A multi-component non-pharmacological intervention to improve cognitive outcomes in hematologic cancer survivors

一种多成分非药物干预措施，可改善血液癌症幸存者的认知结果

• 批准号: 10437361
• 负责人: Noha Sharafeldin
• 金额: $ 7.43万
• 依托单位: UNIVERSITY OF ALABAMA AT BIRMINGHAM
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-05-24 至 2024-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10437361
• 关键词: Address; Adherence; Affect; Age; Aging; Alabama; Allogenic; Alzheimer' s Disease; Appointment; Area; Attention; Attention Concentration; Autologous; Blood; Blood - brain barrier anatomy; Bone Marrow Transplantation; Brain; Cancer Survivor; Cancer Survivorship; Cognition; Cognitive; Cognitive deficits; Complex; Consent; DNA Repair Gene; DNA Repair Pathway; Data; Education; Educational Intervention; Elderly; Energy-Generating Resources; Enrollment; Evaluable Disease; Fatigue; Future; General Population; Glucose; Goals; Hematologic Neoplasms; High Prevalence; Home; Homeostasis; Impaired cognition; Impairment; Income; Inflammation; Infrastructure; Intervention; Ketone Bodies; Ketosis; Learning; Longitudinal prospective study; Measures; Memory; Metabolic; Metabolic Pathway; Molecular; Morbidity - disease rate; Nutritional; Outcome; Pathway interactions; Patients; Pharmaceutical Preparations; Phenotype; Pilot Projects; Plasma; Population; Prospective Studies; Quality of life; Randomized; Randomized Clinical Trials; Research; Research Personnel; Risk; Self Management; Short-Term Memory; Standardization; Supplementation; Survivors; Synaptic plasticity; Testing; Transplant Recipients; Transplantation; Treatment Efficacy; Universities; Waiting Lists; Work; adverse outcome; arm; base; cancer therapy; cellular targeting; cognitive function; cognitive reserve; cognitive testing; cognitive training; comparison intervention; computerized; executive function; experience; future implementation; genetic variant; high risk; improved; interest; intervention effect; intervention program; ketogentic; male; mild cognitive impairment; mortality; multi-component intervention; multidisciplinary; novel; phase III trial; processing speed; programs; sex; survival outcome; telomere; treatment arm; treatment effect; trial design; water solubility

PROJECT SUMMARY / ABSTRACT Cognitive impairment is a well-established adverse outcome in survivors of hematologic malignancy (HM) treated with and without blood or marrow transplantation (BMT). Cognitive impairment significantly challenges survivors’ independence and ability to return to work, in addition to reducing their ability to follow complex treatment management plans which has been associated with worse survival outcomes in older adults with HM. In a large prospective study of HM patients treated with BMT, we found a high prevalence (up to 36%) of global cognitive deficits, which persisted up to 3y. Older age, male sex, lower education and income, lower cognitive reserve, as well as genetic variants on blood brain barrier, telomere homeostasis, and DNA repair genes were associated with increased risk of cognitive impairment. In order to address the need to mitigate the risk of cognitive deficits, we conducted a study to examine the feasibility of a 12-week, home-based, cognitive training intervention in HM patients treated with allogeneic BMT. To date, we have enrolled 43 evaluable patients, achieving 60.4% consent rate, 77.3% randomization rate, 20.7% post-randomization attrition and median intervention adherence of 83.3%. Preliminary results show an intervention effect in improved processing speed (p=0.006) among patients with baseline impairment. Cognitive function, however, is a complex phenotype involving several domains best tackled using a multi-component approach that involves both compensatory (e.g. cognitive training) and enhancement of molecular pathways (e.g. nutritional ketosis) mechanisms. Ketogenic interventions have consistently shown cognitive improvements as early as 6-8 weeks in the non-oncology space including patients with mild cognitive impairment, Alzheimer's disease and dementia. While the brain's ability to use glucose as an energy source is reduced with aging; circulating plasma ketone bodies are an effective alternative due to their water solubility and ability to cross the blood brain barrier. In addition, nutritional ketosis upregulates DNA repair pathways, enhances synaptic plasticity, and reduces inflammation. These effects on cognitive outcomes in HM survivors have not been explored. We aim to explore the feasibility of integrating exogenous ketogenic supplementation to the existing 12-week cognitive training intervention, examine intervention effects using objectively measured cognitive function, and examine the sustained effects of the multi-component intervention. The study will be conducted by a qualified multidisciplinary team of investigators with experience in intervention and cancer survivorship research at the University of Alabama at Birmingham. Our established feasibility of enrolling survivors in the cognitive training intervention provides the needed infrastructure to test these aims with the future goal of implementation of a definitive multi-component cognitive randomized clinical trial in HM survivors.

项目摘要/摘要 认知障碍是接受血液系统恶性肿瘤(HM)治疗的幸存者公认的不良结局 有或没有血液或骨髓移植(BMT)。认知障碍对幸存者的挑战 独立和重返工作的能力，除了降低他们接受复杂治疗的能力 管理计划，这与患有HM的老年人的生存结果较差有关。在一个大的 对接受骨髓移植治疗的HM患者进行的前瞻性研究发现，全球认知障碍的患病率很高(高达36%) 赤字，一直持续到3年。年龄较大、男性、文化程度和收入较低、认知储备较低 此外，血脑屏障、端粒稳态和DNA修复基因的遗传变异也与此相关 会增加认知障碍的风险。为了解决减轻认知缺陷风险的需要， 我们进行了一项研究，以检验在HM中进行为期12周的家庭认知训练干预的可行性。 接受异基因骨髓移植治疗的患者。到目前为止，我们已经招募了43名可评估的患者，获得了60.4%的同意 随机化率77.3%，随机化后磨损率20.7%，干预依从性中位数83.3%。 初步结果显示，干预在改善患者的处理速度(p=0.006)方面有效果 基线损伤。然而，认知功能是一种涉及几个领域的复杂表型。 采用包括补偿性(例如认知训练)和 增强分子途径(如营养性酮症)机制。生酮干预措施 在包括患者在内的非肿瘤领域，早在6-8周就一直显示出认知能力的改善 患有轻度认知障碍、阿尔茨海默病和痴呆症。而大脑将葡萄糖作为一种 能源随着年龄的增长而减少；循环血浆酮体是一种有效的替代方案，因为它们 水溶性和穿越血脑屏障的能力。此外，营养性酮症可上调DNA修复 途径，增强突触可塑性，并减少炎症。这些对HM认知结果的影响 幸存者还没有被探索过。我们的目标是探索整合外源生酮的可行性 对现有的为期12周的认知训练干预进行补充，利用 客观测量认知功能，考察多成分干预的持续效果。 这项研究将由一个具有干预经验的合格的多学科调查团队进行 阿拉巴马大学伯明翰分校的癌症生存研究。我们已确定的可行性 让幸存者参加认知训练干预为测试这些目标提供了必要的基础设施 HM多组分认知随机临床试验的未来目标 幸存者。