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Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT00461799
Other study ID # CN-01
Secondary ID
Status Completed
Phase N/A
First received April 16, 2007
Last updated April 16, 2007
Start date September 2003
Est. completion date January 2004

Study information

Verified date April 2007
Source University Medical Center Groningen
Contact n/a
Is FDA regulated No
Health authority Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
Study type Interventional

Clinical Trial 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.


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.


Recruitment information / eligibility

Status Completed
Enrollment 16
Est. completion date January 2004
Est. primary completion date
Accepts healthy volunteers No
Gender Both
Age group 8 Years and older
Eligibility Inclusion Criteria:

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

Exclusion Criteria:

- cholestasis, chronic malabsorption syndrome, pregnancy

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Crossover Assignment, Masking: Double-Blind, Primary Purpose: Treatment


Related Conditions & MeSH terms


Intervention

Drug:
orlistat


Locations

Country Name City State
Netherlands Erasmus University Medical Center Rotterdam

Sponsors (3)

Lead Sponsor Collaborator
University Medical Center Groningen De Najjar Stichting, Erasmus Medical Center

Country where clinical trial is conducted

Netherlands, 

References & Publications (4)

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. Erratum in: Pediatr Res. 2007 Oct;62(4):488. — View Citation

Hafkamp AM, Havinga R, Sinaasappel M, Verkade HJ. Effective oral treatment of unconjugated hyperbilirubinemia in Gunn rats. Hepatology. 2005 Mar;41(3):526-34. — View Citation

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. — View Citation

Verkade HJ. A novel hypothesis on the pathophysiology of neonatal jaundice. J Pediatr. 2002 Oct;141(4):594-5. — View Citation

Outcome

Type Measure Description Time frame Safety issue
Primary decrease in plasma unconjugated bilirubin level during orlistat
Primary increase in fecal fat excretion during orlistat
Primary increase in fecal bilirubin concentration during orlistat
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