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

基本信息

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
项目类别：
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&apos 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

项目摘要

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.

抽象的儿童癌症幸存者患糖尿病的风险是其兄弟姐妹的近两倍。糖尿病是一种既定的心血管危险因素，会增加重大心脏事件的风险幸存者，这一点至关重要，因为心源性死亡是该人群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危险因素。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，幸存者在较高的情况下会经历这种疾病率高于一般人群。幸运的是，通过禁食实验室测量可以轻松诊断糖尿病前期。在一般人群中，二甲双胍药物治疗或强化生活方式干预可用于糖尿病预防计划 (DPP) 可防止进展为糖尿病。如果不进行干预，估计一般人群中，每年有 4-10% 患有糖尿病前期的成年人会患上糖尿病。然而，人们却知之甚少尽管圣裘德终身队列研究 (SJLIFE) 之前的报告称，幸存者患有糖尿病前期研究表明，多达三分之一的成年幸存者处于糖尿病前期。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-<45 岁）。此外，幸存者具有独特的、与治疗相关的血糖控制异常风险和胰岛素稳态（包括腹部放射、颅部放射、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能够预防糖尿病同样有效，并且幸存者的耐受性良好。 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医疗评估。杠杆作用通过该资源，我们的目标是试点一种适应性、开放标签的干预措施，结合以下方法来预防糖尿病：每日二甲双胍和数字化提供的生活方式改变项目针对儿童癌症成年幸存者糖尿病前期。所有参与者最初都将参加生活方式改变计划的磨合期，并增加根据实验室标准，对于仍处于糖尿病前期高风险的参与者，每日服用二甲双胍。这主要目标是提供必要的可行性数据以及功效的初步证据（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这一高危人群的相关心脏并发症。探索性目标是评估效果胰岛素敏感性、人体测量、体力活动、饮食改变、健康相关的治疗生活质量和脆弱性。