RECRUITINGPhase 2INTERVENTIONAL

Long Term Efficacy and Safety of Orlistat for Type 1 Hyperlipoproteinemia

Long Term Efficacy and Safety of Orlistat for Type 1 Hyperlipoproteinemia: a Randomized, Double-blind, Placebo-controlled Trial

About This Trial

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.

Who May Be Eligible (Plain English)

* 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 Who Should NOT Join This Trial: - 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 and olezarsen - 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 Always talk to your doctor about whether this trial is right for you.

Original Eligibility Criteria

View original clinical language

* 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 inhibitors, retinoic acid derivatives, interferons, or lasparaginase. * On lomitapide or participating in clinical trial of volanesorsen and olezarsen * 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

Treatments Being Tested

DRUG

Orlistat

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).

DRUG

Placebo

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).

Locations (1)

UT southwestern Medical Center

Dallas, Texas, United States