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Orlistat Treatment of Crigler-Najjar Disease

Primary Purpose

Crigler-Najjar Syndrome

Status

Completed

Phase

Not Applicable

Locations

Netherlands

Study Type

Interventional

Intervention

orlistat

About this trial

This is an interventional treatment trial for Crigler-Najjar Syndrome focused on measuring Crigler-Najjar disease., Bilirubin., Phototherapy., Orlistat., Unconjugated hyperbilirubinemia.

Eligibility Criteria

8 Years - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

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

Exclusion Criteria:

cholestasis, chronic malabsorption syndrome, pregnancy

Sites / Locations

Erasmus University Medical Center

Outcomes

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

Secondary Outcome Measures

Full Information

NCT ID

NCT00461799

First Posted

April 16, 2007

Last Updated

April 16, 2007

Sponsor

University Medical Center Groningen

Collaborators

Erasmus Medical Center, De Najjar Stichting

1. Study Identification

Unique Protocol Identification Number

NCT00461799

Brief Title

Orlistat Treatment of Crigler-Najjar Disease

Official Title

Orlistat Treatment of Unconjugated Hyperbilirubinemia in Crigler-Najjar Disease; A Randomized Controlled Trial

Study Type

Interventional

2. Study Status

Record Verification Date

April 2007

Overall Recruitment Status

Completed

Study Start Date

September 2003 (undefined)

Primary Completion Date

undefined (undefined)

Study Completion Date

January 2004 (Actual)

3. Sponsor/Collaborators

Name of the Sponsor

University Medical Center Groningen

Collaborators

Erasmus Medical Center, De Najjar Stichting

4. Oversight

Data Monitoring Committee

5. Study Description

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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Crigler-Najjar Syndrome

Keywords

Crigler-Najjar disease., Bilirubin., Phototherapy., Orlistat., Unconjugated hyperbilirubinemia.

7. Study Design

Primary Purpose

Treatment

Study Phase

Not Applicable

Interventional Study Model

Crossover Assignment

Masking

Double

Allocation

Randomized

Enrollment

16 (false)

8. Arms, Groups, and Interventions

Intervention Type

Drug

Intervention Name(s)

orlistat

Primary Outcome Measure Information:

Title

decrease in plasma unconjugated bilirubin level during orlistat

Title

increase in fecal fat excretion during orlistat

Title

increase in fecal bilirubin concentration during orlistat

10. Eligibility

Sex

All

Minimum Age & Unit of Time

8 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: patients with Crigler-Najjar disease above the age of 7 years Exclusion Criteria: cholestasis, chronic malabsorption syndrome, pregnancy

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Anja M. Hafkamp, MD

Organizational Affiliation

University Medical Center Groningen and Erasmus University Medical Center

Official's Role

Principal Investigator

First Name & Middle Initial & Last Name & Degree

Maarten Sinaasappel, MD

Organizational Affiliation

Erasmus Medical Center

Official's Role

Study Chair

First Name & Middle Initial & Last Name & Degree

Henkjan J. Verkade, MD, PhD

Organizational Affiliation

University Medical Center Groningen

Official's Role

Study Director

Facility Information:

Facility Name

Erasmus University Medical Center

City

Rotterdam

ZIP/Postal Code

3015 GJ

Country

Netherlands

12. IPD Sharing Statement

Citations:

PubMed Identifier

15726662

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. doi: 10.1002/hep.20589.

Results Reference

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PubMed Identifier

16549520

Citation

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.

Results Reference

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PubMed Identifier

14517515

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. doi: 10.1067/s0022-3476(03)00298-1.

Results Reference

background

PubMed Identifier

12378205

Citation

Verkade HJ. A novel hypothesis on the pathophysiology of neonatal jaundice. J Pediatr. 2002 Oct;141(4):594-5. No abstract available.

Results Reference

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Orlistat Treatment of Crigler-Najjar Disease

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