Orlistat Therapy for Children With Type 1 Hyperlipoproteinemia: A Randomized Clinical Trial

Abstract

Context: Patients with type 1 hyperlipoproteinemia (T1HLP), a rare genetic disorder, have extreme chylomicronemia and recurrent episodes of acute pancreatitis. Currently, the only therapeutic option is to consume an extremely low-fat diet because the triglyceride-lowering medications are not efficacious.

Objective: To determine the efficacy of orlistat, a gastric and pancreatic lipase inhibitor, in reducing serum triglyceride levels in patients with T1HLP.

Design and setting: We conducted a randomized, open-label, clinical trial with a four-period, two-sequence ("orlistat" and "off orlistat" for 3 months), crossover study design.

Patients: Two unrelated young Asian Indian males (11 and 9 years old) with T1HLP due to homozygous large GPIHBP1 deletions were enrolled at the UT Southwestern Medical Center. The patients were randomized to receive 3 months of orlistat or no therapy (off), then crossed over to the other arm, and this sequence was then repeated. Fasting serum triglyceride levels, fat-soluble vitamins, and gastrointestinal side effects were assessed.

Results: Compared with the two off periods, orlistat therapy reduced serum triglycerides by 53.3% and 53.0% in patient 1 and 45.8% and 62.2% in patient 2. There was no deficiency of fat-soluble vitamin levels, and their growth continued. There were no serious adverse effects of orlistat; patient 1 had a mild increase in passage of gas and bloating, and patient 2 had constipation with mild stool leakage.

Conclusion: Orlistat is safe and highly efficacious in lowering serum triglycerides in children with T1HLP and should be the first-line therapy in conjunction with an extremely low-fat diet.

Trial registration: ClinicalTrials.gov NCT02767531.

Figures

Figure 1.

Height and weight growth in patients during the study. The shaded areas indicate the treatment periods, the solid symbols represent the visit after being on orlistat, and the unfilled symbols represent the baseline and the visit after being off orlistat for 3 months, respectively. Both patients continued to grow well in height and weight during the study.