Long Term Efficacy and Safety of Orlistat for Type 1 Hyperlipoproteinemia: a Randomized, Double-blind, Placebo-controlled Trial
University of Texas Southwestern Medical Center
Summary
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.
Description
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 a…
Eligibility
- Age range
- 8+ years
- Sex
- All
- Healthy volunteers
- No
* 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 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. * Age ≥ 8 years * Well controlled diabetes mellitus with hemoglobin A1c \< 8% * Off orlistat for a period of 2 months Exclusion Criteria: * Secondary hypertriglyceridemia due to diabetes, renal disease, , alcoholism and drug therapy such as estrogens and estrogen analogues, steroids, HIV-1 protease i…
Interventions
- DrugOrlistat
Orlistat is an inhibitor of gastric and pancreatic lipases and can reduce dietary fat absorption by 30%. Orlistat at a dose of 2 capsules (each containing 60 mg of active drug) three times a day with each meal (a total dose of 360 mg daily).
- DrugPlacebo
Placebo at a dose of 2 capsules (each containing 60 mg placebo) three times a day with each meal (a total dose of 360 mg daily).
Location
- UT southwestern Medical CenterDallas, Texas