Long Term Efficacy and Safety of Orlistat for Type 1 Hyperlipoproteinemia: a Randomized, Double-blind, Placebo-controlled Trial
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 28
- 试验地点
- 2
- 主要终点
- Change in Triglycerides
研究概览
简要总结
Type I hyperlipoproteinemia (T1HLP, also known as familial chylomicronemia syndrome or FCS) is a rare diseasewhere the blood triglycerides (fats) are very high. It is caused by lack of certain enzymes and proteins in the bodythat are important in disposing circulating fats from blood. Treatment of T1HLP patients who have very high levels of blood fats (≥ 1,000 mg/dL) is challenging as conventional triglyceride-lowering medications, such as fibrates and fishoil, are ineffective.
The purpose of this trial is to study the long-term efficacy and safety of orlistat for reducing blood triglyceride levels in patients with T1HLP.
详细描述
The hypotheses to be tested and the specific aims are:
Hypothesis 1: As compared to placebo, Orlistat will be effective and safe in lowering fasting serum TG concentrations in patients with T1HLP.
Specific Aim 1: To investigate the efficacy and safety of Orlistat for reducing fasting serum TG levels in 28 patients with T1HLP in a double-blind, randomized, placebo-controlled, parallel design study for a period of 24 weeks.
Hypothesis 2: The efficacy and safety of Orlistat in patients with T1HLP will be maintained over a period of up to 48 weeks.
Specific Aim 2: To investigate the efficacy and safety of Orlistat in patients with T1HLP in an open-label extension study for a period of up to 48 weeks-.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Diagnostic
- 盲法
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 8 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age ≥ 8 years
- •Type I hyperlipoproteinemia confirmed by bi-allelic disease-causing variants in any one of the T1HLP genes (LPL, APOC2, APOA5, LMF1, GPIHBP1, or GCKR).
- •Subjects with digenic inheritance with heterozygous disease-causing variants in two different T1HLP genes.
- •Subjects who have a fasting TG greater than or equal to 750 mg/dL at the end of run-in period of 8 weeks will be eligible for randomization.
- •Subjects who do not have confirmed genetic mutation for Type 1 hyperlipoproteinemia but have a fasting TG greater than or equal to 750 mg/dL at the end of run-in period of 8 weeks will be eligible for randomization.
- •Well controlled diabetes mellitus with hemoglobin A1c < 8%
- •Off orlistat for a period of 2 months
- •Patients on Olezarsen and Plozasiran (APOC3 antisense oligonucleotide) can enroll if on the drug for more than 3 months
- •Following methods of contraception for males and females of childbearing age will be employed Males: Being in this research may damage your sperm, which could cause harm to a child that you may father while on this study. If you take part in this study and are sexually active, you must agree to use a medically-acceptable form of birth control. Medically-acceptable forms of birth control include: (1) surgical sterilization (vasectomy), or (2) a condom used with a spermicide (a substance that kills sperm).
- •Females: If you are part of this study while pregnant or breast-feeding an infant, it is possible that you may expose the unborn child or infant to risks. For that reason, pregnant and breast-feeding females cannot participate in the study. If you can become pregnant, a blood or urine pregnancy test will be done, and it must be negative before you participate in this study. If you take part in this study and you are sexually active, you and any person that you have sex with must use medically-acceptable birth control (contraceptives) during the study. Medically-acceptable birth control (contraceptives) includes: (1) surgical sterilization (such as hysterectomy or "tubes tied"), (2) approved hormonal contraceptives (such as birth control pills, patch or ring; Depo-Provera, Implanon), (3) barrier methods (such as condom or diaphragm) used with a spermicide (a substance that kills sperm), or (4) an intrauterine device (IUD). If you do become pregnant during this study, you must tell the researchers immediately.
排除标准
- •Secondary hypertriglyceridemia due to diabetes, renal disease, alcoholism and drug therapy such as estrogens and estrogen analogues, steroids, HIV-1 protease inhibitors, retinoic acid derivatives, interferons, or lasparaginase.
- •On lomitapide or participating in clinical trial of volanesorsen.
- •On cyclosporine
- •Having serum TSH outside of the normal range if on levothyroxine supplementation.
- •Use of levothyroxine to suppress TSH in individuals with thyroid cancer.
- •Pregnant or lactating women
- •Significant liver disease (elevated transaminases > 2 times upper limit of normal)
- •Alcohol abuse (> 7 drinks or 84 g per week for women and > 14 drinks or 168 g per week for men)
- •Severe anemia (hematocrit < 24%)
- •Illicit drug use (cocaine, marijuana, LSD, etc.)
- •Major surgery in the past three months
- •Congestive heart failure
- •Serum creatinine greater than 2.5 mg/dL
- •Cancer within the past five years
- •Gastrointestinal surgery in the past
- •Current therapy with anti-coagulants, digoxin and anti-arrhythmics
- •Chronic malabsorption syndromes
- •Cholestasis
- •Acute illnesses such as acute pancreatitis in the last 8 weeks
- •Previous history of renal calcium oxalate stones
研究组 & 干预措施
Placebo
Placebo will be given orally.
干预措施: Placebo (Drug)
Orlistat Drug
Drug will be given orally.
干预措施: Orlistat (Drug)
结局指标
主要结局
Change in Triglycerides
时间窗: 24 weeks
Change in fasting serum TG levels weeks compared to the baseline fasting serum TG levels .
次要结局
未报告次要终点
研究者
Abhimanyu Garg
Professor
University of Texas Southwestern Medical Center