Short Term Effects of Leptin Withdrawal or Initiation in Lipodystrophy Independent of Energy Intake
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 25
- 试验地点
- 2
- 主要终点
- Total Body Insulin Sensitivity
研究概览
简要总结
Background:
- Lipodystrophy is a condition where people do not have enough fat in the body. People with lipodystrophy can have problems such as diabetes or an enlarged liver. Researchers are looking at how leptin, a hormone produced by fat cells, can help people with these problems. Leptin helps control appetite and how the body stores food. Taking leptin can help people with lipodystrophy eat less food, which may help treat diabetes and other problems. To better understand how leptin works, researchers want to do an inpatient study on leptin treatment in people with lipodystrophy.
Objectives:
- To study how leptin treatment affects lipodystrophy.
Eligibility:
- Individuals between 14 and 70 years of age who have lipodystrophy.
Design:
- All participants will have a 19-day stay at the National Institutes of Health Clinical Center. One group of participants will have tests for 5 days before starting to take leptin. They will then take leptin for 2 weeks, and have more tests. The other group of participants will have tests for 5 days while taking leptin. They will then take stop taking leptin for 2 weeks, and have more tests, and then they will start taking leptin again.
- Participants will have regular blood and urine tests during the visit. Some of the blood tests will look at insulin levels. Some will look at how the body metabolizes sugar and fat. Other tests will check hormone levels, especially of reproductive hormones.
- During the visit, participants will spend 3 separate days in a metabolic chamber, a special room that measures how many calories the body uses. Urine samples will be collected during these stays.
- Participants will also have several body imaging studies, including magnetic resonance imaging and a body composition scan.
- Physical activity will be tested with an exercise bicycle and an electronic activity monitor.
- Participants will be asked questions about hunger and comfort levels throughout the stay.
详细描述
Background
Leptin is an adipocyte-derived hormone that can be thought of as a signal from adipose tissue to the rest of the body conveying information about long-term nutritional status. Patients with lipodystrophy have leptin deficiency secondary to lack of adipose tissue, and thus represent a natural model for studying the effects of leptin deficiency and replacement in humans. Leptin replacement in lipodystrophy ameliorates metabolic and endocrine abnormalities, including reducing food intake, improving insulin resistance and diabetes, reducing ectopic lipid, and normalizing reproduction. The reduction in energy intake induced by leptin replacement is likely responsible for part of the improvements observed in glucose and lipid metabolism. The clinical effects of leptin that are independent of changes in energy intake, and the mechanisms underlying these effects, have been poorly explored in humans.
Aim
The primary aim of this study is to determine the energy intake-independent effects of leptin on energy metabolism in lipodystrophic subjects. The major aspects of energy metabolism to be studied are:
- Lipid metabolism, including fasting lipids, lipolysis and fatty acid turnover, and ectopic lipid storage.
- Glucose metabolism, including fasting glucose, endogenous glucose production, and insulin sensitivity
- Energy expenditure, including total and resting energy expenditure, skeletal muscle work efficiency, and spontaneous physical activity
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 14 Years 至 70 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
结局指标
主要结局
Total Body Insulin Sensitivity
时间窗: Intervention 1 (5 days), Intervention 2 (14 days), and Long-term follow-up (6 months)
Total body insulin sensitivity (measured as glucose disposal rate during a hyperinsulinemic, euglycemic clamp)
次要结局
- Endogenous Rate of Appearance of Palmitate(Intervention 1 (5 days), Intervention 2 (14 days), and Long-term follow-up (6 months))
- Insulin-mediated Suppression of Hepatic Glucose Production(Intervention 1 (5 days), Intervention 2 (14 days), and Long-term follow-up (6 months))