Preserving Beta-cell Function in Type 2 Diabetes With Exenatide and Insulin (PREVAIL)
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 105
- 试验地点
- 1
- 主要终点
- Mean beta-cell function over the 8-week treatment period, measured using the Insulin Secretion-Sensitivity Index-2 (ISSI-2)
研究概览
简要总结
Type 2 diabetes mellitus is a chronic metabolic disorder characterized by progressive deterioration in the function of the pancreatic beta-cells, which are the cells that produce and secrete insulin (the hormone primarily responsible for the handling of glucose in the body). The investigators propose a randomized controlled trial to determine whether combining basal insulin with a new medication called exenatide is a therapeutic strategy that can preserve beta-cell function early in the course of type 2 diabetes.
详细描述
In this open-label, parallel-arm randomized controlled trial, adults with T2DM of ≤7 years duration on 0-2 anti-diabetic medications will be randomized to 8-weeks treatment with either (i) basal insulin glargine, (ii) intensive insulin therapy consisting of glargine and pre-meal insulin lispro, or (iii) glargine and the GLP-1 agonist exenatide (twice daily). They will then go into a 12-week washout on lifestyle modification only. Beta-cell function will be assessed by determining the Insulin Secretion-Sensitivity Index-2 (ISSI-2) on oral glucose tolerance test (OGTT) performed at baseline, 4-weeks, 8-weeks, and 20-weeks. The primary outcome will be mean beta-cell function (ISSI-2) over the 8-week treatment period.
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
- 30 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Men and women between the ages of 30 and 80 years inclusive
- •T2DM diagnosed by a physician ≤7 years prior to enrolment
- •On 0-2 anti-diabetic medications, with no change in dose/regimen in the preceding 4 weeks
- •A1c at screening between 5.5% and 9.0% inclusive if on anti-diabetic medications, or between 6.0% and 9.5% inclusive if on no oral anti-diabetic medication
- •BMI ≥ 23 kg/m2
- •Negative pregnancy test at recruitment for all women with childbearing potential
排除标准
- •Current anti-diabetic treatment with insulin or a glucagon-like peptide-1 (GLP-1) agonist
- •Type 1 diabetes or secondary forms of diabetes
- •History of hypoglycemia unawareness or severe hypoglycemia requiring assistance
- •Hypersensitivity to insulin, exenatide, or the formulations of these products
- •Renal dysfunction as evidenced by estimated glomerular filtration rate (eGFR)<30 ml/min by Modification of Diet in Renal Disease (MDRD) formula
- •History of pancreatitis
- •Family or personal history of Multiple Endocrine Neoplasia type 2 (MEN-2) or familial medullary thyroid carcinoma (MTC)
- •Personal history of non-familial medullary thyroid carcinoma (MTC)
- •Malignant neoplasm requiring chemotherapy, surgery, radiation or palliative therapy within the previous 5 years (with the exception of basal cell skin cancer)
- •Unwillingness to perform capillary glucose monitoring at least 4 times a day during treatment
- •Pregnancy or unwillingness to use reliable contraception. Women should not be planning pregnancy for the duration of the study or the first 3 months after the study. Reliable contraception includes birth control pill, intra-uterine device, abstinence, tubal ligation, partner vasectomy, or condoms with spermicide.
- •Any factor likely to limit adherence to the protocol, in the opinion of investigator
研究组 & 干预措施
Basal insulin and exenatide
Participants in this arm will undergo an 8-week course of treatment with exenatide and insulin glargine. Exenatide will be initiated at 5ug subcutaneous (sc) bid (before breakfast and before dinner) for the first 4 weeks, followed by 10ug bid for the next 4 weeks. Glargine sc injection at bedtime will be titrated to fasting glucose.
干预措施: Basal insulin and exenatide (Drug)
Basal insulin only
Participants in this arm will undergo an 8-week course of treatment with glargine sc injection at bedtime, titrated to target fasting glucose.
干预措施: Basal insulin only (Drug)
Basal Insulin and bolus insulin
Participants in this arm will undergo an 8-week course of multiple daily insulin injection therapy, consisting of titrated basal insulin glargine at bedtime and insulin lispro before each meal.
干预措施: Basal insulin and bolus insulin (Drug)
结局指标
主要结局
Mean beta-cell function over the 8-week treatment period, measured using the Insulin Secretion-Sensitivity Index-2 (ISSI-2)
时间窗: 8 weeks
ISSI-2 is an established measure of beta-cell function. ISSI-2 is defined as the product of (i) insulin secretion measured by the ratio of the area-under-the-insulin-curve to the area-under-the-glucose curve and (ii) insulin sensitivity measured by the Matsuda index. The primary outcome comparison is between the glargine/exenatide and glargine only arms.
次要结局
- Baseline-adjusted beta-cell function at 20 weeks(20 weeks)
- Endothelial function at 8 weeks(8 weeks)
- Baseline-adjusted glycemic control at 8 weeks(8 weeks)
- Baseline-adjusted glycemic control at 20 weeks(20 weeks)