Orlistat Treatment of Crigler-Najjar Disease

Not Applicable

Completed

• Conditions: Crigler-Najjar Syndrome

• Registration Number: NCT00461799
• Lead Sponsor: University Medical Center Groningen

Brief Summary

The purpose of this study was to determine whether orlistat is effective in decreasing plasma unconjugated bilirubin levels in patients with Crigler-Najjar disease.

Detailed Description

Unconjugated hyperbilirubinemia in Crigler-Najjar (CN) disease is conventionally treated with phototherapy and/or phenobarbital. Life-long daily phototherapy has considerable disadvantages. Main problems are a decreasing efficacy with age and a profound impact of the intensive phototherapy regimen on the quality of (social) life. An alternative treatment option for unconjugated hyperbilirubinemia is based on intestinal capture of UCB by oral treatment. Particularly when plasma UCB concentrations are high as in CN disease, UCB can diffuse from the blood into the intestinal lumen across the mucosa. Intestinal capture of UCB followed by fecal excretion reduces the enterohepatic circulation of UCB and subsequently decreases plasma UCB concentration. We demonstrated in Gunn rats, the animal model for CN disease, that orlistat treatment decreases plasma UCB concentrations parallel with increased fecal fat excretion, and induces net transmucosal excretion of UCB from the blood into the intestinal lumen. In human adults, orlistat has been widely applied for treatment of obesity, without serious side effects. Recent studies in obese adolescents and prepubertal children indicate that short-term orlistat treatment is well-tolerated by children and generally has only mild side effects. In the present randomized, placebo-controlled trial we determined in patients with CN disease the effects of orlistat treatment on plasma UCB concentrations, and on fecal excretion of fat and UCB.

Study Timeline

• Study Start: 2003-09
• Study Completion: 2004-01
• Status Verified: 2007-04
• Study First Submitted: 2007-04-16
• Study First Submitted QC: 2007-04-16
• Last Update Submitted: 2007-04-16
• Study First Posted: 2007-04-18
• Last Update Posted: 2007-04-18

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 16

Inclusion Criteria

• patients with Crigler-Najjar disease above the age of 7 years

Exclusion Criteria

• cholestasis, chronic malabsorption syndrome, pregnancy

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Primary Outcome Measures

Name	Time	Method
decrease in plasma unconjugated bilirubin level during orlistat
increase in fecal fat excretion during orlistat
increase in fecal bilirubin concentration during orlistat

Trial Locations

Locations (1)

Erasmus University Medical Center; 🇳🇱 Rotterdam, Netherlands