Clinical Trial: Orlistat Treatment of Crigler-Najjar Disease

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: Orlistat Treatment of Unconjugated Hyperbilirubinemia in Crigler-Najjar Disease; A Randomized Controlled Trial

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 Summary: 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.
Sponsor: University Medical Center Groningen

Current Primary Outcome:

  • decrease in plasma unconjugated bilirubin level during orlistat
  • increase in fecal fat excretion during orlistat
  • increase in fecal bilirubin concentration during orlistat


Original Primary Outcome: Same as current

Current Secondary Outcome:

Original Secondary Outcome:

Information By: University Medical Center Groningen

Dates:
Date Received: April 16, 2007
Date Started: September 2003
Date Completion:
Last Updated: April 16, 2007
Last Verified: April 2007