The purpose of this study was to determine whether orlistat is effective in decreasing plasma unconjugated bilirubin levels in patients with Crigler-Najjar disease...
Date First Received: April 16, 2007
Last Updated: April 16, 2007
Verified by: University Medical Centre Groningen, April 2007
Clinical Trial Phase: N/A | Start Date: September 2003
Overall Status: Completed
Estimated Enrollment: 16
Brief Summary
Official Title: “Orlistat Treatment of Unconjugated Hyperbilirubinemia in Crigler-Najjar Disease; A Randomized Controlled Trial”
Condition Keyword(s):
Intervention(s):
The purpose of this study was to determine whether orlistat is effective in decreasing plasma unconjugated bilirubin levels in patients with Crigler-Najjar disease.
Study Type: Interventional
Study Design: Treatment, Randomized, Double-Blind, Placebo Control, Crossover Assignment, Efficacy Study
Detailed Clinical Trial 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.
Intervention(s) in this Clinical Trial
- Drug: orlistat
Outcome Measures for this Clinical Trial
Primary Measures
- decrease in plasma unconjugated bilirubin level during orlistat
- increase in fecal fat excretion during orlistat
- increase in fecal bilirubin concentration during orlistat
Criteria for Participation in this Clinical Trial
Inclusion Criteria:
- patients with Crigler-Najjar disease above the age of 7 years
Exclusion Criteria:
- cholestasis, chronic malabsorption syndrome, pregnancy
Gender Eligibility for this Clinical Trial: Both
Minimum Age for this Clinical Trial: 8 Years
Maximum Age for this Clinical Trial: N/A
Are Healthy Volunteers Accepted for this Clinical Trial?: No
Clinical Trial Sponsor Information
Lead Sponsor: University Medical Centre Groningen
Overall Clinical Trial Officials and Contacts
Anja M. Hafkamp, MD Principal Investigator University Medical Center Groningen and Erasmus University Medical Center
Related Publications
References
Hafkamp AM, Havinga R, Sinaasappel M, Verkade HJ. Effective oral treatment of unconjugated hyperbilirubinemia in Gunn rats. Hepatology. 2005 Mar;41(3):526-34.
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.
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.
Verkade HJ. A novel hypothesis on the pathophysiology of neonatal jaundice. J Pediatr. 2002 Oct;141(4):594-5. No abstract available.
Additional Information
Information obtained from ClinicalTrials.gov on November 20, 2008
Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00461799
Study ID Number: CN-01
ClinicalTrials.gov Identifier: NCT00461799
Health Authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
Clinical Trials Authorship and Review
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