Orlistat Treatment of Crigler-Najjar Disease

Crigler-Najjar Syndrome Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00461799
• Other study ID #: CN-01
• Status: Completed
• Phase: N/A
• First received: April 16, 2007
• Last updated: April 16, 2007
• Start date: September 2003
• Est. completion date: January 2004

Study information

• Verified date: April 2007
• Source: University Medical Center Groningen
• Contact: n/a
• Is FDA regulated: No
• Health authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 16
• Est. completion date: January 2004
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 8 Years and older

Eligibility

Inclusion Criteria:

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

Exclusion Criteria:

• cholestasis, chronic malabsorption syndrome, pregnancy

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Crossover Assignment, Masking: Double-Blind, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Crigler-Najjar Syndrome
• Hyperbilirubinemia

Intervention

Drug:
• orlistat

Locations

Country	Name	City	State
Netherlands	Erasmus University Medical Center	Rotterdam

Sponsors (3)

Lead Sponsor	Collaborator
University Medical Center Groningen	De Najjar Stichting, Erasmus Medical Center

Country where clinical trial is conducted

Netherlands, 

References & Publications (4)

Hafkamp AM, Havinga R, Ostrow JD, Tiribelli C, Pascolo L, Sinaasappel M, Verkade HJ. Novel kinetic insights into treatment of unconjugated hyperbilirubinemia: phototherapy and orlistat treatment in Gunn rats. Pediatr Res. 2006 Apr;59(4 Pt 1):506-12. Erratum in: Pediatr Res. 2007 Oct;62(4):488. — View Citation

Hafkamp AM, Havinga R, Sinaasappel M, Verkade HJ. Effective oral treatment of unconjugated hyperbilirubinemia in Gunn rats. Hepatology. 2005 Mar;41(3):526-34. — View Citation

Nishioka T, Hafkamp AM, Havinga R, vn Lierop PP, Velvis H, Verkade HJ. Orlistat treatment increases fecal bilirubin excretion and decreases plasma bilirubin concentrations in hyperbilirubinemic Gunn rats. J Pediatr. 2003 Sep;143(3):327-34. — View Citation

Verkade HJ. A novel hypothesis on the pathophysiology of neonatal jaundice. J Pediatr. 2002 Oct;141(4):594-5. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	decrease in plasma unconjugated bilirubin level during orlistat
Primary	increase in fecal fat excretion during orlistat
Primary	increase in fecal bilirubin concentration during orlistat