Compassionate Use of Metreleptin in Previously-Treated Patients With Generalized Lipodystrophy
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 入组人数
- 24
- 试验地点
- 1
- 主要终点
- Serum triglycerides
研究概览
简要总结
Background:
- Generalized lipodystrophy can cause high blood fat levels and resistance to insulin. This can lead to health problems including diabetes. Researchers have found that the drug metreleptin improves health in people with this disease.
Objective:
- To test the safety and effectiveness of metreleptin.
Eligibility:
- People ages 6 months and older with generalized lipodystrophy who:
- have received metreleptin through NIH studies AND
- cannot get it through approved or compassionate use mechanisms in their home country.
Design:
- Participants will come to NIH approximately every 6 months during year one, then every 1 2 years. Financial assistance may be available for travel within the U.S.
- At visits, participants will get a supply of metreleptin to take home for daily injections. They will have:
- plastic catheter placed in an arm vein.
- blood tests, urine collection, and physical exam.
- oral glucose tolerance test, drinking a sweet liquid.
- ultrasound of the heart, liver, uterus, and ovaries. A gel and a probe are placed on the skin and pictures are taken of the organs.
- echocardiogram, which takes pictures of the heart with sound waves.
- Resting Metabolic Rate taken. A plastic hood is worn over the head while the oxygen they breathe is measured.
- Participants will have up to 3 DEXA scan x-rays per year.
- Participants may have:
- annual bone x-rays.
- liver biopsies every few years. A needle will be inserted into the liver to obtain a small piece. Participants will sign a separate consent for this.
- Participants must be seen regularly by their local doctors and have blood tests at least every 3 6 months at home.
详细描述
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 the very rare condition of generalized lipodystrophy have leptin deficiency secondary to lack of adipose tissue. The combination of leptin deficiency and ectopic lipid deposition in patients with lipodystrophy leads to metabolic complications including severe insulin resistance and diabetes, hypertriglyceridemia, nonalcoholic steatohepatitis, and polycystic ovarian syndrome. Between 2000 and 2014, the NIDDK IRP conducted an open-label clinical trial of the recombinant human leptin analog, metreleptin, in patients with generalized and partial forms of lipodystrophy. This study showed that metreleptin ameliorates metabolic and endocrine abnormalities in lipodystrophy, including reducing food intake, improving insulin resistance and diabetes, reducing ectopic lipid, and normalizing reproduction. Based on these data, metreleptin was approved by the FDA in February, 2014, for patients with generalized, but not partial, lipodystrophy.
Currently, metreleptin is not available as an approved drug outside the US and Japan, and it is available on a compassionate use basis only in a few additional countries. The purpose of this study is twofold:
- To provide access to metreleptin to patients with generalized lipodystrophy, including those who have previously received metreleptin through NIH studies (protocols 02-DK-0022 and 13-DK- 0057) AND/OR who cannot obtain metreleptin through approved or compassionate use mechanisms in their home country
- To continue to collect data on the long-term efficacy of metreleptin in ameliorating the metabolic complications of generalized lipodystrophy.
Metreleptin will be given at doses of less than or equal to 0.24 mg/kg/day, adjusted based on body weight and metabolic control. Patients will be seen approximately once per year at NIH for evaluation, and potentially less frequently for those who are medically stable and have difficulty traveling to the US. Laboratory evaluation will be obtained more frequently by the patient s home providers as clinically indicated. The primary outcomes of the study are improvements in serum triglycerides and hemoglobin A1c levels. Secondary outcomes include measures of steatohepatitis and ectopic lipid, body composition, bone mineral density and bone mineral metabolism, and pituitary and reproductive function.
Metreleptin is supplied by Chiesi USA, Inc.. Neither the NIH nor Chiesi USA, Inc. can guarantee that leptin will be available for these patients indefinitely and/or after the study ends.
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
- 6 Months 至 98 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •INCLUSION CRITERIA:
- •Age greater than or equal to 6 months.
- •Generalized lipodystrophy (either congenital or acquired).
- •Those who cannot obtain metreleptin through approved or compassionate use mechanisms in their home country.
排除标准
- •Availability of metreleptin to the patient either as an approved drug, or through local compassionate use or expanded access programs.
- •Known HIV infection or HIV-associated lipodystrophy.
- •Any medical condition or medication that will increase risk to the subject.
- •Current alcohol or substance abuse.
- •Subjects who have a known hypersensitivity to E. coli derived proteins (as leptin is derived from such proteins).
研究组 & 干预措施
Leptin study drug
Administration of study drug SQ BID
干预措施: Metreleptin (Drug)
结局指标
主要结局
Serum triglycerides
时间窗: every 6-12 months
Improvements in lab value.
Serum hemoglobin A1C
时间窗: every 6-12 months
Improvements in lab value.
次要结局
- Ectopic lipid & body composition(every 12 months)
- Steatohepatosis(every 12 months)
- Bone mineral density & metabolism(every 12 months)
- Pituitary & Reproductive Function(every 6-12 months)