Restoring Insulin Secretion Adult Medication Study
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 267
- 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 Adult Medication Study is a 4-arm, 3-center, clinical trial of adults 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. Adult participants (ages 20-65) will be randomized to one of the following treatment regimens: (1) blinded placebo, (2) blinded metformin alone, (3) early intensive insulin treatment with basal insulin glargine followed by open-label metformin, (4) the glucagon-like peptide-1 receptor agonist (GLP-1RA) liraglutide plus open-label 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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 20 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Fasting plasma glucose 95-125 mg/dl plus 2-hour glucose ≥140 mg/dl on 75 gm OGTT plus HbA1c ≤7.0%. There is no upper limit for the 2-hour glucose on OGTT.
- •Age 20-65 years
- •Body mass index (BMI) ≥25 kg/m2 but ≤50 kg/m2
- •Self-reported diabetes <1 year in duration
- •Drug naïve (no prior to oral glucose lowering agent(s), insulin or other injectable glucose lowering agents)
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
- •Taking medications that affect glucose metabolism, or has an underlying condition that is likely to require such medications
- •Active infections
- •Renal disease (serum creatinine >1.4 mg/dl for men; >1.3 mg/dl for women) or serum potassium abnormality (<3.4 or >5.5 mmol/l)
- •Anemia (hemoglobin <11 g/dl in women, <12 g/dl in men) or known coagulopathy
- •Cardiovascular disease, including uncontrolled hypertension. 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:
- •Pancreatitis
- •Serum alanine transaminase (ALT) more than 3 times the upper limit of normal
- •Excessive alcohol intake
- •Suboptimally treated thyroid disease
- •Medullary carcinoma of the thyroid or MEN-2 (in participant or a family history)
- •Hypertriglyceridemia (>400 mg/dl despite treatment)
- •Conditions or behaviors likely to affect the conduct of the RISE Study
- •Unable or unwilling to give informed consent
- •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% in past three 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 two years
- •Women of childbearing potential who are unwilling to use adequate contraception
- •Current (or anticipated) pregnancy and lactation.
- •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). Participants randomized to the metformin-alone arm will be blinded to treatment.
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 80-90 mg/dl, followed by open-label 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 80-90 mg/dl, followed by open-label metformin (titrated up to 2000 mg/day) for 9 months.
干预措施: Glargine (Drug)
Placebo
Placebo - masked to metformin-alone. Placebo will be titrated to the maximum number of tablets equivalent to maximum dose of metformin.
干预措施: Placebo (Drug)
Liraglutide + Metformin
Liraglutide + open-label Metformin. Liraglutide will be titrated to the maximum dose tolerated (up to 1.8 mg/day) after which metformin will be titrated to the maximum dose tolerated (up to 2000 mg/day).
干预措施: Metformin (Drug)
Liraglutide + Metformin
Liraglutide + open-label Metformin. Liraglutide will be titrated to the maximum dose tolerated (up to 1.8 mg/day) after which metformin will be titrated to the maximum dose tolerated (up to 2000 mg/day).
干预措施: Liraglutide (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
Insulin Sensitivity, 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(Secondary analysis was on all participants with a Month 12 visit.)