Multi-site Randomized Clinical Trial of FIT Teens for Juvenile Fibromyalgia

青少年纤维肌痛（JFM）是一种复杂的，慢性的，使人衰弱的疼痛状况，目前尚无治愈方法 治疗选择有限。我们的多学科专家团队在行为医学，流变学， 运动科学和疼痛医学已经开发出一种新的非药物干预-纤维肌痛 青少年综合训练计划（FIT Teens）目前正在严格的3臂多站点测试中进行 一项随机对照试验（RCT），以检查FIT Teens是否比CBT更有效地减少残疾 在3个月的主要终点时，单独进行分级有氧运动（CBT）或单独进行分级有氧运动（GAE）， 效果是持续的。FIT Teens RCT是迄今为止最大（N=420）和最严格的JFM治疗试验 我们已经建立了一个强大的RCT基础设施，包括集中的数据协调中心和临床试验中心。 协调中心有六个临床站点。该试验于2018年成功启动，正在积极招募中 及治疗患者，直至二零二零年三月宣布新冠肺炎疫情为公共卫生紧急状态。中断 大流行给试验造成的延误远远超出了通常缺乏诊所和偏远地区的情况， 由于本试验的独特情况，影响大多数试验的工作，即，儿科年龄范围内的患者， 疫苗在很长一段时间内无法获得，以及在以下地区实施的安全性/可行性问题- 以人为本的干预措施。因此，我们迅速将整个试验转向远程医疗格式 并在暂停新入组6个月后，成功重新启动试验并建立了 入学率轨迹与大流行前的水平相当。我们目前招募了N=330名JFM参与者 (78.5%的建议样本量），并具有良好的保留（>80%）和啮合。dsmb和 NIAMS已批准将试验时间轴延长至2024年5月，以完成入组、治疗和 随访该试验目前处于第1年（2022年6月1日至2023年5月31日）的无成本延长期。有了结转资金， 我们能够减轻疫情造成的延误的部分影响，但我们只能实施 审判至2022年10月31日，之后资金耗尽。我们提交这份紧急行政补充文件 由于成功完成试验急需资金（从2022年11月1日至2024年5月31日）而提出请求。 如果没有额外的资金，对这一重要审判的巨大投资将处于危险之中，因为我们将 没有足够的数据来测试我们的主要目标。审判的完成将明确显示，如果没有- 药物治疗是真正安全有效的长期解决慢性疼痛问题的方法， 青少年残疾与JFM。此外，我们将有独特的机会来审查可接受性， 以远程格式实施FIT Teens干预的安全性和初步效应量。这可能 通过远程医疗为FIT青少年治疗提供信息传播工作，这将是令人难以置信的进步， 外地辅助项目已经对JFM的神经病理生理学产生了重要的见解， 运动生物力学可能是未来JFM治疗的范式转变。

Juvenile-onset fibromyalgia (JFM) is a complex, chronic, and debilitating pain condition for which there is no cure and treatment options are limited. Our multidisciplinary team of experts in Behavioral Medicine, Rheumatology, Exercise Science and Pain Medicine have developed a novel non-pharmacologic intervention - the Fibromyalgia Integrative Training program for Teens (FIT Teens) which is currently being tested in a rigorous 3-arm multi-site randomized controlled trial (RCT) to examine whether FIT Teens is more effective in reducing disability than CBT alone (CBT) or graded aerobic exercise alone (GAE) at the 3-month primary endpoint and whether treatment effects are sustained. The FIT Teens RCT is the largest (N=420) and most rigorous trial for JFM treatment to date and we have established a robust RCT infrastructure with a centralized Data Coordinating Center and Clinical Coordinating Center with six clinical sites. The trial was successfully launched in 2018 and was actively enrolling and treating patients until the COVID19 public health emergency was declared in March 2020. The disruption and delay that the pandemic caused for the trial went far beyond the typical lack of access to clinics and remote work that affected most trials due to circumstances unique to this trial – i.e., patients in a pediatric age range for whom vaccines were not available for an extended time, and the safety/feasibility concerns of implementing in- person group-based interventions. Therefore, we rapidly pivoted the entire trial to remote telehealth format and after a 6-month suspension of new enrollment, were able to successfully re-launch the trial and establish an enrollment trajectory comparable to pre-pandemic levels. We have currently enrolled N=330 JFM participants (78.5% of the proposed sample size) and have excellent retention (>80%) and engagement. The DSMB and the NIAMS have approved an extension of the trial timeline to May 2024 to complete enrollment, treatment and follow-up. The trial is currently in No-Cost Extension Year 1 (06/01/2022 – 05/31/2023). With carry-over funds, we are able to mitigate some of the impact of the delay caused by the pandemic but we can only implement the trial until 10/31/2022, after which funds run out. We are submitting this urgent Administrative Supplement Request as a result of the critical need for funds (from 11/1/2022-5/31/2024) to successfully complete the trial. Without additional funds, the enormous investment into this important trial will be in jeopardy because we will not have sufficient endpoint data to test our primary aims. Completion of the trial would definitively show if non- pharmacologic treatment is truly safe and effective long-term solution to the problem of chronic pain and disability in youth with JFM. Additionally, we will have the unique opportunity to examine the acceptability, safety and preliminary effect sizes for implementing the FIT Teens intervention in remote format. This could inform dissemination efforts for the FIT Teens treatment via telehealth which would be an incredible advance for the field. Ancillary projects are already yielding important insights into the neural pathophysiology of JFM and movement biomechanics that could be paradigm-shifting for JFM treatment in the future.