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：
10668457
负责人：
Stephanie Berry Dixon
金额：
$ 20.82万
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/10668457
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 Physical activity Pilot Projects Population Prediabetes syndrome Prevalence Prevention strategy Quality of life Race Radiation Randomized Reporting Resources Risk Risk Factors Risk Reduction Running Safety Saint Jude Children&apos s Research Hospital Siblings Supportive care Survivors Treatment Efficacy aged blood glucose regulation cancer complication cancer therapy cardiovascular risk factor cell injury childhood cancer survivor cohort diabetes prevention program diabetes risk diabetic dietary digital delivery digital platform 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 insulin sensitivity lifestyle intervention modifiable risk mortality open label pharmacologic prevent primary endpoint programs progression risk randomized, clinical trials safety and feasibility secondary endpoint sex treatment adherence treatment effect young adult

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 Physical activity Pilot Projects Population Prediabetes syndrome Prevalence Prevention strategy Quality of life Race Radiation Randomized Reporting Resources Risk Risk Factors Risk Reduction Running Safety Saint Jude Children&apos s Research Hospital Siblings Supportive care Survivors Treatment Efficacy aged blood glucose regulation cancer complication cancer therapy cardiovascular risk factor cell injury childhood cancer survivor cohort diabetes prevention program diabetes risk diabetic dietary digital delivery digital platform 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 insulin sensitivity lifestyle intervention modifiable risk mortality open label pharmacologic prevent primary endpoint programs progression risk randomized, clinical trials safety and feasibility secondary endpoint sex treatment adherence treatment effect young adult

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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.

抽象的与兄弟姐妹相比，儿童癌症幸存者的糖尿病风险几乎是患糖尿病的两倍。糖尿病是一种既定的心血管危险因素，增强了发生重大心脏事件风险幸存者，这是至关重要的，因为心脏死亡是该人群中非癌症晚期死亡率的主要原因。因此，糖尿病是降低心脏风险的主要风险因素。此外，已知糖尿病会增加其他慢性健康状况的风险，包括慢性肾脏疾病，幸存者在较高的比率比一般人口。幸运的是，禁食实验室措施很容易诊断前糖尿病。在一般人群中，使用二甲双胍或强化生活方式干预的药理学治疗糖尿病预防计划（DPP）可以防止糖尿病发展。没有干预，据估计普通人群中糖尿病前期的成年人中有4-10％每年都会成为糖尿病。但是，知之甚少关于幸存者的前糖尿病，尽管圣裘德终身队列研究（SJLife）以前的报道说建议多达三分之一的成年幸存者是糖尿病前期。我们的初步数据表明儿童癌症幸存者之间的糖尿病是年轻人的两倍（18- <45岁）。此外，幸存者在葡萄糖控制和胰岛素稳态（包括腹部辐射，颅辐射，造血细胞移植和皮质类固醇暴露）。因此，尚不清楚一般人群中使用的干预措施是否预防糖尿病将同样有效，并且在幸存者中耐受性良好。 SJLife队列现在包含 5,000多名成人幸存者的全面治疗信息和直接的医疗评估。利用我们旨在尝试进行自适应的开放标签干预措施，以防止糖尿病每日二甲双胍和儿童癌症幸存者的数字化生活方式改变计划糖尿病。所有参与者最初都会参加生活方式改变计划的跑步期，并增加根据实验室标准，参与者的每日二甲双胍。这主要目的是提供必要的可行性数据以及有效性的初步证据（提高了血糖控制和/或胰岛素抵抗）用于预防糖尿病的未来随机干预试验以及这种高危人群中的相关心脏并发症。探索性目标是评估效果胰岛素敏感性，人体测量指标，体育锻炼，饮食变化，与健康有关的治疗生活质量和脆弱。