A Randomized, Double Blind, Placebo-Controlled Study to Assess Efficacy, Safety and Tolerability of ISIS 304801 in Patients With Partial Lipodystrophy With an Open-Label Extension
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 5
- 试验地点
- 1
- 主要终点
- Change in Log 10 Fasting Triglycerides.
研究概览
简要总结
Background:
Partial lipodystrophy is a deficiency of body fat in parts of the body (usually the arms and legs). People with partial lipodystrophy often get high blood triglyceride (fat) level, insulin resistance, diabetes and other problems. Researchers think the new drug ISIS 304801 can help treat health problems caused by partial lipodystrophy.
Objective:
To see if ISIS 304801 will improve blood fat (triglyceride levels), diabetes, and liver disease, and reduce some risks for heart disease caused by partial lipodystrophy.
Eligibility:
Adults at least 18 years old with partial lipodystrophy.
Design:
Participants will be screened during a 1-week stay at NIH. They will have:
Blood and urine tests
Physical exam.
Assignment to get either the study drug or placebo.
Instructions for how to inject the drug.
Body measurements.
Heart tests.
Participants will give themselves injections of the drug or placebo once a week at home. Some may test blood sugar by finger pricks. They will have monthly phone calls and nurse visits to take blood tests.
After 4 months, participants may continue the study for 1 year. All participants will get the study drug.
Participants will have study visits at NIH every 4 months. These may include:
Insulin sensitivity measurement: Insulin and sugar will be infused through 2 intravenous (IV) lines in the arms. Blood will be drawn.
Sugar and fat metabolism measured by IV infusions and blood tests.
Special x-ray scan to measure body fat.
Liquid meal then blood collected by IV catheter in the arm.
Magnetic resonance imaging scans.
Neck ultrasound.
Questionnaires.
Liver biopsy (optional)
Injection of heparin (a blood thinner) before a blood test.
After finishing the drug, participants will have 1 nurse visit and 1 visit to NIH.
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详细描述
Background:
Lipodystrophy is a rare disease of deficient adipose mass, characterized by severe hypertriglyceridemia as well as insulin resistance, diabetes mellitus, fatty liver disease, acute pancreatitis, and early cardiovascular events. Apolipoprotein C-III (apoC-III) regulates triglyceride metabolism, and apoC-III levels strongly correlate with serum triglycerides in a variety of patient populations. Patients with genetically low levels of apoC-III have lower triglycerides and reduced cardiovascular disease, while individuals with genetically elevated levels of apoC-III have higher triglycerides and increased non-alcoholic fatty liver disease and insulin resistance. Pharmacologic reduction of apoC-III using anti-sense oligonucleotides (ASOs) reduce triglycerides by ~60-70% in a tested patient populations.
Aim:
The purpose of this study is to determine if apoC-III reduction using an ASO to apoC-III (ISIS 304801) will reduce triglycerides and improve insulin resistance, diabetes, and hepatic steatosis in patients with lipodystrophy.
The primary hypothesis to be tested is:
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（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
研究组 & 干预措施
Placebo
Placebo administered subcutaneously (SC)
干预措施: Placebo (Drug)
ISIS 304801
300 mg of study drug administered via SC
干预措施: ISIS 304801 (Drug)
结局指标
主要结局
Change in Log 10 Fasting Triglycerides.
时间窗: Baseline and 16 weeks
Change from baseline to 16 weeks in log 10 fasting triglycerides
次要结局
- Change in HbA1c(Baseline and 16 weeks)
- Plasma ISIS 304801 Level(16 weeks)
- Change in Lipolysis Rate (Palmitate)(Baseline and 16 weeks)
- Change From Baseline in Liver Volume(Baseline and 16 weeks)
- Change in Lipolysis Rate (Glycerol)(Baseline and 16 weeks)
- Change From Baseline in Hepatic Steatosis(Baseline and 16 weeks)
- Change in Fasting Plasma Glucose(Baseline and 16 weeks)
- Change in Lipoprotein Lipase Activity(Baseline and 16 weeks)
- Change in Total Body Insulin Sensitivity(Baseline and 16 weeks)