Orlistat Treatment of Crigler-Najjar Disease

Sponsor

University Medical Center Groningen (Other)

Overall Status

Completed

CT.gov ID

NCT00461799

Collaborator

Erasmus Medical Center (Other), De Najjar Stichting (Other)

Enrollment

Location

Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Crigler-Najjar Syndrome	Drug: orlistat	N/A

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 Design

Study Type:

Interventional

Allocation:

Randomized

Intervention Model:

Crossover Assignment

Masking:

Double

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Sep 1, 2003

Actual Study Completion Date :

Jan 1, 2004

Outcome Measures

Primary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

8 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

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

Exclusion Criteria:

cholestasis, chronic malabsorption syndrome, pregnancy

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Erasmus University Medical Center	Rotterdam		Netherlands	3015 GJ

Sponsors and Collaborators

University Medical Center Groningen
Erasmus Medical Center
De Najjar Stichting

Investigators

Principal Investigator: Anja M. Hafkamp, MD, University Medical Center Groningen and Erasmus University Medical Center
Study Chair: Maarten Sinaasappel, MD, Erasmus Medical Center
Study Director: Henkjan J. Verkade, MD, PhD, University Medical Center Groningen