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: 10670054
• 负责人: Mariana Gross Figueiro
• 金额: $ 69.17万
• 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/10670054
• 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; Phototherapy; 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; improvement on sleep; 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.

项目概要 接受自体干细胞移植（ASCT）的多发性骨髓瘤（MM）患者 经历影响疾病预后、生存和临床显着的负面后遗症 生活质量。这些后遗症包括促炎细胞因子的产生增加， 中性粒细胞减少性发热的发生率较高，症状负担较高（例如抑郁、疼痛） 这与昼夜节律紊乱（CRD）有关。 CRD 涉及破坏 激素分泌、温度和活动自然发生的 24 小时周期。 CRD 提高 促炎细胞因子的产生会产生一系列负面影响，包括 更高的症状负担和发生中性粒细胞减少性发热的风险。 CRD已关联 预后和生存较差。我们最近完成的 R21 研究表明，那天早上 患者病房的昼夜有效照明导致显着更高 夜间褪黑激素水平，减少抑郁症和炎症细胞因子的产生 与昼夜节律无效组（对照组）相比。在活跃组中，改善 观察到睡眠和中性粒细胞减少性发热减少。我们的 R21 结果也显示出强劲的 褪黑激素水平与促炎细胞因子之间呈负相关。因此，对于 在拟议的多中心随机对照试验（RCT）中，我们假设昼夜节律 晨光照射产生的夹带会带来更好的睡眠，降低亲和力水平 炎症细胞因子和症状负担，以及中性粒细胞减少症的发生较少 发烧。我们将调查患者病房/门诊的昼夜节律有效照明 ASCT 期间的设置，促进昼夜节律夹带并改善睡眠，如果昼夜节律 夹带减少炎症。我们还将研究是否有更好的夹带和 较低水平的促炎标记物与较少发生中性粒细胞减少症相关 发烧并减轻症状负担。昼夜节律刺激灯将安装在 门诊环境/医院房间，因为移植在这两种环境中进行。一个独特的 我们干预的优点是不需要任何患者的努力，因为昼夜节律 主动光照射到整个房间。 该项目将确定：1）对昼夜节律有效的光与对昼夜节律无效的光进行比较， ASCT 期间提供的结果导致昼夜节律夹带； 2）昼夜节律的影响 减少促炎症细胞因子并介导昼夜节律有效光对 细胞因子； 3）炎症细胞因子水平的降低与减少 发生中性粒细胞减少性发热并减轻患者的症状负担。