Non-Alcoholic SteatohepatitisNASHNCT00677183
Development of Biomarker for Development of Non-Alcoholic Steatohepatitis (NASH) in Children
An observational study of Non-Alcoholic Steatohepatitis, run by Medical College of Wisconsin at 1 site in United States.
Trial summary
The purpose of this study is to document how often specific genotypes known to be associated with adult-onset NASH (Non-Alcoholic Steatohepatitis) occur in a pediatric cohort and investigate whether these genotypes are associated with increased susceptibility to NASH. Read more about this study
- Who is it for?
- Ages 2 to 18 years
- Conditions the study is for
- Non-Alcoholic Steatohepatitis
- How many people
- 0 participants
- Where
- 1 siteUnited States
- Study dates
- May 2008to May 2016
- Phase
- Observational
- 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 2 to 18 years
- All sexes
- No healthy volunteers
- Child, Adult
Study population: The child subjects will be recruited from the Hepatology Clinic at Children's Hospital of Wisconsin.
Who may be able to join
- All subjects aged 2-18 with biopsy proven NAFLD and/or NASH undergoing a blood draw and willing to consent to this study will qualify for inclusion in this protocol.
Who cannot join
- other causes of chronic liver disease or other chronic diseases, specifically autoimmune disorders, immunodeficiencies, or individuals with congenital/genetic disorders
- chronic viral hepatitis, Wilson's disease, or alpha -1- antitrypsin deficiency
- acute life threatening illness or conditions
Trial locations and contacts
1 site in 1 country.
United States1 site
Children's Hospital of Wisconsin
Milwaukee, Wisconsin, 53226
About this study
Official title: Development of a Biomarker for Development of Non-Alcoholic Steatohepatitis (NASH) in Children
The purpose of this study is to document how often specific genotypes known to be associated with adult-onset NASH (Non-Alcoholic Steatohepatitis) occur in a pediatric cohort and investigate whether these genotypes are associated with increased susceptibility to NASH.
Read the detailed description
NASH is a clinico-pathological entity characterized by the development of histological changes of inflammation and fibrosis in the liver that are nearly identical to those induced by excessive alcohol intake, but in the absence of alcohol abuse. Nonalcoholic steatohepatitis occurs commonly children with additional comorbidities such as obesity and diabetes mellitus. Paralleling the increasing prevalence of obesity and type 2 diabetes in the pediatric population, nonalcoholic fatty liver disease (NAFLD) and especially its more severe histological form NASH, is expected to become one of the most common causes of end-stage liver disease in both children and young adults.
Although no genome wide association studies have been conducted in association with NASH to date, individual candidate gene investigations have identified several genes associated with increase susceptibility to NASH in adults including the microsomal triglyceride transfer protein (MTP) which regulates the incorporation of triglycerides into apolipoprotein B and a key enzyme for the assembly and secretion of VLDL from hepatocytes, the manganese superoxide dismutase (MnSOD) gene which catalyzes the conversion of two molecules of superoxide anion, a highly unstable ROS, into hydrogen peroxide and oxygen more stable ROS, and lastly, phosphatidylethanolamine N-methyltransferase (PEMT) which is required for hepatic secretion of triacylglycerol in very low density lipoproteins (VLDL).
We propose the following aim:
Aim 1: To document the frequency of specific genotypes, previously identified to be associated with adult-onset NASH, in a purely pediatric cohort.
Aim 2: To investigate whether these genotypes are associated with increased susceptibility to NASH and increased occurrence of fibrosis in the cohort of pediatric subjects. Our hypothesis would be:
A significantly higher proportion of the polymorphisms would exist in those subjects with NASH compared to controls.
Aim 3: To investigate the presence of other polymorphisms or other biomarker that are indicative of pediatric NASH. Such that our secondary hypothesis would be:
Specific polymorphisms or biomarkers will be identified that will indicate a higher probability of NASH.
- Conditions
- Non-Alcoholic Steatohepatitis
- Keywords
- NASH, Biomarker
- Medical subject headings
- Non-alcoholic Fatty Liver Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| SN###.#1 | All children in this cohort will have biopsy-proven NASH. | |
| SN###.#2 | This cohort will be parents (mother and father when possible) of child subjects with biopsy-proven NASH. |
What is being measured
The primary outcome is the main question the study is designed to answer.
We will compare known frequencies from the Hapmap and specifically compare the proportions for those with NASH in adults to see if there is a difference in the child incidence of NASH.
Measured: three years
We will compare the proportions of those with NASH to those without NASH and those with fibrosis compared to those without fibrosis.
Measured: Three years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 May 2008 (estimated)
- Study startMay 2008
- Primary completionMay 2016 (estimated)
- Study completionMay 2016 (estimated)
Why it stopped: PI did not receive funding for this PI-initiated study. PI subsequently left the institution.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (9)Papers the sponsor has linked to this study.
- Other trials for Non-Alcoholic SteatohepatitisStudies of the same condition, open and under way.
- More trials run by Medical College of WisconsinThe 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
- Observational
- Observational model
- Family based
- Time perspective
- Prospective
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Medical College of Wisconsin
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Vincent F Biank, MD, Principal investigator, Medical College of Wisconsin
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00677183
- Sponsor's protocol ID
- CHW 08/36
- Other IDs
- GC 618
- Acronym
- NASH
- Status last verified
- Aug 2015
- First submitted
- 9 May 2008
- Last updated
- 25 Aug 2015
- Results posted
- No
- Data monitoring committee
- No
Publications
Angulo P, Keach JC, Batts KP, Lindor KD. Independent predictors of liver fibrosis in patients with nonalcoholic steatohepatitis. Hepatology. 1999 Dec;30(6):1356-62. doi: 10.1002/hep.510300604.
PubMed 10573511Huang BE, Amos CI, Lin DY. Detecting haplotype effects in genomewide association studies. Genet Epidemiol. 2007 Dec;31(8):803-12. doi: 10.1002/gepi.20242.
PubMed 17549762Benjamini, Y. and Hochberg, Y. 1995. Controlling the false discovery rate: A practical and powerful approach to multiple testing. J. Royal Stat. Soc. B (57): 289-300.
Breiman L, Friedman JH, Olshen RA, Stone CJ. Classification and Regression Trees. Classification and Regression Trees. 1984.
Lin DY, Zeng D, Millikan R. Maximum likelihood estimation of haplotype effects and haplotype-environment interactions in association studies. Genet Epidemiol. 2005 Dec;29(4):299-312. doi: 10.1002/gepi.20098.
PubMed 16240443Iacobellis A, Marcellini M, Andriulli A, Perri F, Leandro G, Devito R, Nobili V. Non invasive evaluation of liver fibrosis in paediatric patients with nonalcoholic steatohepatitis. World J Gastroenterol. 2006 Dec 28;12(48):7821-5. doi: 10.3748/wjg.v12.i48.7821.
PubMed 17203527Marra F. NASH: are genes blowing the hits? J Hepatol. 2004 May;40(5):853-6. doi: 10.1016/j.jhep.2004.03.005. No abstract available.
PubMed 15094235Song J, da Costa KA, Fischer LM, Kohlmeier M, Kwock L, Wang S, Zeisel SH. Polymorphism of the PEMT gene and susceptibility to nonalcoholic fatty liver disease (NAFLD). FASEB J. 2005 Aug;19(10):1266-71. doi: 10.1096/fj.04-3580com.
PubMed 16051693Marshall RJ. Partitioning methods for classification and decision making in medicine. Stat Med. 1986 Sep-Oct;5(5):517-26. doi: 10.1002/sim.4780050516.
PubMed 3538265
Study at a glance
From the registry record, last updated by the sponsor on 25 Aug 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Development of a Biomarker for Development of Non-Alcoholic Steatohepatitis (NASH) in Children
- ClinicalTrials.gov ID
- NCT00677183
- Acronym / sponsor ID
- NASH / CHW 08/36
- Conditions
- Non-Alcoholic Steatohepatitis
- Keywords
- NASH, Biomarker
- Study type
- Observational
- Recruitment status
- WithdrawnReason stopped: PI did not receive funding for this PI-initiated study. PI subsequently left the institution.
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Medical College of WisconsinUniversity, hospital or other
- Study start
- May 2008
- Primary completion
- May 2016 (estimated)
- Study completion
- May 2016 (estimated)
- First posted
- 14 May 2008 (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 is to document how often specific genotypes known to be associated with adult-onset NASH (Non-Alcoholic Steatohepatitis) occur in a pediatric cohort and investigate whether these genotypes are associated with increased susceptibility to NASH.
Detailed description
NASH is a clinico-pathological entity characterized by the development of histological changes of inflammation and fibrosis in the liver that are nearly identical to those induced by excessive alcohol intake, but in the absence of alcohol abuse. Nonalcoholic steatohepatitis occurs commonly children with additional comorbidities such as obesity and diabetes mellitus. Paralleling the increasing prevalence of obesity and type 2 diabetes in the pediatric population, nonalcoholic fatty liver disease (NAFLD) and especially its more severe histological form NASH, is expected to become one of the most common causes of end-stage liver disease in both children and young adults.
Although no genome wide association studies have been conducted in association with NASH to date, individual candidate gene investigations have identified several genes associated with increase susceptibility to NASH in adults including the microsomal triglyceride transfer protein (MTP) which regulates the incorporation of triglycerides into apolipoprotein B and a key enzyme for the assembly and secretion of VLDL from hepatocytes, the manganese superoxide dismutase (MnSOD) gene which catalyzes the conversion of two molecules of superoxide anion, a highly unstable ROS, into hydrogen peroxide and oxygen more stable ROS, and lastly, phosphatidylethanolamine N-methyltransferase (PEMT) which is required for hepatic secretion of triacylglycerol in very low density lipoproteins (VLDL).
We propose the following aim:
Aim 1: To document the frequency of specific genotypes, previously identified to be associated with adult-onset NASH, in a purely pediatric cohort.
Aim 2: To investigate whether these genotypes are associated with increased susceptibility to NASH and increased occurrence of fibrosis in the cohort of pediatric subjects. Our hypothesis would be:
A significantly higher proportion of the polymorphisms would exist in those subjects with NASH compared to controls.
Aim 3: To investigate the presence of other polymorphisms or other biomarker that are indicative of pediatric NASH. Such that our secondary hypothesis would be:
Specific polymorphisms or biomarkers will be identified that will indicate a higher probability of NASH.
Study design
- Observational model
- Family based
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| SN###.#1 | – | –All children in this cohort will have biopsy-proven NASH. |
| SN###.#2 | – | –This cohort will be parents (mother and father when possible) of child subjects with biopsy-proven NASH. |
Who may qualify
- Ages
- 2 to 18 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
- Study population
- The child subjects will be recruited from the Hepatology Clinic at Children's Hospital of Wisconsin.
Key inclusion criteria (1 listed)
- All subjects aged 2-18 with biopsy proven NAFLD and/or NASH undergoing a blood draw and willing to consent to this study will qualify for inclusion in this protocol.
Key exclusion criteria (3 listed)
- other causes of chronic liver disease or other chronic diseases, specifically autoimmune disorders, immunodeficiencies, or individuals with congenital/genetic disorders
- chronic viral hepatitis, Wilson's disease, or alpha -1- antitrypsin deficiency
- acute life threatening illness or conditions
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
We will compare known frequencies from the Hapmap and specifically compare the proportions for those with NASH in adults to see if there is a difference in the child incidence of NASH.
Time frame: three years
We will compare the proportions of those with NASH to those without NASH and those with fibrosis compared to those without fibrosis.
Time frame: Three years
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Aug 2015.
- Background: PubMed 10573511Angulo P, Keach JC, Batts KP, Lindor KD. Independent predictors of liver fibrosis in patients with nonalcoholic steatohepatitis. Hepatology. 1999 Dec;30(6):1356-62. doi: 10.1002/hep.510300604.
- Background: PubMed 17549762Huang BE, Amos CI, Lin DY. Detecting haplotype effects in genomewide association studies. Genet Epidemiol. 2007 Dec;31(8):803-12. doi: 10.1002/gepi.20242.
- BackgroundBenjamini, Y. and Hochberg, Y. 1995. Controlling the false discovery rate: A practical and powerful approach to multiple testing. J. Royal Stat. Soc. B (57): 289-300.
- BackgroundBreiman L, Friedman JH, Olshen RA, Stone CJ. Classification and Regression Trees. Classification and Regression Trees. 1984.
- Background: PubMed 16240443Lin DY, Zeng D, Millikan R. Maximum likelihood estimation of haplotype effects and haplotype-environment interactions in association studies. Genet Epidemiol. 2005 Dec;29(4):299-312. doi: 10.1002/gepi.20098.
- Background: PubMed 17203527Iacobellis A, Marcellini M, Andriulli A, Perri F, Leandro G, Devito R, Nobili V. Non invasive evaluation of liver fibrosis in paediatric patients with nonalcoholic steatohepatitis. World J Gastroenterol. 2006 Dec 28;12(48):7821-5. doi: 10.3748/wjg.v12.i48.7821.
- Background: PubMed 15094235Marra F. NASH: are genes blowing the hits? J Hepatol. 2004 May;40(5):853-6. doi: 10.1016/j.jhep.2004.03.005. No abstract available.
- Background: PubMed 16051693Song J, da Costa KA, Fischer LM, Kohlmeier M, Kwock L, Wang S, Zeisel SH. Polymorphism of the PEMT gene and susceptibility to nonalcoholic fatty liver disease (NAFLD). FASEB J. 2005 Aug;19(10):1266-71. doi: 10.1096/fj.04-3580com.
- Background: PubMed 3538265Marshall RJ. Partitioning methods for classification and decision making in medicine. Stat Med. 1986 Sep-Oct;5(5):517-26. doi: 10.1002/sim.4780050516.
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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.
Vincent F Biank, MD principal investigator
Medical College of Wisconsin
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Non-Alcoholic Steatohepatitis, run by Medical College of Wisconsin at 1 site in United States.
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 3 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: withdrawn, as of the sponsor's last update on 25 Aug 2015. 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 United States. 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 was withdrawn before enrolling participants, so there are no results.
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?
We will compare known frequencies from the Hapmap and specifically compare the proportions for those with NASH in adults to see if there is a difference in the child incidence of NASH. (time frame: three years). The study lists 2 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 NCT00677183, which also lists 9 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 25 Aug 2015.