PreDM: An adaptive, open-label, pilot intervention trial for diabetes prevention

PreDM：一项针对糖尿病预防的适应性、开放标签试点干预试验

• 批准号: 10457639
• 负责人: Stephanie Berry Dixon
• 金额: $ 25.08万
• 依托单位: ST. JUDE CHILDREN'S RESEARCH HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-08-01 至 2024-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10457639
• 关键词: Abdomen; Adrenal Cortex Hormones; Adult; Adverse event; Age; Age of Onset; Beta Cell; Body Composition; Body mass index; Cardiac; Cardiac Death; Cardiotoxicity; Caring; Child; Chronic; Chronic Kidney Failure; Cohort Studies; Combined Modality Therapy; Common Terminology Criteria for Adverse Events; Cranial Irradiation; Data; Development; Diabetes Mellitus; Diabetes prevention; Diagnosis; Educational Curriculum; Event; Exposure to; Fasting; Feasibility Studies; Future; General Population; Glycosylated hemoglobin A; Health; High Prevalence; Homeostasis; IGFBP1 gene; Institution; Insulin; Insulin Resistance; Intervention; Intervention Trial; Laboratories; Life Style; Long-Term Survivors; Malignant Neoplasms; Measures; Medical; Metformin; Modeling; Morbidity - disease rate; Online Systems; Participant; Pharmacology; Physical activity; Pilot Projects; Population; Prediabetes syndrome; Prevalence; Prevention strategy; Quality of life; Race; Radiation; Randomized; Randomized Clinical Trials; Reporting; Resources; Risk; Risk Factors; Risk Reduction; Running; Safety; Saint Jude Children' s Research Hospital; Siblings; Supportive care; Survivors; Treatment Efficacy; aged; base; blood glucose regulation; cancer complication; cancer therapy; cardiovascular risk factor; cell injury; childhood cancer survivor; cohort; diabetes prevention program; diabetes risk; diabetic; dietary; digital; early onset; efficacy clinical trial; efficacy trial; exercise intervention; experience; fasting plasma glucose; frailty; glycemic control; health related quality of life; hematopoietic cell transplantation; high risk; high risk population; improved; individualized medicine; insulin sensitivity; lifestyle intervention; modifiable risk; mortality; open label; prevent; primary endpoint; programs; safety and feasibility; secondary endpoint; sex; treatment adherence; treatment effect; young adult

ABSTRACT Childhood cancer survivors have nearly twice the risk for developing diabetes compared to their siblings. Diabetes is an established cardiovascular risk factor potentiating the risk for major cardiac events among survivors, which is critical as cardiac death is the leading cause of non-cancer late mortality in this population. Thus, diabetes is a major modifiable risk factor for cardiac risk reduction. Further, diabetes is known to increase risk for other chronic health conditions, including chronic kidney disease, which survivors experience at higher rates than the general population. Fortunately, prediabetes is easily diagnosed by fasting laboratory measures. In the general population, pharmacologic therapy with metformin or intensive lifestyle intervention used in the Diabetes Prevention Program (DPP) prevents progression to diabetes. Without intervention, it is estimated that 4-10% of adults with prediabetes in the general population will become diabetic each year. Yet, little is known about prediabetes in survivors despite previous reports from the St. Jude Lifetime Cohort Study (SJLIFE) that suggest up to one-third of adult survivors are prediabetic. Our preliminary data suggests that the prevalence of prediabetes among childhood cancer survivors is near twice that of similarly aged controls among young adults (18-<45 years). Further, survivors have unique, treatment-related risk for abnormalities in glucose control and insulin homeostasis (including abdominal radiation, cranial radiation, hematopoietic cell transplant and corticosteroid exposure). Therefore, it is unknown if interventions that are used in the general population to prevent diabetes will be similarly efficacious and well tolerated among survivors. The SJLIFE cohort now contains comprehensive treatment information and direct medical assessments for over 5,000 adult survivors. Leveraging this resource, we aim to pilot an adaptive, open-label intervention to prevent diabetes using a combination of daily metformin and a digitally-delivered lifestyle change program among adult survivors of childhood cancer with prediabetes. All participants will initially take part in a lifestyle change program run-in period with the addition of daily metformin among participants who remain at high-risk for prediabetes based on laboratory criteria. The primary objective is to provide essential feasibility data as well as preliminary evidence for efficacy (improved glycemic control and/or insulin resistance) for a future randomized intervention trial for prevention of diabetes and associated cardiac complications in this high-risk population. Exploratory objectives are to evaluate the effect of treatment on insulin sensitivity, anthropometric measures, physical activity, dietary change, health-related quality of life and frailty.

摘要 儿童癌症幸存者患糖尿病的风险几乎是其兄弟姐妹的两倍。 糖尿病是一种确定的心血管危险因素， 幸存者，这是至关重要的，因为心源性死亡是该人群中非癌症晚期死亡的主要原因。 因此，糖尿病是降低心脏病风险的主要可改变风险因素。此外，已知糖尿病会增加 其他慢性健康状况的风险，包括慢性肾病，幸存者在较高的 比一般人口。幸运的是，糖尿病前期很容易通过空腹实验室测量进行诊断。 在一般人群中，二甲双胍药物治疗或强化生活方式干预用于 糖尿病预防计划（DPP）可预防糖尿病进展。如果不进行干预，估计 在一般人群中，每年有4-10%的糖尿病前期成年人将成为糖尿病患者。然而， 尽管之前圣犹达终身队列研究（SJLIFE）的报告显示， 表明多达三分之一成年幸存者是前驱糖尿病。我们的初步数据表明， 儿童癌症幸存者中的前驱糖尿病几乎是年轻成年人中年龄相似的对照组的两倍 (18-45岁）。此外，存活者具有独特的治疗相关的血糖控制异常风险， 胰岛素稳态（包括腹部放射、颅骨放射、造血细胞移植和 皮质类固醇暴露）。因此，尚不清楚在一般人群中使用的干预措施是否 预防糖尿病的药物在幸存者中同样有效且耐受良好。SJLIFE队列现在包含 为5 000多名成年幸存者提供全面的治疗信息和直接的医疗评估。利用 我们的目标是试验一种适应性的、开放标签的干预措施，以预防糖尿病， 每日二甲双胍和数字化生活方式改变计划在儿童癌症成年幸存者中的应用 糖尿病前期所有参与者最初将参加一个生活方式改变计划的磨合期， 根据实验室标准，在糖尿病前期高危受试者中每日二甲双胍。的 主要目的是提供必要的可行性数据以及疗效的初步证据（改善 血糖控制和/或胰岛素抵抗）用于未来预防糖尿病的随机干预试验 以及相关的心脏并发症。探索性目的是评估 胰岛素敏感性、人体测量、体力活动、饮食改变、健康相关 生活质量和脆弱性。