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他们的兄弟姐妹的两倍。 糖尿病是一种公认的心血管危险因素，会增加发生重大心脏事件的风险 幸存者，这一点至关重要，因为心源性死亡是这一人群晚期非癌症死亡的主要原因。 因此，糖尿病是降低心脏风险的一个主要的可改变的危险因素。此外，众所周知，糖尿病会增加 其他慢性健康状况的风险，包括慢性肾脏疾病，幸存者经历的风险较高 这一比例高于一般人口。幸运的是，通过禁食实验室测量很容易诊断出糖尿病前期。 在普通人群中，二甲双胍的药物治疗或强化的生活方式干预用于 糖尿病预防计划(DPP)可防止进展为糖尿病。在没有干预的情况下，估计 在普通人群中，每年有4%-10%的糖尿病前期成年人会患上糖尿病。然而，人们对此知之甚少 关于幸存者的糖尿病前期，尽管圣裘德终身队列研究(SJLIFE)之前的报告 表明高达三分之一的成年幸存者患有糖尿病前期。我们的初步数据表明， 儿童癌症幸存者中的糖尿病前期几乎是年轻人中同龄对照组的两倍 (18岁和45岁)。此外，幸存者有独特的与治疗相关的血糖控制异常风险和 胰岛素稳态(包括腹部辐射、头颅辐射、造血细胞移植和 皮质类固醇暴露)。因此，尚不清楚在普通人群中使用的干预措施是否会 预防糖尿病在幸存者中也同样有效，耐受性良好。SJLIFE队列现在包含 为5000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 这一资源，我们的目标是试点一种适应性的，开放标签的干预措施，以预防糖尿病使用的组合 儿童癌症成年幸存者的每日二甲双胍和数字传递的生活方式改变计划 糖尿病前期。所有参与者将首先参加生活方式改变计划的磨合期，并增加 根据实验室标准，仍处于糖尿病前期高危状态的参与者每日服用二甲双胍。这个 主要目标是提供基本的可行性数据以及有效性的初步证据(改进 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。探索性目标是评估效果 胰岛素敏感性、人体测量、体力活动、饮食变化、与健康相关的治疗 生活质量和虚弱。