Nonalcoholic Steatohepatitis: is Leptin an Etiological Factor (Phase 2).
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 9
- 试验地点
- 1
- 主要终点
- Non-alcoholic Steatohepatitis Score as Determined by Liver Histopathology at 12 Months
研究概览
简要总结
Nonalcoholic steatohepatitis (or NASH) is known to be caused by deposition of fat in the liver and development of scarring. This condition occurs more frequently in overweight and obese persons. It is often associated with resistance to the actions of insulin hormone. Fat cells secrete a hormone called leptin. Recently, we have learned that obese or overweight persons make too much leptin, which may contribute to insulin resistance. Paradoxically, patients who do not have any fat cells, also have insulin resistance. In these patients, insulin resistance is caused by the absence of leptin and leptin replacement significantly improves insulin resistance and fat deposition in the liver. In an earlier study, we determined the leptin levels in patients with NASH and how these levels are related to body fat levels as well as responsiveness to insulin. We saw that a subgroup of patients with NASH have relatively low levels of leptin in contrast to the amount of body fat they had. We now would like to see if restoring leptin levels to normal will improve the disease process in these patients. Our study patients will be male patients, aged between 18 and 65 (inclusive), who do not have any other cause for their liver disease. We have put some restrictions in body size such that a spectrum of patients from normal weight to obese range would be included. They will also demonstrate low leptin levels (levels similar to only 25% of normal population). We will use a genetically engineered form of leptin manufactured by Amylin Inc. given via injections under the skin. We plan to continue therapy for a period of one year and evaluate the change in liver disease by a liver biopsy. We will also follow the metabolic parameters and body composition characteristics that we examined in our earlier study. We expect that patients with low blood leptin levels will show improvement in their liver disease and insulin resistance when their blood leptin levels are restored to normal.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •Biopsy proven NASH
- •Circulating fasting leptin <9 ng/mL (staggered criteria for different BMI levels)
排除标准
- •Presence of advanced liver disease (as evidenced by abnormal synthetic function, abnormal prothrombin time or albumin)
- •Presence of clinical lipodystrophy
- •Presence of other liver disease
- •Presence of clinical diabetes (fasting >126 mg/dL or 2 hour post 75 g-glucose >200 mg/dL or random glucose >200 mg/dL with presence of diabetes symptoms or known history of diabetes)
- •Any medication for treatment of NASH or obesity
- •Presence of HIV
- •Inability to give informed consent
- •Presence of end-stage renal disease, any type of active cancer, or >class 2 congestive heart failure ((New York Heart Association Functional Classification System), based on medical history and physical examination
- •Presence of any other condition that limits life expectancy to <2 years
- •Active infection (may be transient)
- •Any other condition in the opinion of the investigators that may impede successful data collection
研究组 & 干预措施
Metreleptin treatment group
Treatment group
干预措施: metreleptin (Drug)
结局指标
主要结局
Non-alcoholic Steatohepatitis Score as Determined by Liver Histopathology at 12 Months
时间窗: 1 year
Non-alcoholic steatohepatitis (NASH) score after approximately one year of treatment with metreleptin. Total NASH scores can range from 0 to 14. The higher the NASH score the more severe the liver disease.
次要结局
- Liver Fat Percentage by Magnetic Resonance Imaging (MRI - Dixon Method) at 12 Months(1 year)
- Liver Function Test: Alanine Aminotransferase (ALT) Values at 12 Months(1 year)
- Liver Function Test: Aspartate Aminotransferase (AST) Values at 12 Months(1 year)
- Body Weight at 12 Months(1 year)
- Insulin Resistance: Homeostatic Model Assessment (HOMA) at 12 Months(1 year)
- Fasting Glucose Value at 12 Months(1 year)
- Fasting Triglycerides Value at 12 Months(1 year)
研究者
Elif Oral
Associate Prof of Medicine
University of Michigan