Crigler-Najjar SyndromeNCT00461799
Orlistat Treatment of Crigler-Najjar Disease
A study testing orlistat in people with Crigler-Najjar Syndrome, run by University Medical Center Groningen at 1 site in Netherlands.
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. Read more about this study
- Who is it for?
- Ages 8 years and older
- Conditions the study is for
- Crigler-Najjar Syndrome
- What is being tested?
- orlistat
- How many people
- 16 participants
- Where
- 1 siteNetherlands
- Study dates
- Sep 2003to Jan 2004
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 8 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- patients with Crigler-Najjar disease above the age of 7 years
Who cannot join
- cholestasis, chronic malabsorption syndrome, pregnancy
Trial locations and contacts
1 site in 1 country.
About this study
Official title: 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.
Read the 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.
- Conditions
- Crigler-Najjar Syndrome
- Being tested
- orlistat
- Keywords
- Crigler-Najjar disease., Bilirubin., Phototherapy., Orlistat., Unconjugated hyperbilirubinemia.
- Medical subject headings
- Crigler-Najjar Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
orlistatDrug
What is being measured
The primary outcome is the main question the study is designed to answer.
decrease in plasma unconjugated bilirubin level during orlistat
increase in fecal fat excretion during orlistat
increase in fecal bilirubin concentration during orlistat
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Apr 2007 (estimated)
- Study startSep 2003
- Study completionJan 2004
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Crigler-Najjar SyndromeStudies of the same condition, open and under way.
- More trials run by University Medical Center GroningenThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind
- Enrolment
- 16 participants
Sponsor and investigators
- Lead sponsor
- University Medical Center Groningen
- Sponsor type
- University, hospital or other
- Collaborators
- Erasmus Medical Center, De Najjar Stichting
- Investigators
- Anja M. Hafkamp, MD, Principal investigator, University Medical Center Groningen and Erasmus University Medical CenterMaarten Sinaasappel, MD, Study chair, Erasmus Medical CenterHenkjan J. Verkade, MD, PhD, Study director, University Medical Center Groningen
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00461799
- Sponsor's protocol ID
- CN-01
- Status last verified
- Apr 2007
- First submitted
- 16 Apr 2007
- Last updated
- 18 Apr 2007
- Results posted
- No
- Data monitoring committee
- No
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.
PubMed 15726662Hafkamp 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.
PubMed 16549520Nishioka 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.
PubMed 14517515Verkade HJ. A novel hypothesis on the pathophysiology of neonatal jaundice. J Pediatr. 2002 Oct;141(4):594-5. No abstract available.
PubMed 12378205
Study at a glance
From the registry record, last updated by the sponsor on 18 Apr 2007. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Orlistat Treatment of Unconjugated Hyperbilirubinemia in Crigler-Najjar Disease; A Randomized Controlled Trial
- ClinicalTrials.gov ID
- NCT00461799
- Acronym / sponsor ID
- CN-01
- Conditions
- Crigler-Najjar Syndrome
- Keywords
- Crigler-Najjar disease., Bilirubin., Phototherapy., Orlistat., Unconjugated hyperbilirubinemia.
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 16 participants
- Lead sponsor
- University Medical Center GroningenUniversity, hospital or other
- Collaborators
- Erasmus Medical Center, De Najjar Stichting
- Study start
- Sep 2003
- Study completion
- Jan 2004 (actual)
- First posted
- 18 Apr 2007 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind
Who may qualify
- Ages
- 8 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (1 listed)
- patients with Crigler-Najjar disease above the age of 7 years
Key exclusion criteria (1 listed)
- cholestasis, chronic malabsorption syndrome, pregnancy
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| orlistat | Drug | – |
Primary outcome
decrease in plasma unconjugated bilirubin level during orlistat
increase in fecal fat excretion during orlistat
increase in fecal bilirubin concentration during orlistat
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Apr 2007.
- Background: PubMed 15726662Hafkamp 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.
- Background: PubMed 16549520Hafkamp 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.
- Background: PubMed 14517515Nishioka 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.
- Background: PubMed 12378205Verkade HJ. A novel hypothesis on the pathophysiology of neonatal jaundice. J Pediatr. 2002 Oct;141(4):594-5. No abstract available.
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RecruitingPhase 1/2
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RecruitingPhase 2
Efficacy and Safety of GNT0003 Following Imlifidase Pre-treatment in Severe Crigler-Najjar Syndrome
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Recruiting
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Anja M. Hafkamp, MD principal investigator
University Medical Center Groningen and Erasmus University Medical Center
Maarten Sinaasappel, MD study chair
Erasmus Medical Center
Henkjan J. Verkade, MD, PhD study director
University Medical Center Groningen
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing orlistat in people with Crigler-Najjar Syndrome, run by University Medical Center Groningen at 1 site in Netherlands.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 18 Apr 2007. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
decrease in plasma unconjugated bilirubin level during orlistat. The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00461799, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Apr 2007.