Restoring Insulin Secretion Pediatric Medication Study
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 91
- 试验地点
- 4
- 主要终点
- ß-cell Response Measured by Hyperglycemic Clamp
研究概览
简要总结
The RISE Pediatric Medication Study is a 2-arm, 4-center, clinical trial of children with prediabetes and early type 2 diabetes to address the hypothesis that aggressive glucose lowering will lead to recovery of beta-cell function that will be sustained after withdrawal of treatment. Pediatric participants (ages 10-19) will be randomized to one of the following treatment regimens: (1) metformin alone or (2) early intensive treatment with basal insulin glargine followed by metformin.
The primary clinical question RISE will address is: Are improvements in ß-cell function following 12 months of active treatment maintained for 3 months following the withdrawal of therapy? Secondary outcomes will assess durability of glucose tolerance following withdrawal of therapy, and whether biomarkers obtained in the fasting state predict parameters of ß-cell function, insulin sensitivity and glucose tolerance and the response to an intervention.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 10 Years 至 19 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Fasting plasma glucose ≥90 mg/dl plus 2-hour glucose ≥140 mg/dl on 75 gm OGTT plus laboratory-based HbA1c ≤8.0% if treatment naïve. There is no upper limit for the 2-hour glucose on OGTT. In those taking metformin laboratory-based HbA1c must be ≤7.5% if on metformin for <3 months and ≤7.0% if on metformin for 3-6 months.
- •Age 10-19 years
- •Pubertal development Tanner stage >1 as defined by breast stage >1 in girls, and testes >3 cc's in boys.
- •Body mass index (BMI) ≥85th percentile but ≤50 kg/m2
- •Self-reported diabetes <6 months in duration
- •Treatment with metformin for <6 months preceding screening
排除标准
- •Underlying disease likely to limit life span and/or increase risk of intervention or an underlying condition that is likely to limit ability to participate in outcomes assessment
- •An underlying disease that affects glucose metabolism other than type 2 diabetes mellitus
- •Taking medications that affect glucose metabolism, or has an underlying condition that is likely to require such medications
- •Treatment with insulin for >1 week preceding screening
- •Active infections
- •Renal disease (serum creatinine >1.2 mg/dl) or serum potassium abnormality (<3.4 or >5.5 mmol/l)
- •Anemia (hemoglobin <11 g/dl in girls, <12 g/dl in boys) or known coagulopathy
- •Cardiovascular disease, including uncontrolled hypertension defined as average systolic or diastolic blood pressure > 99 percentile for age or >135/90, despite adequately prescribed antihypertensive medications. Participants must be able to safely tolerate administration of intravenous fluids required during clamp studies.
- •History of conditions that may be precipitated or exacerbated by a study drug:
- •Serum alanine transaminase (ALT) more than 3 times the upper limit of normal
- •Excessive alcohol intake
- •Sub-optimally treated thyroid disease
- •Conditions or behaviors likely to affect the conduct of the RISE Study
- •Participant and/or parents unable or unwilling to give informed consent
- •Participant and/or parents unable to adequately communicate with clinic staff
- •Another household member is a participant or staff member in RISE
- •Current, recent or anticipated participation in another intervention research project that would interfere with any of the interventions/outcomes in RISE
- •Weight loss of ≥5% of body weight in the past 3 months for any reason other than post-partum weight loss. Participants taking weight loss drugs or using preparations taken for intended weight loss are excluded.
- •Likely to move away from participating clinics in next 2 years
- •Current (or anticipated) pregnancy and lactation.
- •A pregnancy that was completed less than 6 months prior to screening.
- •Breast feeding within 6 months prior to screening.
- •Women of childbearing potential who are unwilling to use adequate contraception
- •Major psychiatric disorder that, in the opinion of clinic staff, would impede the conduct of RISE
- •Additional conditions may serve as criteria for exclusion at the discretion of the local site.
研究组 & 干预措施
Metformin alone
Metformin will be titrated to the maximum dose tolerated (up to 2000 mg/day).
干预措施: Metformin (Drug)
Glargine followed by Metformin
Basal insulin glargine for 3 months titrated to achieve a morning fasting blood glucose of 85-95 mg/dl, followed by metformin (titrated up to 2000 mg/day) for 9 months.
干预措施: Metformin (Drug)
Glargine followed by Metformin
Basal insulin glargine for 3 months titrated to achieve a morning fasting blood glucose of 85-95 mg/dl, followed by metformin (titrated up to 2000 mg/day) for 9 months.
干预措施: Glargine (Drug)
结局指标
主要结局
ß-cell Response Measured by Hyperglycemic Clamp
时间窗: 3-months after medication washout (Month 15)
Clamp measures of ß-cell response, co-primary outcomes
M/I
时间窗: 3-months after a medication washout
Clamp measure of insulin sensitivity
次要结局
- ACPRg(3-months after a medication washout)
- ß-cell Function Measured by Hyperglycemic Clamp Techniques at M12(End of active intervention (Month 12).)
- Clamp Measure of Insulin Sensitivity(End of active intervention (Month 12))