Randomized controlled clinical trial of botulinum toxin for myofascial TMJD pain

描述（由申请人提供）：虽然文献中很少有证据表明肉毒毒素A （BoNT/A）对这种适应症是安全或有效的，但肉毒毒素A （BoNT/A）最近作为一种治疗选择，受到了持续性肌筋膜颞下颌肌和关节疾病（TMJD）患者的强烈兴趣。如果将其注射到咀嚼肌中是安全有效的，那么对于许多对现有治疗方式没有反应的TMJD患者来说，它将证明是无价的。一些研究报告了模棱两可的疗效证据，但仔细检查表明，这些研究要么力度不足，要么控制不力。另一方面，尽管临床前研究表明，注射咀嚼肌后下颌髁突形态发生了深刻变化，牙槽骨丢失，但BoNT/A在TMJD患者中的安全性尚未得到很好的评估。为了解决这两个问题，我们提出了一项随机、双盲、安慰剂对照临床试验（RCCT），其中为期一个月的运行，然后间隔3个月进行两次治疗，并进行3个月的随访。符合研究诊断标准的肌筋膜颞下颌关节痛患者（每组51例）将被随机分配接受BoNT/A或生理盐水注射。在第二个疗效随访期后，分配到BoNT/A的患者将进行额外的治疗周期和3个月的随访，以进一步评估骨相关变化。本临床试验将确定单次和多次注射的效果

DESCRIPTION (provided by applicant): While the literature provides little evidence that it is either safe or efficacious for this indication, Botulinum toxin A (BoNT/A) has received keen recent interest as a treatment option for patients with persistent myofascial temporomandibular muscle and joint disorder (TMJD). Were it shown to be safe and effective when injected into the masticatory muscles, it could prove invaluable to the many TMJD patients who do not respond to existing treatment modalities. Several studies have reported equivocal evidence of efficacy, but close inspection shows that those studies were either underpowered and/or poorly controlled. BoNT/A safety, on the other hand, has not been well assessed in TMJD patients, despite the fact that preclinical studies suggest profound changes in the morphology of the mandibular condyle and loss of alveolar bone following injection of the masticatory muscles. To address both of these issues, we propose a randomized, double-blind, placebo-controlled clinical trial (RCCT) with a one month run-in followed by two treatments spaced 3 months apart and a 3 month follow-up. Myofascial TMJD patients (51 per group) who meet Research Diagnostic Criteria will be randomly assigned to receive either BoNT/A or saline vehicle injections. After the second efficacy follow-up period, patients assigned to BoNT/A will be followed for an additional treatment cycle and 3 month follow-up period, to further assess bone-related changes. This clinical trial will determine the effect of single and repeated injections of BoNT/A into the masseter, temporalis and lateral pterygoid muscles on changes in (1) spontaneous and elicited pain intensity, (2) masticatory muscle function, and (3) density, volume and morphology of the mandible and maxilla in regions supporting the posterior teeth, as well as the mandibular condyle. The R34 planning period for this RCCT will be used to develop a full protocol and MOP, address regulatory issues, obtain IRB approval, plan for data safety monitoring, and finalize a detailed protocol for cone-beam CT based evaluation of bone-related changes indicating potential safety risks. This study not only satisfies NIDCR's mission to support innovative clinical research to improve craniofacial health, but it will also provide key information, regardless of the direction of the results, critical for evidence-based clinical practce. PUBLIC HEALTH RELEVANCE: Evidence that BoNT/A is either a safe or efficacious treatment option for myofascial TMJD is lacking. As such, use of BoNT/A for TMJD pain presents a potential public health issue. This study not only satisfies NIDCR's goal of supporting innovative clinical research to improve craniofacial health; it has also been designed to provide key information, regardless of the direction of the results, critical for evidence based clinical practce.