Hepatitis C, ChronicReproNCT01579162
Intra-Individual Reproducibility of the Non-Invasive Assessment of the Portal Circulation
A study testing Cholate-24-13C (IND 65121) & Cholate-2,2,4,4-d4 (IND 65123) in people with Hepatitis C, Chronic and Non-Alcoholic Fatty Liver Disease, run by HepQuant, LLC at 1 site in United States.
Trial summary
HepQuant tests are new liver tests that are being developed to accurately measure liver function with sensitivity and specificity while being safe and non-invasive. The primary goal of this study is to define the intra-individual reproducibility of the HepQuant tests, that is, to see if a person is given the tests… Read more about this study
- Who is it for?
- Ages 22 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Hepatitis C, Chronic, Non-Alcoholic Fatty Liver Disease
- What is being tested?
- Cholate-24-13C (IND 65121) & Cholate-2,2,4,4-d4 (IND 65123)
- Type of treatment
- Pill or oral medicine, Injection or infusion, Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 48 participants
- Where
- 1 siteUnited States
- Study dates
- Jan 2012to Apr 2015
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 22 to 65 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Diagnosis of chronic HCV or NASH
- Liver biopsy within 2 years of enrollment
- Compensated liver disease
Who cannot join
- Decompensated liver disease
- Currently being treated with beta blockers, ACE inhibitors, or other agents affecting FMD
- Malignancy diagnosed within 5 years of study enrollment without demonstrated clearance
- History of congestive heart failure
- Renal insufficiency with chronic kidney disease stage 4 or 5 (GFR < 30 mL/min/1.73m2)
- Crohn's disease or any active intestinal inflammatory condition
Show all 10Show fewer
- Having an ileal resection
- Diabetic Gastroparesis
- Pregnancy or intent to become pregnant. Urine pregnancy tests will be performed at each visit.
- Inability to consent for one's self
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Colorado Hospital
Aurora, Colorado, 80045
About this study
HepQuant tests are new liver tests that are being developed to accurately measure liver function with sensitivity and specificity while being safe and non-invasive. The primary goal of this study is to define the intra-individual reproducibility of the HepQuant tests, that is, to see if a person is given the tests several times that the test results are essentially the same each time. Subjects for this study will include healthy controls and patients with chronic liver diseases. The chronic liver diseases will include hepatitis C virus (HCV) infection and a serious form of fatty liver disease, known as non-alcoholic steatohepatitis (NASH). The HCV and NASH patients will include men and women, and those with early stage and late stage liver disease as defined by the amount of fibrosis observed in their liver biopsies. Once a subject has been enrolled in the study they will be given the HepQuant tests on three separate days within the span of one month. The hypothesis of this study is that HepQuant tests will reproducibly report liver function in healthy controls and patients with all stages of chronic HCV and NASH liver disease and that liver function will decrease as the amount of liver fibrosis increases in the chronic liver disease patients.
- Being tested
- Cholate-24-13C (IND 65121) & Cholate-2,2,4,4-d4 (IND 65123)
- Keywords
- Hepatitis, Fatty Liver
- Medical subject headings
- Hepatitis C, Chronic, Non-alcoholic Fatty Liver Disease, Hepatitis, Fatty Liver
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Cholate-24-13C (IND 65121) & Cholate-2,2,4,4-d4 (IND 65123)Device
Also called Cholic acid-24-13C, Cholic acid-2,2,4,4-d4
The FDA has indicated that liver function diagnostic testing with stable isotope labeled cholates would be considered a drug/device combination product. The drugs administered at each test visit will be:
20 mg Cholate-24-13C, IV (in the vein), dissolved in NaHCO3 and mixed with albumin.
40 mg Cholate-2,2,4,4-d4, oral, dissolved in NaHCO3 and mixed with juice.
The 3 test visits will be on separate days within a span of 30 days
| Study group | Role | What they receive |
|---|---|---|
| Healthy Controls | Experimental | Healthy controls will be recruited to have approximately equal numbers of men and women. Controls will be of healthy weight as defined by a BMI 18-25 and without liver disease or risk factors for liver disease. Receives: Device: Cholate-24-13C (IND 65121) & Cholate-2,2,4,4-d4 (IND 65123) |
| chronic HCV patients with F0-F2 fibrosis | Experimental | Not described Receives: Device: Cholate-24-13C (IND 65121) & Cholate-2,2,4,4-d4 (IND 65123) |
| chronic HCV patients with F3-F4 fibrosis | Experimental | Not described Receives: Device: Cholate-24-13C (IND 65121) & Cholate-2,2,4,4-d4 (IND 65123) |
| NASH patients with F0-F2 fibrosis | Experimental | Not described Receives: Device: Cholate-24-13C (IND 65121) & Cholate-2,2,4,4-d4 (IND 65123) |
| NASH patients with F3-F4 fibrosis | Experimental | Not described Receives: Device: Cholate-24-13C (IND 65121) & Cholate-2,2,4,4-d4 (IND 65123) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Cholate Shunt Test
The Cholate Shunt Test result is defined as the ratio of the IV Cholate Clearance to the Oral Cholate Clearance and is expressed as a percentage. The higher the SHUNT percentage, the more the blood flow is shunting around the liver, the more severe the liver disease.
The average of the SHUNT test results (ratio of IV Cholate Clearance to Oral Cholate Clearance) from all three time points (3 visits within 30 days) for each participant was used in the calculation of the group SHUNT Test results.
Measured: Average of all three study visits performed within 30 days
Secondary outcomes (2)
Intra-individual Reproducibility of the Cholate SHUNT Test Across All Subjects
The intra-individual reproducibility of the Cholate Shunt Test (SHUNT %), will be defined by its average Coefficient of Variation (CV) and its Intra-Class Correlation (ICC). Each subject will be tested at baseline and then twice more on separate days within the span of one month. The CV of each subject's three replicate tests will be used to calculate the average CV for each type of test. All test results for each type of test will be used to calculate its ICC.
Measured: All three study visits within 30 days
Intra-class Reproducibility of the Disease Severity Index (DSI) by Histological Fibrosis Stage
The intra-class correlation coefficients (ICCs) for reproducibility of the Disease Severity Index (DSI, an index value measuring severity of liver disease that can be calculated using the SHUNT Test results) were obtained by stage of liver fibrosis by liver biopsy.
The DSI is a score on a scale from 0 (healthy) to 50 (severe liver disease), so the higher the DSI, the more severe the liver disease. Fibrosis scores increase with disease severity as well, so subjects with F0-F2 fibrosis have less severe liver disease than subjects with F3-F4 fibrosis.
Measured: Average of DSIs obtained from all three study visits within 30 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Apr 2012 (estimated)
- Study startJan 2012
- Primary completionApr 2015
- Study completionApr 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Hepatitis C, ChronicStudies of the same condition, open and under way.
- 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
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 48 participants (actual)
Sponsor and investigators
- Lead sponsor
- HepQuant, LLC
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- James R Burton, MD, Principal investigator, University of Colorado School of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01579162
- Sponsor's protocol ID
- HepQuant-001
- Acronym
- Repro
- Status last verified
- Jun 2021
- First submitted
- 9 Feb 2012
- Last updated
- 15 Jul 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Everson GT, Shiffman ML, Hoefs JC, Morgan TR, Sterling RK, Wagner DA, Lauriski S, Curto TM, Stoddard A, Wright EC; HALT-C Trial Group. Quantitative liver function tests improve the prediction of clinical outcomes in chronic hepatitis C: results from the Hepatitis C Antiviral Long-term Treatment Against Cirrhosis Trial. Hepatology. 2012 Apr;55(4):1019-29. doi: 10.1002/hep.24752. Epub 2012 Mar 1.
PubMed 22030902Everson GT, Shiffman ML, Hoefs JC, Morgan TR, Sterling RK, Wagner DA, Desanto JL, Curto TM, Wright EC; HALT-C Trial Group. Quantitative tests of liver function measure hepatic improvement after sustained virological response: results from the HALT-C trial. Aliment Pharmacol Ther. 2009 Mar 1;29(5):589-601. doi: 10.1111/j.1365-2036.2008.03908.x. Epub 2008 Dec 1.
PubMed 19053983Everson GT, Shiffman ML, Morgan TR, Hoefs JC, Sterling RK, Wagner DA, Kulig CC, Curto TM, Wright EC; Halt-C Trial Group. The spectrum of hepatic functional impairment in compensated chronic hepatitis C: results from the Hepatitis C Anti-viral Long-term Treatment against Cirrhosis Trial. Aliment Pharmacol Ther. 2008 May;27(9):798-809. doi: 10.1111/j.1365-2036.2008.03639.x. Epub 2008 Feb 7.
PubMed 18266997Everson GT, Martucci MA, Shiffman ML, Sterling RK, Morgan TR, Hoefs JC; HALT-C trial group. Portal-systemic shunting in patients with fibrosis or cirrhosis due to chronic hepatitis C: the minimal model for measuring cholate clearances and shunt. Aliment Pharmacol Ther. 2007 Aug 1;26(3):401-10. doi: 10.1111/j.1365-2036.2007.03389.x.
PubMed 17635375
Study at a glance
From the registry record, last updated by the sponsor on 15 Jul 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Intra-Individual Reproducibility of the Non-Invasive Assessment of the Portal Circulation
- ClinicalTrials.gov ID
- NCT01579162
- Acronym / sponsor ID
- Repro / HepQuant-001
- Keywords
- Hepatitis, Fatty Liver
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 48 participants (actual)
- Lead sponsor
- HepQuant, LLCIndustry (pharma, biotech, devices)
- Study start
- Jan 2012
- Primary completion
- Apr 2015 (actual)
- Study completion
- Apr 2015 (actual)
- First posted
- 17 Apr 2012 (estimated)
- Results
- Posted 15 Jul 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
HepQuant tests are new liver tests that are being developed to accurately measure liver function with sensitivity and specificity while being safe and non-invasive. The primary goal of this study is to define the intra-individual reproducibility of the HepQuant tests, that is, to see if a person is given the tests several times that the test results are essentially the same each time. Subjects for this study will include healthy controls and patients with chronic liver diseases. The chronic liver diseases will include hepatitis C virus (HCV) infection and a serious form of fatty liver disease, known as non-alcoholic steatohepatitis (NASH). The HCV and NASH patients will include men and women, and those with early stage and late stage liver disease as defined by the amount of fibrosis observed in their liver biopsies. Once a subject has been enrolled in the study they will be given the HepQuant tests on three separate days within the span of one month. The hypothesis of this study is that HepQuant tests will reproducibly report liver function in healthy controls and patients with all stages of chronic HCV and NASH liver disease and that liver function will decrease as the amount of liver fibrosis increases in the chronic liver disease patients.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| Healthy Controls | Experimental | Device: Cholate-24-13C (IND 65121) & Cholate-2,2,4,4-d4 (IND 65123)Healthy controls will be recruited to have approximately equal numbers of men and women. Controls will be of healthy weight as defined by a BMI 18-25 and without liver disease or risk factors for liver disease. |
| chronic HCV patients with F0-F2 fibrosis | Experimental | Device: Cholate-24-13C (IND 65121) & Cholate-2,2,4,4-d4 (IND 65123) |
| chronic HCV patients with F3-F4 fibrosis | Experimental | Device: Cholate-24-13C (IND 65121) & Cholate-2,2,4,4-d4 (IND 65123) |
| NASH patients with F0-F2 fibrosis | Experimental | Device: Cholate-24-13C (IND 65121) & Cholate-2,2,4,4-d4 (IND 65123) |
| NASH patients with F3-F4 fibrosis | Experimental | Device: Cholate-24-13C (IND 65121) & Cholate-2,2,4,4-d4 (IND 65123) |
Who may qualify
- Ages
- 22 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Diagnosis of chronic HCV or NASH
- Liver biopsy within 2 years of enrollment
- Compensated liver disease
Key exclusion criteria (10 listed)
- Decompensated liver disease
- Currently being treated with beta blockers, ACE inhibitors, or other agents affecting FMD
- Malignancy diagnosed within 5 years of study enrollment without demonstrated clearance
- History of congestive heart failure
- Renal insufficiency with chronic kidney disease stage 4 or 5 (GFR < 30 mL/min/1.73m2)
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 |
|---|---|---|
| Cholate-24-13C (IND 65121) & Cholate-2,2,4,4-d4 (IND 65123)Also: Cholic acid-24-13C, Cholic acid-2,2,4,4-d4The FDA has indicated that liver function diagnostic testing with stable isotope labeled cholates would be considered a drug/device combination product. The drugs administered at each test visit will be: 20 mg Cholate-24-13C, IV (in the vein), dissolved in NaHCO3 and mixed with albumin. 40 mg Cholate-2,2,4,4-d4, oral, dissolved in NaHCO3 and mixed with juice. The 3 test visits will be on separate days within a span of 30 days | Device | Healthy Controls, NASH patients with F0-F2 fibrosis, NASH patients with F3-F4 fibrosis, chronic HCV patients with F0-F2 fibrosis, chronic HCV patients with F3-F4 fibrosis |
Primary outcome
Cholate Shunt Test
Time frame: Average of all three study visits performed within 30 days
The Cholate Shunt Test result is defined as the ratio of the IV Cholate Clearance to the Oral Cholate Clearance and is expressed as a percentage. The higher the SHUNT percentage, the more the blood flow is shunting around the liver, the more severe the liver disease. The average of the SHUNT test results (ratio of IV Cholate Clearance to Oral Cholate Clearance) from all three time points (3 visits within 30 days) for each participant was used in the calculation of the group SHUNT Test results.
2 secondary outcomes
Intra-individual Reproducibility of the Cholate SHUNT Test Across All Subjects
Time frame: All three study visits within 30 days
Intra-class Reproducibility of the Disease Severity Index (DSI) by Histological Fibrosis Stage
Time frame: Average of DSIs obtained from all three study visits within 30 days
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Jul 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 22030902Everson GT, Shiffman ML, Hoefs JC, Morgan TR, Sterling RK, Wagner DA, Lauriski S, Curto TM, Stoddard A, Wright EC; HALT-C Trial Group. Quantitative liver function tests improve the prediction of clinical outcomes in chronic hepatitis C: results from the Hepatitis C Antiviral Long-term Treatment Against Cirrhosis Trial. Hepatology. 2012 Apr;55(4):1019-29. doi: 10.1002/hep.24752. Epub 2012 Mar 1.
- Background: PubMed 19053983Everson GT, Shiffman ML, Hoefs JC, Morgan TR, Sterling RK, Wagner DA, Desanto JL, Curto TM, Wright EC; HALT-C Trial Group. Quantitative tests of liver function measure hepatic improvement after sustained virological response: results from the HALT-C trial. Aliment Pharmacol Ther. 2009 Mar 1;29(5):589-601. doi: 10.1111/j.1365-2036.2008.03908.x. Epub 2008 Dec 1.
- Background: PubMed 18266997Everson GT, Shiffman ML, Morgan TR, Hoefs JC, Sterling RK, Wagner DA, Kulig CC, Curto TM, Wright EC; Halt-C Trial Group. The spectrum of hepatic functional impairment in compensated chronic hepatitis C: results from the Hepatitis C Anti-viral Long-term Treatment against Cirrhosis Trial. Aliment Pharmacol Ther. 2008 May;27(9):798-809. doi: 10.1111/j.1365-2036.2008.03639.x. Epub 2008 Feb 7.
- Background: PubMed 17635375Everson GT, Martucci MA, Shiffman ML, Sterling RK, Morgan TR, Hoefs JC; HALT-C trial group. Portal-systemic shunting in patients with fibrosis or cirrhosis due to chronic hepatitis C: the minimal model for measuring cholate clearances and shunt. Aliment Pharmacol Ther. 2007 Aug 1;26(3):401-10. doi: 10.1111/j.1365-2036.2007.03389.x.
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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.
James R Burton, MD principal investigator
University of Colorado School of Medicine
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Cholate-24-13C (IND 65121) & Cholate-2,2,4,4-d4 (IND 65123) in people with Hepatitis C, Chronic and Non-Alcoholic Fatty Liver Disease, run by HepQuant, LLC 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 3 inclusion and 10 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 15 Jul 2021. 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?
Yes. Results are posted in the registry (first posted 15 Jul 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Cholate Shunt Test (time frame: Average of all three study visits performed within 30 days). 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 NCT01579162, 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 15 Jul 2021.