Innovative Treatment of Chemotherapy-Induced Painful Peripheral Neuropathy in Adolescents and Young Adults with Cancer: A two arm pilot study

项目摘要/摘要 据估计，美国五分之一的儿童患有癌症。幸运的是，5年总体存活率 多年来有所改善，目前对许多类型的癌症的治愈率超过80%，这要归功于 化疗。不幸的是，化疗药物有副作用，如周围神经病变(因此- 称为化疗诱导的周围神经病(CIPN)。CIPN是一种令人衰弱的疾病，对 影响受影响患者的生活质量。用于治疗CIPN的药物，如阿片类药物、抗癫痫药、 和抗抑郁药，往往无效，和/或有严重的不良影响，如便秘， 镇静、上瘾、呼吸抑制，甚至死亡。此外，非药物治疗 如经皮电神经刺激(TENS)、针灸和瑜伽，结果喜忧参半。 重要的是，大多数程序已经在患有CIPN的成年人身上进行了测试；而很少有研究进行 在青少年和青壮年(Aya)癌症患者中。因此，AYA患者的CIPN管理 癌症仍然是一个挑战。因此，这个探索性的R21提案解决了治疗中未得到满足的需求 AYAS和CIPN通过引入潜在有效的非侵入性电刺激 这项技术被称为加扰器疗法(ST)，不同于TENS。鉴于其临床表现 AYAS中的CIPN与老年人相似，并得到了最近发表的一项小型研究的支持证据 根据来自意大利的一项研究，我们认为ST是一种有希望的新的治疗方案，适用于所有年龄段的CIPN患者。 因此，这一新的治疗方法值得进一步研究。我们的中心假设是ST显著 减轻疼痛并改善Aya癌症的神经病变、身体功能和生活质量 CIPN患者。为了验证这一假设，我们提出了一个预期的、随机的、等待名单控制的飞行员 有两个特定目的的研究：特定目标1：评价阿亚地区ST治疗CIPN的疗效和安全性 癌症患者和特定目标2：评估ST对身体功能和质量的影响 癌症患者的生活质量(QOL)。这项提案的总体目标是表明ST可能是一种 可有效改善疼痛和疼痛的CIPN药物治疗的有价值的替代方案 应用CIPN改善Aya癌症患者的神经病变和生活质量。我们预计在以下方面将有显著改善 Aya患者CIPN的疼痛等症状负担。最后，这项先导性研究不是机械性研究。 取而代之的是，它将专注于患者报告的结果、身体功能和生活质量，以证明有效性。 因此，疼痛将是我们的主要结果衡量标准，而身体表现和生活质量将是我们的 次要结果衡量标准。长期目标是安全有效地将ST用于所有类型的 顽固性神经性疼痛，如果成功，将导致临床上的变化。

PROJECT SUMMARY/ABSTRACT An estimated one in five children in the United States has cancer. Fortunately, the 5-year overall survival rate has improved over the years and is currently more than 80% for many types of cancer, thanks to advances in chemotherapy. Unfortunately, chemotherapy drugs have adverse effects such as peripheral neuropathy (so- called chemotherapy-induced peripheral neuropathy, CIPN). CIPN is a debilitating condition that negatively affects the quality of life of affected patients. The drugs used to treat CIPN, such as opioids, antiepileptics, and antidepressants, are often ineffective, and/or have profound adverse effects, such as constipation, sedation, addiction, respiratory depression, and even death. Furthermore, nonpharmacologic treatments such as transcutaneous electrical nerve stimulation (TENS), acupuncture, and yoga have shown mixed results. Importantly, most of the procedures have been tested in adults with CIPN; much less research has been done in adolescent and young adult (AYA) cancer patients. Consequently, the management of CIPN in AYA patients with cancer remains a challenge. Thus, this exploratory R21 proposal addresses the unmet need in treating AYAs with CIPN by introducing a potentially effective noninvasive electrocutaneous nerve stimulation technique called scrambler therapy (ST), which is different from TENS. Given that the clinical presentation of CIPN in AYAs is similar to that of older adults, and with supporting evidence from a recently published small study from Italy, we believe that ST is a promising novel treatment option for patients of all ages with CIPN. Thus, it is worth investigating this novel treatment further. Our central hypothesis is that ST significantly reduces pain and improves neuropathy, physical function, and quality of life (QoL) of AYA cancer patients with CIPN. To test this hypothesis, we propose a prospective, randomized, wait-list controlled pilot study with two specific aims: Specific Aim 1: To evaluate the efficacy and safety of ST for CIPN in AYA cancer patients, and Specific Aim 2: To evaluate the impact of ST on physical functioning and quality of life (QoL) in AYA cancer patients. The overall objective of this proposal is to show that ST may be a valuable alternative to pharmacologic management of CIPN that can effectively improve pain and neuropathy and improve QoL for AYA cancer patients with CIPN. We expect to see significant improvement in pain and other symptom burden of CIPN in AYA patients. Finally, this pilot study is not a mechanistic study. Instead, it will focus on patient-reported outcomes, physical functioning, and QoL to demonstrate effectiveness. As such, pain will be our primary outcome measure, whereas physical performance and QoL will be our secondary outcome measures. The long-term goal is to use ST safely and effectively for all types of intractable neuropathic pain, which if successful, will result in changes in the clinic.