Hepatobiliary DiseasesNCT01200082
Sulfation of Bile Acids as a Biomarker for Hepatobiliary Diseases
An observational study of Hepatobiliary Diseases, run by University of Nebraska at 1 site in United States.
Trial summary
The investigators hypothesize that the extent of sulfation of toxic BAs and their urinary elimination can be used as a biomarker to predict the severity and prognosis of hepatobiliary diseases. Read more about this study
- Who is it for?
- Ages 19 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Hepatobiliary Diseases
- How many people
- 430 participants
- Where
- 1 siteUnited States
- Study dates
- Nov 2011to 2 Sep 2022
- 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 19 to 65 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Study population: Healthy Controls: Subjects with no apparemt hepatobiliary diseases Patient Populaton: Subjects visiting the hepatology clinic in UNMC as part of their treatment of hepatobiliry diseases
Who may be able to join
- Male or female, age 19-65, no apparent signs of hepatobiliary diseases
- Male or female, age 19-65, visiting the UNMC hepatology clinic for treatment from hepatobiliary diseases
Who cannot join
- Levels higher than 50, 56, 78 U/L for ALT, AST, and GGT, respectively.
- Patient Population
- MELD score less than 6
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Nebraska Medial Center
Omaha, Nebraska, 68198
About this study
The investigators hypothesize that the extent of sulfation of toxic BAs and their urinary elimination can be used as a biomarker to predict the severity and prognosis of hepatobiliary diseases. The investigators rationale in this project is that the discovery of biomarkers specific to liver injury would provide the foundation for a specific and non-invasive tool to evaluate disease prognosis, determine patients with higher risk of developing end-stage liver diseases, and determine patients with higher risk of recurrence of hepatobiliary complications after liver transplant.
Patients on the liver transplant list are continuously monitored during their hospitalization and are scheduled for follow-up visits for 12 months after their release post-surgery. Disease progression will be evaluated by monitoring MELD scores, survival, incidence of liver transplant, and incidence of complications related to hepatobiliary conditions such as fluid retention, GI bleeding, encephalopathy, and biliary stricture complications.
Read the detailed description
The investigators propose the following specific aims to test the investigators hypothesis:
Specific Aim #1: Establish a baseline of individual and total urinary BAs and BA-sulfates in healthy controls and patients with hepatobiliary diseases. A baseline reference of the average and distribution of the percentage of urinary BA-sulfates will be determined in healthy subjects and in patients with hepatobiliary diseases including chronic hepatitis C/B, alcoholic liver disease, hereditary, drug-induced, and autoimmune hepatobiliary diseases. The investigators working hypothesis is that patients' capability to sulfate total or specific BAs, as determined by the percentage of total or specific BAs excreted in the sulfate form, can predict the severity of hepatobiliary diseases, as determined by mayo model for end-stage liver disease (MELD) score and compensation status(compensated and decompensated). Patients with higher MELD score are considered to be at higher risk of developing severe hepatobiliary complications.
Specific Aim #2: Determine the relationship between BA sulfation and the progression of hepatobiliary diseases. This is an exploratory aim to collect preliminary data on the relationship between urinary BAs and the progression of hepatobiliary diseases in liver-transplant and non-liver-transplant patients, as monitored over a1-year period. The investigators working hypothesis is that patients' capabilities of sulfating BAs determine the progression of the disease.
- Conditions
- Hepatobiliary Diseases
- Keywords
- chronic hepatitis C/B, alcoholic liver disease, primary biliary cirrhosis, primary sclerosing cholangitis, progressive familial intrahepatic cholestasis
- Medical subject headings
- Digestive System Diseases, Liver Diseases, Alcoholic, Liver Cirrhosis, Biliary, Cholangitis, Sclerosing, Cholestasis, progressive familial intrahepatic 1
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 |
|---|---|---|
| Healthy Controls | Male or female, age 19-65, no apparent signs of hepatobiliary diseases | |
| Patients with hepatobiliary diseases | Male or female, age 19-65, visiting the UNMC hepatology clinic for treatment from hepatobiliary diseases |
What is being measured
The primary outcome is the main question the study is designed to answer.
Urinary bile acid indexes
Bile acids (BAs), the end products of cholesterol metabolism, are synthesized in liver and excreted into bile, which flows to the small intestine via the bile duct. Most of the BAs are reabsorbed from the intestine into the portal circulation and undergo enterohepatic recirculation with minimal levels detected in urine and blood under normal conditions.
Measured: Healthy controls: 4 visits over 28 days. Patients: urine collction at every visit as decided in their course of treatment
Secondary outcomes (1)
mayo model for end-stage liver disease score (MELD)
MELD score= 3.8*loge (bilirubin [mg/dL]) + 11.2*loge (INR) + 9.6*loge (creatinine [mg/dL]).
Measured: Healthy controls: 1st visit only (1 week). Patients: every time a MELD score is required by hepatologists as partrt of their regular course of treatment (1 year)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Sep 2010 (estimated)
- Study startNov 2011
- Primary completion2 Sep 2022
- Study completion2 Sep 2022
Why it stopped: Institutional Review Board approval not maintained
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Hepatobiliary DiseasesStudies of the same condition, open and under way.
- More trials run by University of NebraskaThe 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
- Cohort
- Time perspective
- Prospective
- Enrolment
- 430 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Nebraska
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Yazen M Alnouti, PhD, Principal investigator, University of Nebraska
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01200082
- Sponsor's protocol ID
- 0487-10-EP
- Status last verified
- Sep 2023
- First submitted
- 31 Aug 2010
- Last updated
- 2 Oct 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Simko V, Michael S. Urinary bile acids in population screening for inapparent liver disease. Hepatogastroenterology. 1998 Sep-Oct;45(23):1706-14.
PubMed 9840133Makino I, Hashimoto H, Shinozaki K, Yoshino K, Nakagawa S. Sulfated and nonsulfated bile acids in urine, serum, and bile of patients with hepatobiliary diseases. Gastroenterology. 1975 Mar;68(3):545-53.
PubMed 1112456Alme B, Bremmelgaard A, Sjovall J, Thomassen P. Analysis of metabolic profiles of bile acids in urine using a lipophilic anion exchanger and computerized gas-liquid chromatorgaphy-mass spectrometry. J Lipid Res. 1977 May;18(3):339-62.
PubMed 864325
Study at a glance
From the registry record, last updated by the sponsor on 2 Oct 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Sulfation of Bile Acids as a Biomarker for Hepatobiliary Diseases
- ClinicalTrials.gov ID
- NCT01200082
- Acronym / sponsor ID
- 0487-10-EP
- Conditions
- Hepatobiliary Diseases
- Keywords
- chronic hepatitis C/B, alcoholic liver disease, primary biliary cirrhosis, primary sclerosing cholangitis, progressive familial intrahepatic cholestasis
- Study type
- Observational
- Recruitment status
- TerminatedReason stopped: Institutional Review Board approval not maintained
- Enrolment
- 430 participants (actual)
- Lead sponsor
- University of NebraskaUniversity, hospital or other
- Study start
- Nov 2011 (actual)
- Primary completion
- 2 Sep 2022 (actual)
- Study completion
- 2 Sep 2022 (actual)
- First posted
- 13 Sep 2010 (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 investigators hypothesize that the extent of sulfation of toxic BAs and their urinary elimination can be used as a biomarker to predict the severity and prognosis of hepatobiliary diseases. The investigators rationale in this project is that the discovery of biomarkers specific to liver injury would provide the foundation for a specific and non-invasive tool to evaluate disease prognosis, determine patients with higher risk of developing end-stage liver diseases, and determine patients with higher risk of recurrence of hepatobiliary complications after liver transplant.
Patients on the liver transplant list are continuously monitored during their hospitalization and are scheduled for follow-up visits for 12 months after their release post-surgery. Disease progression will be evaluated by monitoring MELD scores, survival, incidence of liver transplant, and incidence of complications related to hepatobiliary conditions such as fluid retention, GI bleeding, encephalopathy, and biliary stricture complications.
Detailed description
The investigators propose the following specific aims to test the investigators hypothesis:
Specific Aim #1: Establish a baseline of individual and total urinary BAs and BA-sulfates in healthy controls and patients with hepatobiliary diseases. A baseline reference of the average and distribution of the percentage of urinary BA-sulfates will be determined in healthy subjects and in patients with hepatobiliary diseases including chronic hepatitis C/B, alcoholic liver disease, hereditary, drug-induced, and autoimmune hepatobiliary diseases. The investigators working hypothesis is that patients' capability to sulfate total or specific BAs, as determined by the percentage of total or specific BAs excreted in the sulfate form, can predict the severity of hepatobiliary diseases, as determined by mayo model for end-stage liver disease (MELD) score and compensation status(compensated and decompensated). Patients with higher MELD score are considered to be at higher risk of developing severe hepatobiliary complications.
Specific Aim #2: Determine the relationship between BA sulfation and the progression of hepatobiliary diseases. This is an exploratory aim to collect preliminary data on the relationship between urinary BAs and the progression of hepatobiliary diseases in liver-transplant and non-liver-transplant patients, as monitored over a1-year period. The investigators working hypothesis is that patients' capabilities of sulfating BAs determine the progression of the disease.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Healthy Controls | – | –Male or female, age 19-65, no apparent signs of hepatobiliary diseases |
| Patients with hepatobiliary diseases | – | –Male or female, age 19-65, visiting the UNMC hepatology clinic for treatment from hepatobiliary diseases |
Who may qualify
- Ages
- 19 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- Healthy Controls: Subjects with no apparemt hepatobiliary diseases Patient Populaton: Subjects visiting the hepatology clinic in UNMC as part of their treatment of hepatobiliry diseases
Key inclusion criteria (2 listed)
- Male or female, age 19-65, no apparent signs of hepatobiliary diseases
- Male or female, age 19-65, visiting the UNMC hepatology clinic for treatment from hepatobiliary diseases
Key exclusion criteria (3 listed)
- Levels higher than 50, 56, 78 U/L for ALT, AST, and GGT, respectively.
- Patient Population
- MELD score less than 6
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
Urinary bile acid indexes
Time frame: Healthy controls: 4 visits over 28 days. Patients: urine collction at every visit as decided in their course of treatment
Bile acids (BAs), the end products of cholesterol metabolism, are synthesized in liver and excreted into bile, which flows to the small intestine via the bile duct. Most of the BAs are reabsorbed from the intestine into the portal circulation and undergo enterohepatic recirculation with minimal levels detected in urine and blood under normal conditions.
1 secondary outcome
mayo model for end-stage liver disease score (MELD)
Time frame: Healthy controls: 1st visit only (1 week). Patients: every time a MELD score is required by hepatologists as partrt of their regular course of treatment (1 year)
Results and safety
The study was stopped early (reason given: Institutional Review Board approval not maintained). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Oct 2023.
- Background: PubMed 9840133Simko V, Michael S. Urinary bile acids in population screening for inapparent liver disease. Hepatogastroenterology. 1998 Sep-Oct;45(23):1706-14.
- Background: PubMed 1112456Makino I, Hashimoto H, Shinozaki K, Yoshino K, Nakagawa S. Sulfated and nonsulfated bile acids in urine, serum, and bile of patients with hepatobiliary diseases. Gastroenterology. 1975 Mar;68(3):545-53.
- Background: PubMed 864325Alme B, Bremmelgaard A, Sjovall J, Thomassen P. Analysis of metabolic profiles of bile acids in urine using a lipophilic anion exchanger and computerized gas-liquid chromatorgaphy-mass spectrometry. J Lipid Res. 1977 May;18(3):339-62.
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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.
Yazen M Alnouti, PhD principal investigator
University of Nebraska
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 Hepatobiliary Diseases, run by University of Nebraska 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 2 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: stopped early, as of the sponsor's last update on 2 Oct 2023. 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 stopped early (reason given: Institutional Review Board approval not maintained). Results are not available in the source record.
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?
Urinary bile acid indexes (time frame: Healthy controls: 4 visits over 28 days. Patients: urine collction at every visit as decided in their course of treatment). 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 NCT01200082, which also lists 3 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 2 Oct 2023.