Intra-Individual Reproducibility of the Non-Invasive Assessment of the Portal Circulation

This study is currently recruiting participants. (see Contacts and Locations)
Verified February 2014 by HepQuant, LLC
Sponsor:
Information provided by (Responsible Party):
HepQuant, LLC
ClinicalTrials.gov Identifier:
NCT01579162
First received: February 9, 2012
Last updated: February 14, 2014
Last verified: February 2014
  Purpose

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.


Condition Intervention
Hepatitis C, Chronic
Non-Alcoholic Fatty Liver Disease
Device: Cholate-24-13C (IND 65121) & Cholate-2,2,4,4-d4 (IND 65123)

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Diagnostic
Official Title: Intra-Individual Reproducibility of the Non-Invasive Assessment of the Portal Circulation

Resource links provided by NLM:


Further study details as provided by HepQuant, LLC:

Primary Outcome Measures:
  • Cholate Shunt Test [ Time Frame: 9 months ] [ Designated as safety issue: No ]
    The Cholate Shunt Test result is defined as the ratio of the IV Cholate Clearance Test result to the Oral Cholate Clearance Test result and is expressed as a percentage. The IV Cholate Clearance Test result = (dose cholate-24-13C/AUC cholate-24-13C)/subject weight and is expressed as mL/min/kg. The Oral Cholate Clearance Test result = (dose cholate-2,2,4,4-d4/AUC cholate-2,2,4,4-d4)/subject weight and is expressed as mL/min/kg. The AUC cholate-24-13C and AUC cholate-2,2,4,4-d4 are calculated from LCMS analysis of serum samples collected at 0, 5, 20, 45, 60, 90 minutes post-dose.


Secondary Outcome Measures:
  • Intra-individual Reproducibility of the Cholate Tests [ Time Frame: 9 months ] [ Designated as safety issue: No ]
    The intra-individual reproducibility of each cholate test, the IV Cholate Clearance Test, the Oral Cholate Clearance Test, and the Cholate Shunt Test, 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.

  • Correlation of Cholate Tests with Histological Fibrosis Stage [ Time Frame: 9 months ] [ Designated as safety issue: No ]
    The correlation of each of the cholate test results with the histological fibrosis stage in chronic HCV patients will be determined by Pearson correlations and expressed by p values and r2 values. The correlation of the cholate test results with the histological fibrosis stage in NASH patients will be determined in the same manner.


Estimated Enrollment: 40
Study Start Date: January 2012
Estimated Study Completion Date: October 2014
Estimated Primary Completion Date: July 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Healthy Controls
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.
Device: Cholate-24-13C (IND 65121) & Cholate-2,2,4,4-d4 (IND 65123)

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

Other Names:
  • Cholic acid-24-13C
  • Cholic acid-2,2,4,4-d4
Experimental: chronic HCV patients with F0-F2 fibrosis Device: Cholate-24-13C (IND 65121) & Cholate-2,2,4,4-d4 (IND 65123)

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

Other Names:
  • Cholic acid-24-13C
  • Cholic acid-2,2,4,4-d4
Experimental: chronic HCV patients with F3-F4 fibrosis Device: Cholate-24-13C (IND 65121) & Cholate-2,2,4,4-d4 (IND 65123)

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

Other Names:
  • Cholic acid-24-13C
  • Cholic acid-2,2,4,4-d4
Experimental: NASH patients with F0-F2 fibrosis Device: Cholate-24-13C (IND 65121) & Cholate-2,2,4,4-d4 (IND 65123)

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

Other Names:
  • Cholic acid-24-13C
  • Cholic acid-2,2,4,4-d4
Experimental: NASH patients with F3-F4 fibrosis Device: Cholate-24-13C (IND 65121) & Cholate-2,2,4,4-d4 (IND 65123)

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

Other Names:
  • Cholic acid-24-13C
  • Cholic acid-2,2,4,4-d4

  Eligibility

Ages Eligible for Study:   22 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Diagnosis of chronic HCV or NASH
  • Liver biopsy within 2 years of enrollment
  • Compensated liver disease

Exclusion Criteria:

  • 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
  • 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01579162

Contacts
Contact: Michael Cookson 303-724-1876 Michael.Cookson@UCDenver.edu
Contact: Jennifer L DeSanto, RN 303-724-1861 Jennifer.DeSanto@UCDenver.edu

Locations
United States, Colorado
University of Colorado Hospital Recruiting
Aurora, Colorado, United States, 80045
Contact: Michael Cookson    303-724-1876    Michael.Cookson@UCDenver.edu   
Contact: Jennifer L DeSanto, RN    303-724-1861    Jennifer.Desanto@UCDenver.edu   
Principal Investigator: James R Burton, MD         
Sponsors and Collaborators
HepQuant, LLC
Investigators
Principal Investigator: James R Burton, MD University of Colorado School of Medicine
  More Information

Publications:
Responsible Party: HepQuant, LLC
ClinicalTrials.gov Identifier: NCT01579162     History of Changes
Other Study ID Numbers: HepQuant-001
Study First Received: February 9, 2012
Last Updated: February 14, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by HepQuant, LLC:
Hepatitis
Fatty Liver

Additional relevant MeSH terms:
Fatty Liver
Hepatitis
Hepatitis A
Hepatitis C
Liver Diseases
Hepatitis C, Chronic
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Flaviviridae Infections
Hepatitis, Chronic
Cholic Acids
Gastrointestinal Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on August 18, 2014