An Open-Label Pilot Intervention Trial to Prevent Diabetes in Prediabetic Adult Survivors of Childhood Cancer
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 96
- 试验地点
- 1
- 主要终点
- Safety and Adverse Events (Symptom Log including monitoring for AEs)
研究概览
简要总结
This is a first-in survivor, single-arm pilot study with the goal of establishing evidence of feasibility and safety of a combined pharmacologic (metformin) and lifestyle intervention (using an existing digital platform) to prevent diabetes in prediabetic adult survivors of childhood cancer.
Primary Objective
The primary aim of this proposal is to establish the feasibility and safety of a 24-week combined metformin + intensive lifestyle intervention among adult survivors with prediabetes (including a 12-week lifestyle alone run-in followed by 12-week combined intervention among survivors remaining prediabetic).
Primary endpoints of this trial will be adherence to 1) daily metformin administration and 2) completion of required core-curriculum of the lifestyle change intervention. Safety will be assessed using the Global Rating of Side Effects Burden
Secondary Objectives
The secondary aim is to assess preliminary evidence for efficacy of the combined metformin + intensive lifestyle intervention on glycemic control and insulin resistance. Glycemic control will be measured by fasting plasma glucose (FPG) and hemoglobin A1c (HbA1c) and insulin resistance measured by the homeostatic model assessment (HOMA-IR) and IGF- binding protein 1 (IGF-BP1; a measure of insulin sensitivity strongly correlated with euglycemic insulin clamp testing).
Exploratory Objectives
To assess preliminary evidence for efficacy of the combined metformin + intensive lifestyle intervention on weight, other anthropometric measures, blood pressure and lipid profile, physical activity (self-reported and as measured by accelerometer), frailty measures, and health-related quality of life (HRQOL). We will also assess diabetes development at future SJLIFE visits.
To assess measures of participation in the lifestyle change program as well as barriers to participation and medication adherence.
详细描述
Eligible subjects who meet inclusion criteria will be enrolled in a 12 week run-in period of the digital lifestyle intervention program. At the 12 week study visit, those who remain prediabetic will received metformin extended release daily, first at lower dose (500 mg/day) to minimize gastrointestinal side effects (diarrhea, nausea, flatulence, bloating), then escalated to a maximum dose of 1000 mg/day at week 14. The digitally delivered lifestyle change program will include a core curriculum focused on diet quality, food types, exercise and behavioral strategies for goal setting, and self- monitoring.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
盲法说明
The schema was changed the to an adaptive trial design with a 12 week lifestyle run-in followed by a combined metformin+lifestyle intervention for 12 weeks
入排标准
- 年龄范围
- 18 Years 至 44 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Investigators will recruit to enroll 55 survivors who are at least 18 but <45 years of age who participate in the St. Jude Lifetime Cohort Study (SJLIFE) and have been identified to have prediabetes defined as hemoglobin A1c (HbA1c)
- •Participant in SJLIFE
- •≥18 and <45 years of age
- •Prediabetic: fasting plasma glucose 105-125 mg/dL, hemoglobin A1c 5.7- 6.4% (either or both criteria may be present) According to institutional and NIH policy, the study will accession research participants regardless of sex and ethnic background. Institutional experience confirms broad representation in this regard.
排除标准
- •Absence of treatment related diabetes risk. Survivors will be excluded if their cancer treatment required observation only, surgery alone not involving the abdomen or brain, radiation alone not involving the chest (pancreatic risk), abdomen or brain (e.g. retinoblastoma treated with enucleation alone, melanoma of an extremity treated with excision alone, neuroblastoma in an infant requiring observation only)
- •Diabetes at baseline assessment: FPG ≥126 mg/dL, HbA1c ≥6.5% or previous diagnosis by a physician (except gestational diabetes that resolved post-partum)
- •BMI <19 kg/m2
- •Current metformin use (including for any period ≥30 days in the past 1yr)
- •Known allergy to metformin
- •Current use of other oral glucose lowering medications, non-insulin injectable diabetes medications or insulin (Appendix)
- •Current participation in a lifestyle change program
- •Chronic kidney disease ≥ stage IIIb (eGFR < 45 mL/min)
- •Severe cardiovascular disease or recent intervention (NYHA class ≥2 or heart failure hospitalization in the past 6mo, Aortic stenosis, Heart block including LBBB or 3rd degree AV block, SBP >180 or DBP >105 mmHg, myocardial infarction or coronary revascularization in the past 1 month)
- •Severe hepatic dysfunction: cirrhosis or AST/ALT >3 times upper limit of normal
- •Pulmonary disease with dependence on oxygen or daily use of bronchodilators
- •Weight loss >10% in the past 6 months
- •Bariatric surgery in the past 2 years
- •Pregnant, within 3 months post-partum, nursing, or planning to become pregnant
- •Anemia: hematocrit <36% in males or <33% in females
- •Ongoing alcohol or substance abuse using criteria from the AUDIT and DAST questionnaires (Appendix)
- •Diagnosis of schizophrenia or other psychotic disorder
- •Vision impairment limiting ability to interface with the digital program
- •Unable to swallow medication
- •Non-English speaking
- •Cognitive impairment defined by IQ <80
- •Current active cancer or undergoing treatment for active cancer
研究组 & 干预措施
Treatment
Metformin is an antihyperglycemic agent which improves glucose tolerance in patients with type 2 diabetes mellitus, lowering both basal and postprandial plasma glucose. Metformin decreases hepatic glucose production, decreases intestinal absorption of glucose, and improves insulin sensitivity by increasing peripheral glucose uptake and utilization. With Metformin therapy, insulin secretion remains unchanged while fasting insulin levels and day-long plasma insulin response may decrease.
干预措施: Digital Intervention (Behavioral)
Treatment
Metformin is an antihyperglycemic agent which improves glucose tolerance in patients with type 2 diabetes mellitus, lowering both basal and postprandial plasma glucose. Metformin decreases hepatic glucose production, decreases intestinal absorption of glucose, and improves insulin sensitivity by increasing peripheral glucose uptake and utilization. With Metformin therapy, insulin secretion remains unchanged while fasting insulin levels and day-long plasma insulin response may decrease.
干预措施: Metformin (Drug)
结局指标
主要结局
Safety and Adverse Events (Symptom Log including monitoring for AEs)
时间窗: Week 24
An Adverse Event Monitoring Log with Global Rating of Side Effects Burden
Adherence for feasibility
时间窗: 2 years
Adherence to the intervention with 80% adherence to prescribed metformin and completion of 60% of the digitally-delivered core education curriculum through the lifestyle change platform.
Digitally-delivered core education curriculum through the lifestyle change platform
时间窗: At end of Week 24
Adherence will be monitored by completion logs of lessons
Drug adherence/Pill Counts
时间窗: Week 24
Adherence will be monitored by pill counts showing participant taking study drug, metformin ER, 80% of the time.
Safety and Adverse Events (Symptom Log including monitoring for AEs)
时间窗: Week 4
An Adverse Event Monitoring Log with Global Rating of Side Effects Burden
Safety and Adverse Events (Symptom Log including monitoring for AEs)
时间窗: Week 8
An Adverse Event Monitoring Log with Global Rating of Side Effects Burden
Safety and Adverse Events (Symptom Log including monitoring for AEs)
时间窗: Week 12
An Adverse Event Monitoring Log with Global Rating of Side Effects Burden
Safety and Adverse Events (Symptom Log including monitoring for AEs)
时间窗: Week 14
An Adverse Event Monitoring Log with Global Rating of Side Effects Burden
Safety and Adverse Events (Symptom Log including monitoring for AEs)
时间窗: Week 16
An Adverse Event Monitoring Log with Global Rating of Side Effects Burden
Safety and Adverse Events (Symptom Log including monitoring for AEs)
时间窗: Week 20
An Adverse Event Monitoring Log with Global Rating of Side Effects Burden
Drug adherence/Pill Counts
时间窗: Week 2
Adherence will be monitored by pill counts showing participant taking study drug, metformin ER, 80% of the time.
Drug adherence/Pill Counts
时间窗: Week 4
Adherence will be monitored by pill counts showing participant taking study drug, metformin ER, 80% of the time.
Drug adherence/Pill Counts
时间窗: Week 8
Adherence will be monitored by pill counts showing participant taking study drug, metformin ER, 80% of the time.
Drug adherence/Pill Counts
时间窗: Week 12
Adherence will be monitored by pill counts showing participant taking study drug, metformin ER, 80% of the time.
Drug adherence/Pill Counts
时间窗: Week 16
Adherence will be monitored by pill counts showing participant taking study drug, metformin ER, 80% of the time.
Drug adherence/Pill Counts
时间窗: Week 20
Adherence will be monitored by pill counts showing participant taking study drug, metformin ER, 80% of the time.
次要结局
- Glycemic Control(Baseline to Week 24 (on campus labs at Baseline, Week 12 and 24)
- Glycemic Control(Baseline to Week 24 (on campus labs at Baseline, Week 12 and 24))