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

基本信息

批准号：
10626850
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
项目类别：
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/10626850
关键词：
Address Adherence Affect Aging Alabama Allogenic Alzheimer&apos s Disease Appointment Area Attention 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 Dementia 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 Ketoses Ketosis Learning Malignant Neoplasms Measures Memory Metabolic Metabolic Pathway Molecular Morbidity - disease rate Nutritional Outcome Pathway interactions Patients Pharmaceutical Preparations Phenotype Pilot Projects Plasma Population Prospective Studies Qualifying Quality of life Randomized Research Research Personnel Risk Self Management Short-Term Memory Standardization Supplementation Survivors Synaptic plasticity Testing Transplant Recipients Treatment Efficacy Universities Waiting Lists Work adverse outcome arm blood-brain barrier crossing cancer therapy cellular targeting cognitive function cognitive reserve cognitive testing cognitive training comparison intervention computerized efficacy evaluation executive function experience future implementation genetic variant high risk human old age (65+)improved interest intervention effect intervention program ketogentic longitudinal, prospective study male mild cognitive impairment mortality multi-component intervention multidisciplinary novel phase III trial processing speed programs randomized, clinical trials risk mitigation sex survival outcome telomere treatment arm treatment effect trial design water solubility

项目摘要

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.

项目概要/摘要认知障碍是血液恶性肿瘤 (HM) 治疗幸存者的一种公认的不良后果无论是否进行血液或骨髓移植（BMT），认知障碍都会给幸存者带来很大的挑战。独立性和重返工作岗位的能力，以及降低他们接受复杂治疗的能力管理计划与 HM 老年人较差的生存结果相关。对接受 BMT 治疗的 HM 患者进行的前瞻性研究发现，整体认知能力的患病率很高（高达 36%）缺陷，持续至年龄较大、男性、教育程度和收入较低、认知储备较低等。以及血脑屏障、端粒稳态和 DNA 修复基因的遗传变异相关认知障碍的风险增加为了满足减轻认知缺陷风险的需要，我们进行了一项研究，旨在检验 HM 进行为期 12 周的家庭认知训练干预的可行性迄今为止，我们已招募了 43 名可评估患者，获得了 60.4% 的同意。率，77.3% 的随机化率，20.7% 的随机化后流失率，中位干预依从性为 83.3%。初步结果显示，干预对患有以下疾病的患者的处理速度有改善作用（p=0.006）：然而，认知功能是一种复杂的表型，涉及多个领域。使用多成分方法来解决，涉及补偿（例如认知训练）和分子途径（例如营养酮症）机制的增强具有生酮干预作用。在非肿瘤领域（包括患者），认知能力早在 6-8 周就得到了持续改善患有轻度认知障碍、阿尔茨海默病和痴呆症，而大脑利用葡萄糖的能力。能量来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品，因为它们具有水溶性和穿过血脑屏障的能力此外，营养酮症可上调 DNA 修复。途径，增强突触可塑性，并减少炎症对 HM 认知结果的影响。我们的目的是探索整合外源生酮的可行性。作为现有 12 周认知训练干预的补充，使用以下方法检查干预效果：客观测量认知功能，并检查多成分干预的持续效果。该研究将由具有干预经验的合格的多学科研究人员团队进行和伯明翰阿拉巴马大学癌症生存研究的可行性。让幸存者参加认知训练干预提供了测试这些目标所需的基础设施未来目标是在 HM 中实施明确的多成分认知随机临床试验幸存者。