Effects of Liraglutide on Endoplasmic (ER) Stress in Obese Patients With Type 2 Diabetes
试验速览
- 阶段
- 4 期
- 入组人数
- 12
- 试验地点
- 1
- 主要终点
- Changes in unfolded protein response markers
研究概览
简要总结
The main objective of the study will be to test the hypothesis that treatment with Liraglutide will decrease ER stress and adipose tissue in obese patients with type 2 diabetes. Experimental Approach: The investigators will use a prospective, single blind, placebo controlled study design to study 12 obese patients with type 2 diabetes mellitus (T2DM). 6 patients will first receive Liraglutide for 24 weeks followed by placebo for 12 weeks. The other 6 patients will first receive placebo for 12 weeks followed by Liraglutide for 24 weeks.
Measurements: The investigators will determine glycemic control (with HbA1c), body composition (bioelectric impedance analysis), insulin sensitivity (with hyperinsulinemic-euglycemic clamps), insulin secretion (with oral glucose tolerance testing), energy balance (calories in vs. calories out), plasma lipid levels and obtain subcutaneous fat biopsies to determine ER stress response markers before and after placebo and before and after Liraglutide treatment.
详细描述
This will be a prospective, single-blind, placebo-controlled study with a crossover design.
Visit Procedures: After a 1 month run-in period during which there will be no changes in medications, physical activity or diet, patients will be randomly divided into 2 groups of 6 patients each. Subjects have a 50:50 chance of being randomized to either group 1 or group 2.
In Group 1, (n=6), liraglutide will be started first with 0.6 mg/d for 1 week, then increased to 1.2 mg/d from week 2 to week 12, followed by 1.8 mg/d from week 12 to week 24. Group 1 patients will then be switched from liraglutide to placebo injections for another 12 weeks. For subjects in Group 1 the placebo period (weeks 24 to 36 will be the washout period.
Group 2 patients (n=6) will be started with placebo for 12 weeks and then switched to liraglutide for the next 24 weeks (0.6 mg/d for 1 week, 1.2 mg/d for 11 weeks and 1.8 mg/d for 12 weeks).
Assessment of Efficacy
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Other
- 盲法
- Single (Participant)
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients with established type 2 diabetes, BMI 27-35, Age - 18-75 years, HbA1c 7-10%, patients treated with exercise, diet, metformin and/or alpha glucosidase inhibitors (all up to ½ of their maximal dose) or pioglitazone (up to 30 mg/d), ability to provide informed consent before any trial-related activities.
排除标准
- •Patients with pancreatitis or a history of pancreatitis, patients with HbA1c < 7% or > 10%, type 2 diabetic patients treated with insulin, sulfonylureas, meglitinides, dipeptidyl peptidase-4 (DPP4) inhibitors, glucagon-like peptide-1 (GLP1) agonists or corticosteroids, patients with hypoglycemia unawareness and with impaired liver functions (≥ 2.5 times the upper normal limit), known or suspected allergy against liraglutide or contraindications to liraglutide (as specified in the product prescribing information), pregnancies, breastfeeding or intention of becoming pregnant or not using adequate contraceptive measures, patients with a personal or family history of medullary thyroid cancer and patients with Multiple Endocrine Neoplasia type 2.
研究组 & 干预措施
Liraglutide
Liraglutide will be started first with 0.6 mg/d for 1 week, then increased to 1.2 mg/d from week 2 to week 12, followed by 1.8 mg/d from week 12 to week 24.
干预措施: Liraglutide (Drug)
Placebo
Subjects will receive placebo for 12 weeks.
干预措施: Liraglutide (Drug)
结局指标
主要结局
Changes in unfolded protein response markers
时间窗: baseline, 6 months, 9 months
Changes in unfolded protein response markers in adipose tissue biopsy samples. Specifically, the investigators will determine changes in mRNA (by RT-PCR) and protein (by Western blots) levels of the following ER stress markers: GRP78, ATF4, XBP-1s, PDI, calreticulin and calnexin.
次要结局
- Glucose control(baseline, 1 month, 2 months, 3 months, 4 months, 5 months, 6 months, 7 months, 8 months, 9 months)
- Body composition(baseline, 3 months, 6 months and 9 months)
- Beta cell function(baseline, 6 months, 9 months)
- Body weight(baseline, 1 month, 2 months, 3 months, 4 months, 5 months, 6 months, 7 months, 8 months, 9 months)
- Insulin sensitivity(baseline, 3 months, 6 months and 9 months)
- Energy expenditure(baseline, 3 months, 6 months, 9 months)