate if they are satisfied with their treatment and if they will recommend their respective surgery to a friend.	Patient were evaluated pre-operatively, immediately after the surgery, and 1, 3, 6, 12 months postoperatively.
Secondary	Short form-12 physical component score	The minimum value of physical component scale (PCS-12) is 18.4 and the maximum value of PCS-12 is 57.8.	Patient were evaluated pre-operatively, immediately after the surgery, and 1, 3, 6, 12 months postoperatively.