Dataset Information

An open-label randomized multi-Centre study to evaluate anterior controllable Antedisplacement and fusion versus posterior Laminoplasty in patients with cervical ossification of the posterior longitudinal ligament: study design and analysis plan (STAR).

ABSTRACT:

Background

In treating patients with cervical ossification of the posterior longitudinal ligament (COPLL), a novel surgery technique - anterior controllable antedisplacement and fusion (ACAF) suggested promising clinical benefits in recent exploratory studies.

Methods

This is a multicentre, randomized, open-label, parallel-group, active controlled trial that will compare the clinical benefits of ACAF versus conventional posterior laminoplasty (LAMP) in severe COPLL patients. A total of 164 patients will be enrolled and randomized in a 1:1 ratio to either ACAF or LAMP group. The primary efficacy measure is cervical- Japanese Orthopaedic Association (C-JOA) recovery rate at 12 months post operation, which is to be derived by Hirabayashi's method from JOA data (range, 0 [worst] to 17 [normal condition]). Other important secondary efficacy endpoints include visual analogue scale (VAS) pain score (range, 0 [no pain] to 10 [most severe]), 10-item neck disability index (NDI, a total range of 0 to 50 points, the highest index the worst) and 6-level Nurick disability grade (range, 0 [mild] to 5 [severe]). Safety endpoints including adverse events, perioperative complications, and adverse events of special interest will also be assessed in this study. Full analysis set for baseline and efficacy data analyses according to the intention-to-treat principle will be established as the primary analysis population. Analysis of covariance (ANCOVA) will be used to analyze the C-JOA recovery rate, with random stratification factors (if appropriate) and the treatment group as fixed factors, and the baseline level of C-JOA score as covariate.

Discussion

This study is designed to demonstrate the clinical benefits of ACAF as compared to conventional LAMP in COPLL patients. It will provide clinical evidence that the novel surgery technique - ACAF might be more favorable in treating patients with severe cervical ossification of the posterior longitudinal ligament. (Words: 290).

Trial registration

ClinicalTrials.gov number, NCT04968028 .

SUBMITTER: Chen Y

PROVIDER: S-EPMC8425037 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Background:Conventional anterior cervical corpectomy and fusion (ACCF) for cervical ossification of the posterior longitudinal ligament (OPLL) is associated with a high incidence of surgery-related complications. A novel anterior decompression technique [vertebral body sliding osteotomy (VBSO)] has been developed to prevent such complications and achieve effective anterior decompression for severe OPLL patients. The purpose of this study was to describe the procedure of novel surgical technique and to evaluate the long-term surgical outcomes. Methods:Between 2012 and 2014, 24 patients underwent VBSO for treatment of cervical myelopathy caused by severe OPLL. Operation time, estimated blood loss (EBL), neurologic outcomes and perioperative complications were investigated. Various radiographic parameters such as the preoperative canal occupying ratio, postoperative canal widening, and preoperative and postoperative cervical sagittal alignment were also measured. Minimum follow-up was 24 months. Results:The mean Japanese Orthopaedic Association score for cervical myelopathy (C-JOA score) improved from 12.4±2.9 preoperatively to 16.0±1.4 at the final follow-up (P<0.05). The mean recovery rate of the C-JOA score at the final follow-up was 68.65%±17.80%. The mean operating time was 130.7±21.0 minutes and the EBL was 176.3±38.0 mL. There were no perioperative complications. Pseudarthrosis was detected in two cases at 12 months postoperatively. The average spinal canal compromised ratio by OPLL decreased from 64.0%±15.0% preoperatively to 15.5%±12.2% postoperatively (P<0.05), with an average postoperative canal widening of 5.15±1.39 mm. Conclusions:Novel anterior decompression technique termed VBSO may be an effective and safe surgical option for anterior decompression surgery in patients with severe cervical OPLL. Since, VBSO does not involve a direct manipulation of the OPLL mass or dissection of the interspace between the OPLL and dura mater, this may significantly decrease the incidence of surgery-related complications, operation time, and intraoperative blood loss.

Project description:Ossification of the posterior longitudinal ligament (OPLL), a spinal ligament, reduces the range of motion in limbs. No treatment is currently available for OPLL, which is why therapies are urgently needed. OPLL occurs in obesity, is more common in men, and has an onset after 40 years of age. The mechanisms underlying OPLL remain unclear. In this study, we performed a serum proteomic analysis in both OPLL patients and healthy subjects to identify factors potentially involved in the development of OPLL, and found reduced levels of a protein that might underlie the pathology of OPLL. We isolated the protein, determined its amino acid sequence, and identified it as chemokine (C-X-C motif) ligand 7 (CXCL7). Based on these proteomics findings, we generated a CXCL7 knockout mouse model to study the molecular mechanisms underlying OPLL. CXCL7-null mice presented with a phenotype of OPLL, showing motor impairment, heterotopic ossification in the posterior ligament tissue, and osteoporosis in vertebrate tissue. To identify the mechanisms of CXCL7 deficiency in OPLL, we searched for single nucleotide polymorphisms and altered DNA exons, but no abnormalities were found. Although miR-340 levels were found to be high in an miRNA array, they were insufficient to reduce CXCL7 levels. Ubiquitin C-terminal hydrolase1 (UCHL1) was found to be overexpressed in CXCL7-null mice and in the sera of patients with OPLL, and was correlated with OPLL severity. Post-translational modifications of proteins with ubiquitin and ubiquitin-like modifiers, orchestrated by a cascade of specialized ubiquitin activating enzyme (E1), ubiquitin conjugating enzyme (E2), and ubiquitin ligase (E3) enzymes, are thought to control a wide range of cellular processes, and alterations in the ubiquitin-proteasome system have been associated with several degenerative disorders. In addition, the OPLL tissue of CXCL7-null mouse and its primary cells expressed the antibody to ubiquitin (linkage-specific K48). Our data clearly show decreased CXCL7 levels in patients with OPLL, and that OPLL developed in mice lacking CXCL7. Tumor necrosis factor receptor-associated factor (TRAF)6 expression was decreased in CXCL7-null mouse primary cells. Furthermore, K48 polyubiquitination was found in posterior longitudinal ligament ossified tissue and primary cells from CXCL7-null mice. We performed a phosphoproteomics analysis in CXCL7-deficient mice and identified increased phosphorylation of mitogen-activated protein kinase kinase (ME3K)15, ubiquitin protein ligase E3C (UBE3C) and protein kinase C (PKC) alpha, suggesting that ubiquitin-dependent degradation is involved in CXCL7 deficiency. Future studies in the CXCL7-null mouse model are, therefore, warranted to investigate the role of ubiquitination in the onset of OPLL. In conclusion, CXCL7 levels may be useful as a serum marker for the progression of OPLL. This study also suggests that increasing CXCL7 levels in patients can serve as an effective therapeutic strategy for the treatment of OPLL.