Orlistat Treatment of Crigler-Najjar Disease
April 16, 2007 updated by: University Medical Center Groningen
Orlistat Treatment of Unconjugated Hyperbilirubinemia in Crigler-Najjar Disease; A Randomized Controlled Trial
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 Overview
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
Enrollment
16
Phase
- Not Applicable
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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Rotterdam, Netherlands, 3015 GJ
- Erasmus University Medical Center
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
8 years and older (Child, Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
Inclusion Criteria:
- patients with Crigler-Najjar disease above the age of 7 years
Exclusion Criteria:
- cholestasis, chronic malabsorption syndrome, pregnancy
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Crossover Assignment
- Masking: Double
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
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decrease in plasma unconjugated bilirubin level during orlistat
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increase in fecal fat excretion during orlistat
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increase in fecal bilirubin concentration during orlistat
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
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 and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
General Publications
- Hafkamp AM, Havinga R, Sinaasappel M, Verkade HJ. Effective oral treatment of unconjugated hyperbilirubinemia in Gunn rats. Hepatology. 2005 Mar;41(3):526-34. doi: 10.1002/hep.20589.
- 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. doi: 10.1203/01.pdr.0000203180.79636.98. Erratum In: Pediatr Res. 2007 Oct;62(4):488.
- 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. doi: 10.1067/s0022-3476(03)00298-1.
- Verkade HJ. A novel hypothesis on the pathophysiology of neonatal jaundice. J Pediatr. 2002 Oct;141(4):594-5. No abstract available.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start
September 1, 2003
Study Completion (Actual)
January 1, 2004
Study Registration Dates
First Submitted
April 16, 2007
First Submitted That Met QC Criteria
April 16, 2007
First Posted (Estimate)
April 18, 2007
Study Record Updates
Last Update Posted (Estimate)
April 18, 2007
Last Update Submitted That Met QC Criteria
April 16, 2007
Last Verified
April 1, 2007
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- CN-01
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