Orlistat for the Treatment of Type I Hyperlipoproteinemia
Condition: Hyperlipoproteinemia Type I; Hypertriglyceridemia
MeSH terms: Hyperlipoproteinemia Type I; Hypertriglyceridemia; Hyperlipoproteinemias; Hyperlipidemias
Study type: Interventional
Phase: Phase 2

Summary: 
      Patients with Type I Hyperlipoproteinemia (T1HLP) have a rare form of hypertriglyceridemia
      marked by significant chylomicronemia and recurrent episodes of acute pancreatitis. T1HLP is
      caused by a deficiency of lipoprotein lipase or one of its cofactors. Many patients are a
      challenge to treat, as the only effective therapy available is an extremely low fat diet.
      This diet is exceedingly difficult to follow, and despite adherence, many patients still have
      chylomicronemia and develop acute pancreatitis.

      Specific Aim: To determine the efficacy of a gastric and pancreatic lipase inhibitor,
      Orlistat, in reducing serum triglyceride levels in patients with T1HLP.
    

Detailed description: 
      Type I hyperlipoproteinemia is a rare, autosomal recessive metabolic disorder characterized
      by extreme hypertriglyceridemia due to a deficiency in lipoprotein lipase or related
      proteins. Treatment of these patients is challenging as triglyceride-lowering medications are
      ineffective. A low fat diet is helpful, however, despite good dietary compliance, some
      patients continue to have severe hypertriglyceridemia and recurrent pancreatitis which can be
      life threatening. Therefore, Investigator wish to investigate whether inducing dietary fat
      malabsorption or inhibiting chylomicron formation will cause further lowering of serum
      triglycerides (TG) beyond the effect of limiting dietary fat intake.

      Investigator will study the efficacy and safety of an inhibitor of intestinal lipase
      (Orlistat) for reducing serum triglyceride levels in patients with Type I
      hyperlipoproteinemia. Investigator plan to enroll 20 patients with Type I
      hyperlipoproteinemia in a randomized, double-blind, placebo-controlled, cross-over trial.
      During the last week of each study period, fasting blood samples will be drawn for three
      consecutive days for serum lipids and chemistry panel. The primary endpoint will be serum
      triglycerides; the secondary endpoint variables will be fasting and postprandial serum
      chylomicron-TG levels, postprandial serum TG levels during a meal tolerance test and retinyl
      palmitate levels during a meal tolerance test. Repeated measures analysis of variance will be
      used for statistical comparisons.

      These results may help in designing novel therapeutic approaches for patients with Type 1
      hyperlipoproteinemia.
    

Intervention name(s): Orlistat
Intervention type(s): Drug
Intervention description(s): Orlistat is a gastric and pancreatic lipase inhibitor that is approved by the FDA for weight loss. It is available over-the-counter as 60 mg tablets under the trade name Alli, and available by prescription as 120 mg capsules under the trade name Xenical.
Other intervention name(s): Alli
Intervention MeSH terms: Orlistat
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)
Primary purpose: Treatment