Keats Melanie R, Grandy Scott A, Blanchard Christopher, Fowles Jonathon R, Neyedli Heather F, Weeks Adrienne C, MacNeil Mary V
Division of Kinesiology, School of Health and Human Performance, Dalhousie University, Halifax, NS, Canada.
Division of Medical Oncology, Department of Medicine, Dalhousie University, Halifax, NS, Canada.
JMIR Res Protoc. 2022 May 4;11(5):e37709. doi: 10.2196/37709.
Glioblastoma is the most common primary brain malignancy in adults, accounting for approximately 48% of all brain tumors. Standard treatment includes radiation and temozolomide chemotherapy. Glioblastomas are highly vascular and can cause vasogenic brain edema and mass effect, which can worsen the neurologic symptoms associated with the disease. The steroid dexamethasone (DEX) is the treatment of choice to reduce vasogenic edema and intracranial pressure associated with glioblastoma. However high-dose DEX or long-term use can result in muscle myopathy in 10%-60% of glioblastoma patients, significantly reducing functional fitness and quality of life (QOL). There is a wealth of evidence to support the use of exercise as an adjuvant therapy to improve functional ability as well as help manage treatment-related symptoms. Specifically, resistance training has been shown to increase muscle mass, strength, and functional fitness in aging adults and several cancer populations. Although studies are limited, research has shown that exercise is safe and feasible in glioblastoma populations. However, it is not clear whether resistance training can be successfully used in glioblastoma to prevent or mitigate steroid-induced muscle myopathy and associated loss of function.
The primary purpose of this study is to establish whether an individualized circuit-based program will reduce steroid-induced muscle myopathy, as indicated by maintained or improved functional fitness for patients on active treatment and receiving steroids.
This is a 2-armed, randomized controlled trial with repeated measures. We will recruit 38 adult (≥18 years) patients diagnosed with either primary or secondary glioblastoma who are scheduled to receive standard radiation and concurrent and adjuvant temozolomide chemotherapy postsurgical debulking and received any dose of DEX through the neurooncology clinic and the Nova Scotia Health Cancer Center. Patients will be randomly allocated to a standard of care waitlist control group or standard of care + circuit-based resistance training exercise group. The exercise group will receive a 12-week individualized, group and home-based exercise program. The control group will be advised to maintain an active lifestyle. The primary outcome, muscle myopathy (functional fitness), will be assessed using the Short Physical Performance Battery and hand grip strength. Secondary outcome measures will include body composition, cardiorespiratory fitness, physical activity, QOL, fatigue, and cognitive function. All measures will be assessed pre- and postintervention. Participant accrual, exercise adherence, and safety will be assessed throughout the study.
This study has been funded by the Canadian Cancer Society Atlantic Cancer Research Grant and the J.D. Irving Limited-Excellence in Cancer Research Fund (grant number 707182). The protocol was approved by the Nova Scotia Health and Acadia University's Research Ethics Boards. Enrollment is anticipated to begin in March 2022.
This study will inform how individualized circuit-based resistance training may improve functional independence and overall QOL of glioblastoma patients.
ClinicalTrails.gov NCT05116137; https://www.clinicaltrials.gov/ct2/show/NCT05116137.
INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/37709.
胶质母细胞瘤是成人中最常见的原发性脑恶性肿瘤，约占所有脑肿瘤的48%。标准治疗包括放疗和替莫唑胺化疗。胶质母细胞瘤血管丰富，可导致血管源性脑水肿和占位效应，这会使与该疾病相关的神经症状恶化。类固醇地塞米松（DEX）是减轻与胶质母细胞瘤相关的血管源性脑水肿和颅内压的首选治疗药物。然而，高剂量DEX或长期使用会导致10%-60%的胶质母细胞瘤患者出现肌肉肌病，显著降低功能适应性和生活质量（QOL）。有大量证据支持将运动作为辅助治疗手段，以提高功能能力并帮助管理与治疗相关的症状。具体而言，抗阻训练已被证明可增加老年人和一些癌症患者群体的肌肉量、力量和功能适应性。尽管研究有限，但已有研究表明运动在胶质母细胞瘤患者群体中是安全可行的。然而，尚不清楚抗阻训练是否能成功用于胶质母细胞瘤患者，以预防或减轻类固醇诱导的肌肉肌病及相关功能丧失。
本研究的主要目的是确定基于个体化循环训练的方案是否会减少类固醇诱导的肌肉肌病，这可通过正在接受治疗并使用类固醇的患者功能适应性得以维持或改善来体现。
这是一项双臂随机对照试验，采用重复测量。我们将招募38名成年（≥18岁）患者，他们被诊断为原发性或继发性胶质母细胞瘤，计划在术后减压后接受标准放疗以及同步和辅助替莫唑胺化疗，并通过神经肿瘤门诊和新斯科舍省健康癌症中心接受了任何剂量的DEX。患者将被随机分配到标准护理等待列表对照组或标准护理+基于循环训练的抗阻运动组。运动组将接受为期12周的个体化、团体和居家运动方案。对照组将被告知保持积极的生活方式。主要结局指标，即肌肉肌病（功能适应性），将使用简短体能测试电池和握力进行评估。次要结局指标将包括身体成分、心肺适应性、身体活动、生活质量、疲劳和认知功能。所有指标将在干预前后进行评估。在整个研究过程中，将评估参与者的入组情况、运动依从性和安全性。
本研究由加拿大癌症协会大西洋癌症研究基金和J.D. 欧文有限公司卓越癌症研究基金（资助编号707182）资助。该方案已获得新斯科舍省健康与阿卡迪亚大学研究伦理委员会的批准。预计将于2022年3月开始招募患者。
本研究将为基于个体化循环训练的抗阻训练如何改善胶质母细胞瘤患者的功能独立性和总体生活质量提供信息。
ClinicalTrails.gov NCT05116137；https://www.clinicaltrials.gov/ct2/show/NCT05116137。
国际注册报告识别码（IRRID）：DERR1-10.2196/37709。
