Orlistat Treatment of Crigler-Najjar Disease

This study has been completed.
Sponsor:
Collaborators:
Erasmus Medical Center
De Najjar Stichting
Information provided by:
University Medical Centre Groningen
ClinicalTrials.gov Identifier:
NCT00461799
First received: April 16, 2007
Last updated: NA
Last verified: April 2007
History: No changes posted
  Purpose

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
Crigler-Najjar Syndrome
Drug: orlistat

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double-Blind
Primary Purpose: Treatment
Official Title: Orlistat Treatment of Unconjugated Hyperbilirubinemia in Crigler-Najjar Disease; A Randomized Controlled Trial

Resource links provided by NLM:


Further study details as provided by University Medical Centre Groningen:

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

Estimated Enrollment: 16
Study Start Date: September 2003
Study Completion Date: January 2004
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.

  Eligibility

Ages Eligible for Study:   8 Years and older
Genders Eligible for Study:   Both
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
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00461799

Locations
Netherlands
Erasmus University Medical Center
Rotterdam, Netherlands, 3015 GJ
Sponsors and Collaborators
University Medical Centre 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 Centre Groningen
  More Information

Publications:
ClinicalTrials.gov Identifier: NCT00461799     History of Changes
Other Study ID Numbers: CN-01
Study First Received: April 16, 2007
Last Updated: April 16, 2007
Health Authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)

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

Additional relevant MeSH terms:
Crigler-Najjar Syndrome
Hyperbilirubinemia
Cardiomyopathies
Hyperbilirubinemia, Hereditary
Metabolism, Inborn Errors
Genetic Diseases, Inborn
Metabolic Diseases
Pathologic Processes
Heart Diseases
Cardiovascular Diseases
Orlistat
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Anti-Obesity Agents
Central Nervous System Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on August 26, 2014