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Sponsors and Collaborators: |
University Medical Centre Groningen Erasmus Medical Center De Najjar Stichting |
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Information provided by: | University Medical Centre Groningen |
ClinicalTrials.gov Identifier: | NCT00461799 |
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 | Intervention |
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Crigler-Najjar Syndrome |
Drug: orlistat |
Study Type: | Interventional |
Study Design: | Treatment, Randomized, Double-Blind, Placebo Control, Crossover Assignment, Efficacy Study |
Official Title: | Orlistat Treatment of Unconjugated Hyperbilirubinemia in Crigler-Najjar Disease; A Randomized Controlled Trial |
Estimated Enrollment: | 16 |
Study Start Date: | September 2003 |
Study Completion Date: | January 2004 |
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.
Ages Eligible for Study: | 8 Years and older |
Genders Eligible for Study: | Both |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
Exclusion Criteria:
Netherlands | |
Erasmus University Medical Center | |
Rotterdam, Netherlands, 3015 GJ |
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 Centre Groningen |
Study ID Numbers: | CN-01 |
Study First Received: | April 16, 2007 |
Last Updated: | April 16, 2007 |
ClinicalTrials.gov Identifier: | NCT00461799 History of Changes |
Health Authority: | Netherlands: The Central Committee on Research Involving Human Subjects (CCMO) |
Crigler-Najjar disease. Bilirubin. Phototherapy. Orlistat. Unconjugated hyperbilirubinemia. |
Anti-Obesity Agents Metabolism, Inborn Errors Orlistat Metabolic Diseases Genetic Diseases, Inborn Hyperbilirubinemia |
Crigler Najjar Syndrome, Type 1 Bilirubin Cardiogenital Syndrome Metabolic Disorder Crigler-Najjar Syndrome |
Hyperbilirubinemia, Hereditary Metabolic Diseases Disease Molecular Mechanisms of Pharmacological Action Enzyme Inhibitors Crigler-Najjar Syndrome Pharmacologic Actions Anti-Obesity Agents |
Metabolism, Inborn Errors Orlistat Pathologic Processes Genetic Diseases, Inborn Therapeutic Uses Hyperbilirubinemia Syndrome Central Nervous System Agents |