Insulin Regulation of Lipolysis and Lipolysis Proteins
试验速览
- 阶段
- 早期 1 期
- 状态
- 招募中
- 发起方
- Mayo Clinic
- 入组人数
- 64
- 试验地点
- 2
- 主要终点
- Adipocyte response to insulin - perilipin 1 and FSP27 relative to HSL and ATGL
研究概览
简要总结
These studies will define the abnormalities in the adipocyte proteins that are involved in the failure of insulin to suppress lipolysis normally in humans with upper body obesity and will help discover the mechanism by which pioglitazone, a medication used to treat type 2 diabetes and improve insulin resistance, improves insulin-regulation of adipocyte fatty acid metabolism.
详细描述
- The investigators will determine whether impaired insulin-induced suppression of lipolysis (as measured by IC50) is related to the above mentioned lipolysis proteins in groups of volunteers known to vary widely with regards to abdominal adipocyte size and regulation of adipose tissue lipolysis.
- The investigators will determine whether the improved insulin regulation of lipolysis resulting from treatment with the PPARγ agonist pioglitazone, with or without weight loss, can be linked to specific changes in sets of PPARγ-responsive adipocyte lipolysis proteins in UBO adults.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Basic Science
- 盲法
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 18 Years 至 55 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Men and Women between the ages of 18 and
- •Women will be premenopausal
- •Non obese adults BMI between 18-25
- •Obese BMI 30-38
排除标准
- •, Pioglitazone package insert of contraindications for use:
- •Initiation in patients with established New York Heart Associations (NYHA) class III or IV Heart failure.
- •Use in patients with known hypersensitivity to pioglitazone or any other component of ACTOSE.
研究组 & 干预措施
Immediate weight loss - placebo
Upper body obese participants randomized to this group; all will begin their immediate participation in a comprehensive lifestyle obesity treatment program after completion of baseline studies. Half of the volunteers will be randomized to placebo during this period.
干预措施: Immediate weight loss (Behavioral)
Immediate weight loss - placebo
Upper body obese participants randomized to this group; all will begin their immediate participation in a comprehensive lifestyle obesity treatment program after completion of baseline studies. Half of the volunteers will be randomized to placebo during this period.
干预措施: Placebo (Drug)
Deferred control group - placebo
After baseline studies, UBO participants randomized to this group will wait without any intervention for 4 months, with continued monitoring to assure weight stability - this group will be the half of volunteers randomized to deferred weight loss intervention that are also randomized to placebo. At the end of this 'wait' period they will be enrolled in the same comprehensive lifestyle obesity treatment program for 4 months, but without placebo.
干预措施: Deferred weight loss (Behavioral)
Deferred control group - placebo
After baseline studies, UBO participants randomized to this group will wait without any intervention for 4 months, with continued monitoring to assure weight stability - this group will be the half of volunteers randomized to deferred weight loss intervention that are also randomized to placebo. At the end of this 'wait' period they will be enrolled in the same comprehensive lifestyle obesity treatment program for 4 months, but without placebo.
干预措施: Placebo (Drug)
Immediate weight loss - pioglitazone
Upper body obese participants randomized to this group; all will begin their immediate participation in a comprehensive lifestyle obesity treatment program after completion of baseline studies. Half of the volunteers will be randomized to pioglitazone during this period.
干预措施: Immediate weight loss (Behavioral)
Deferred group - pioglitazone
After baseline studies, UBO participants randomized to this group will wait without any intervention for 4 months, with continued monitoring to assure weight stability - this group will be the half of volunteers randomized to deferred weight loss intervention that are randomized to pioglitazone. They will be monitored to prevent the usual but modest weight gain associated with pioglitazone. They will be on pioglitazone during the 'wait' period.
At the end of this 'wait' period they will be enrolled in the same comprehensive lifestyle obesity treatment program for 4 months, but without pioglitazone.
干预措施: Deferred weight loss (Behavioral)
Deferred group - pioglitazone
After baseline studies, UBO participants randomized to this group will wait without any intervention for 4 months, with continued monitoring to assure weight stability - this group will be the half of volunteers randomized to deferred weight loss intervention that are randomized to pioglitazone. They will be monitored to prevent the usual but modest weight gain associated with pioglitazone. They will be on pioglitazone during the 'wait' period.
At the end of this 'wait' period they will be enrolled in the same comprehensive lifestyle obesity treatment program for 4 months, but without pioglitazone.
干预措施: Pioglitazone (Drug)
Immediate weight loss - pioglitazone
Upper body obese participants randomized to this group; all will begin their immediate participation in a comprehensive lifestyle obesity treatment program after completion of baseline studies. Half of the volunteers will be randomized to pioglitazone during this period.
干预措施: Pioglitazone (Drug)
结局指标
主要结局
Adipocyte response to insulin - perilipin 1 and FSP27 relative to HSL and ATGL
时间窗: 4-9 months
In response to weight maintenance vs. weight loss with pioglitazone vs. placebo, insulin regulation of lipolysis in upper body obese as measured by insulin IC50 for palmitate flux and compared to adipocyte perilipin 1 and FSP27 relative to HSL and ATGL.
Adipocyte response to insulin - adipocyte G0S2 relative to ATGL.
时间窗: 4-9 months
In response to weight maintenance vs. weight loss with pioglitazone vs. placebo, insulin regulation of lipolysis in upper body obese as measured by insulin IC50 for palmitate flux and compared to adipocyte G0S2 relative to ATGL.
Adipocyte response to insulin - perilipin 1, ATGL and HSL phosphorylation
时间窗: 4-9 months
In response to weight maintenance vs. weight loss with pioglitazone vs. placebo, insulin regulation of lipolysis in upper body obese as measured by insulin IC50 for palmitate flux and compared to adipocyte perilipin 1, ATGL and HSL phosphorylation in response to insulin.
Adipocyte response to insulin - adipocyte CGI-58 relative to ATGL
时间窗: 4-9 months
In response to weight maintenance vs. weight loss with pioglitazone vs. placebo, insulin regulation of lipolysis in upper body obese as measured by insulin IC50 for palmitate flux and compared to adipocyte CGI-58 relative to ATGL.
次要结局
未报告次要终点
研究者
Michael D. Jensen
Principal Investigator
Mayo Clinic