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Orlistat Treatment of Crigler-Najjar Disease

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ClinicalTrials.gov Identifier: NCT00461799
Recruitment Status : Completed
First Posted : April 18, 2007
Last Update Posted : April 18, 2007
Sponsor:
Collaborators:
Erasmus Medical Center
De Najjar Stichting
Information provided by:
University Medical Center Groningen

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 Not Applicable

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 Type : Interventional  (Clinical Trial)
Enrollment : 16 participants
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 : September 2003
Actual Study Completion Date : January 2004





Primary Outcome Measures :
  1. decrease in plasma unconjugated bilirubin level during orlistat
  2. increase in fecal fat excretion during orlistat
  3. increase in fecal bilirubin concentration during orlistat


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Ages Eligible for Study:   8 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

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

Exclusion Criteria:

  • cholestasis, chronic malabsorption syndrome, pregnancy

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00461799


Locations
Netherlands
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

Publications:
ClinicalTrials.gov Identifier: NCT00461799     History of Changes
Other Study ID Numbers: CN-01
First Posted: April 18, 2007    Key Record Dates
Last Update Posted: April 18, 2007
Last Verified: April 2007

Keywords provided by University Medical Center Groningen:
Crigler-Najjar disease.
Bilirubin.
Phototherapy.
Orlistat.
Unconjugated hyperbilirubinemia.

Additional relevant MeSH terms:
Hyperbilirubinemia
Crigler-Najjar Syndrome
Pathologic Processes
Hyperbilirubinemia, Hereditary
Metabolism, Inborn Errors
Genetic Diseases, Inborn
Metabolic Diseases
Orlistat
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-Obesity Agents