Systematic Light Exposure Effects on Circadian Rhythms Entrainment, Inflammation, Neutropenic Fever and Symptom Burden among Multiple Myeloma Patients undergoing Autologous Stem Cell Transplantation

系统性光照对接受自体干细胞移植的多发性骨髓瘤患者的昼夜节律拖累、炎症、中性粒细胞减少性发热和症状负担的影响

• 批准号: 10392164
• 负责人: Mariana Gross Figueiro
• 金额: $ 72.81万
• 依托单位: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-07-22 至 2027-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10392164
• 关键词: 6-sulfatoxymelatonin; Affect; Autologous Stem Cell Transplantation; Biological; CCL2 gene; Circadian Rhythms; Data; Doctor of Medicine; Drowsiness; Engraftment; Ensure; Equipment and supply inventories; Exposure to; Hormone secretion; Hospitals; Hour; Inflammation; Inflammatory; Interleukin-6; Intervention; Intervention Studies; Light; Lighting; Measures; Mediating; Melatonin; Mental Depression; Multiple Myeloma; Neutropenic Fever; Outpatients; Pain; Pathway interactions; Patients; Patients' Rooms; Phase; Production; Prognosis; Public Health; Quality of life; Randomized Controlled Trials; Recovery; Research; Rest; Risk; Site; Sleep; Sleep Wake Cycle; Symptoms; System; TNF gene; Temperature; Testing; Time; Transplant Recipients; Transplantation; Urine; actigraphy; associated symptom; cancer therapy; circadian; clinically significant; cytokine; design; disease prognosis; experience; follow-up; improved; inflammatory marker; innovation; intervention effect; psychologic; public health relevance; reduce symptoms; side effect; sleep onset; sleep quality; urinary

PROJECT SUMMARY Multiple Myeloma (MM) patients undergoing Autologous Stem Cell Transplantation (ASCT) experience clinically significant negative sequelae affecting disease prognosis, survival, and quality of life. These sequelae include increase in production of pro-inflammatory cytokines, higher occurrences of neutropenic fever and higher symptom burden (e.g., depression, pain) which are associated with circadian rhythm disruption (CRD). CRD involves disruption in naturally occurring 24-hour cycles of hormone secretion, temperature and activity. CRD raises production of pro-inflammatory cytokines unfolding a cascade of negative effects that include higher symptom burden and risk of developing neutropenic fever. CRD has been associated with poorer prognosis and survival. Our recently completed R21 study showed that morning circadian-effective illumination of patients' hospital rooms resulted in significantly higher nocturnal melatonin levels, reduced depression and production of inflammatory cytokines compared to the circadian-ineffective group (control). In the active group, an improvement in sleep and reduction in neutropenic fever was observed. Our R21 results also showed a strong negative relationship between melatonin levels and pro-inflammatory cytokines. Therefore, for the proposed multi-site randomized controlled trial (RCT) we hypothesize that circadian entrainment resulting from morning light exposure will lead to better sleep, lower levels of pro- inflammatory cytokines and symptom burden, as well as fewer occurrences of neutropenic fever. We will investigate if circadian-effective illumination, of patients' hospital rooms/outpatient settings during ASCT, promotes circadian entrainment and improves sleep, and if circadian entrainment reduces inflammation. We will also investigate whether better entrainment and lower levels of pro-inflammatory markers are associated with fewer occurrences of neutropenic fever and reduced symptom burden. The circadian stimulating light will be installed in the outpatient setting/hospital rooms since transplants are performed in both settings. A unique advantage of our intervention is that it does not require any patient effort because the circadian- active light is delivered throughout the entire room. The project will determine if: 1) circadian-effective light compared to circadian-ineffective light, delivered during ASCT results in circadian rhythm entrainment; 2) circadian entrainment reduces pro-inflammation cytokines and mediates the effects of circadian-effective light on the cytokines; and 3) reduced levels of inflammatory cytokines are associated with reduced occurrence of neutropenic fever and lower symptom burden in patients.

项目摘要 接受自体干细胞移植（ASCT）的多发性骨髓瘤（MM）患者 经历临床上显着的负后遗症，影响疾病的预后，生存和 生活质量。这些后遗症包括增加促炎细胞因子的产生， 中性粒细胞热和症状负担更高（例如，抑郁，疼痛）的发生较高 与昼夜节律破坏有关（CRD）。 CRD涉及中断 天然发生的24小时激素分泌，温度和活性。 CRD加剧 产生促炎性细胞因子，展现了一系列负面影响，包括 更高的症状负担和患中性粒细胞热的风险。 CRD一直关联 预后较差和生存。我们最近完成的R21研究表明那天早上 患者病房的昼夜节律有效的照明导致明显更高 夜间褪黑激素水平，抑郁症降低和炎症细胞因子的产生 与昼夜节律群体（对照）相比。在活跃的群体中，有所改善 观察到中性粒细胞热的睡眠和减少。我们的R21结果也显示出强大 褪黑激素水平与促炎细胞因子之间的负相关关系。因此，是 拟议的多站点随机对照试验（RCT）我们假设该昼夜节律 早晨暴露导致的夹带会导致更好的睡眠，较低的利润水平 炎症细胞因子和症状负担，中性粒细胞减少症的发生 发烧。我们将调查患者病房/门诊的昼夜节律有效的照明是否存在 ASCT期间的设置，促进昼夜节律夹带并改善睡眠，如果 夹带减少炎症。我们还将调查更好的夹带和 较低的促炎标志物与中性粒细胞减少症的发生较少有关 发烧和症状负担减轻。昼夜节律的刺激光将安装在 由于在两个设置中进行移植，因此门诊/医院室。一个独特的 我们干预的优势是，它不需要任何患者的努力，因为昼夜节律 - 主动灯在整个房间内交付。 该项目将确定是否：1）与昼夜节律的光线相比，昼夜节律有效的光， 在ASCT期间交付的昼夜节律夹带； 2）昼夜节律夹带 减少促炎细胞因子并介导昼夜节律对 细胞因子； 3）炎症细胞因子的水平降低与降低有关 患者中性粒细胞热和症状负担较低。