CirrhosisNCT02400216
Deciphering the Mechanisms Involved in Microbial Translocation Across the Spectrum of HCV Associated Liver Fibrosis
An observational study of Cirrhosis, run by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) at 1 site in United States.
Trial summary
Background: Hepatitis C infection (HCV) is a leading cause of liver disease. Normal bacteria from the intestines may spread to the liver and blood during liver disease. This is called bacterial translocation (BT). Researchers think BT may cause liver disease to worsen. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Cirrhosis
- What is being tested?
- dual cholate
- How many people
- 30 participants
- Where
- 1 siteUnited States
- Study dates
- 29 May 2015to 25 Apr 2017
- 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Primary clinical patients with chronic HCV infection divided into 2 groups according to liver fibrosis stage.
Who may be able to join
- All age greater than 18 male or female
- Capacity to provide written informed consent
- Evidence of HCV RNA in 2 serum samples at least 6 months apart.
- All HCV genotypes
- Liver biopsy in the last 2 years prior to enrollment showing Ishak fibrosis score of either 0-1 or 5-6. An alternative to liver biopsy will be a Fibroscan study performed in the 6 months prior to study enrollment showing a score of either kPa <7 or above 13.
- Child-Pugh score less than or equal to 6
- Prior to each liver biopsy and portal vein cannulation procedure, blood will be drawn for CBC, PT/INR \& acute care panel.
Who cannot join
- Pregnant women or females at child bearing age not taking measures to prevent pregnancy during the period of study
- Patients currently on treatment for hepatitis C
- Clinical, serologic or histopathologic evidence supporting other etiologies of chronic liver disease besides HCV
- Current or past clinical evidence of decompensated liver disease (e.g. ascites, bleeding esophageal varices, spontaneous bacterial peritonitis, encephalopathy etc.)
- Cross sectional liver imaging study from the past 6 months showing a focal lesion suspicious of hepatocellular carcinoma and/or alpha-fetoprotein level greater than 200 ng/mL.
- Patients with active bacterial, viral or fungal, systemic or localized infection.
Show all 32Show fewer
- Antibiotic treatment 30 days prior to study enrollment
- History of chronic inflammatory diseases of the bowel (Crohn s disease, Ulcerative colitis and celiac disease)
- History of congestive heart failure of moderate to severe degree.
- History of non-cirrhotic portal hypertension or portal vein thrombosis
- Patients with severe allergic reactions to iodine contrast, which cannot be controlled by premedication with antihistamines and steroids.
- EXCLUSION CRITERIA FOR MRI:
- 12.1 Subjects with contraindication to MRI scanning. These contraindications include but are not limited to the following devices or conditions:
- <TAB>a. Implanted cardiac pacemaker or defibrillator
- <TAB>b. Cochlear Implants
- <TAB>c. Ocular foreign body (e.g. metal shavings)
- <TAB>d. Embedded shrapnel fragments
- <TAB>e. Central nervous system aneurysm clips
- <TAB>f. Implanted neural stimulator
- <TAB>g. Medical infusion pumps
- <TAB>h. Any implanted device that is incompatible with MRI.
- 12.2 Unsatisfactory performance status as judged by the referring physician such that the subject could not tolerate an MRI scan. Examples of medical conditions that would not be accepted would include unstable angina and dyspnea at rest.
- 12.3 Subjects requiring sedation for MRI studies.
- 12.4 Subjects with a condition precluding entry into the scanner (e.g. morbid obesity, claustrophobia, etc.).
- 12.5 Pregnant or lactating women.
- 12.6 Subjects with severe back-pain or motion disorders who will be unable to tolerate supine positioning within the MRI scanner and hold still for the duration of the examination.
- 12.7 For Gadolinium based and SPIO MRI Use:
- <TAB>a. History of severe allergic reaction to these contrast agents despite the use of premeditation with an anti-histaminic and cortisone.
- <TAB>b. eGFR < 60 ml/min/1.73m^2
- Absolute neutrophil count below 1000/mm^3, Hemoglobin level below 10.0 g/dl or platelet count lower than 70,000/mm^3.
- INR greater than or equal to 1.5, PTT greater than or equal to 1.3 times control and/or any known history of disease associated with increased bleeding diathesis.
- Serum creatinine greater than or equal to 2.0 mg/dl unless the measured creatinine clearance is greater than 60 mL/min
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892
About this study
Official title: A Multidisciplinary Approach to Deciphering the Mechanisms Involved In Microbial Translocation Across the Spectrum of HCV Associated Liver Fibrosis
Background:
- Hepatitis C infection (HCV) is a leading cause of liver disease. Normal bacteria from the intestines may spread to the liver and blood during liver disease. This is called bacterial translocation (BT). Researchers think BT may cause liver disease to worsen.
Read more
Objectives:
- To study the mechanisms involved in BT in early and advanced liver disease. To find out whether BT causes liver disease to worsen.
Eligibility:
- People over age 18 with HCV and clinically stable liver disease.
Design:
- Participants will be screened with medical history and physical exam. They will have blood tests and imaging studies.
- Participants will have 2 outpatient visits and a 3-day stay at the clinic.
- At visit 1, participants will have urine and blood tests. They will have a magnetic resonance imaging (MRI) scan. A solution will be injected into a vein. The MRI scanner is a metal cylinder surrounded by a magnetic field. The participant will lie on a table that slides in and out of the cylinder.
- At visit 2, a substance will be injected into a vein and swallowed. Participants will then have blood drawn 5 times over 90 minutes.
- During the inpatient stay, serial blood tests will be drawn.
- Participants will give 2 stool samples and have another MRI.
- A needle will be inserted through the chest wall into a vein inside the liver, guided by ultrasound. The blood pressure inside this vein will be measured and blood will be drawn from it. About 1 inch of liver tissue will be removed.
- A study investigator will call participants to discuss all test results.
Read the detailed description
Hepatitis C (HCV) is a leading cause of cirrhosis worldwide. Most complications associated with cirrhosis are driven by an altered portal circulation and the development of portal hypertension. Bacterial translocation (BT) from the gut to the systemic circulation is considered a pivotal mechanism contributing to the development of life-threatening complications in end stage cirrhosis. Recent evidence suggests that the liver and systemic circulation may be exposed to gut derived microbial products at earlier stages of liver disease. This early exposure may trigger hepatic inflammation, modify immune host response and accelerate hepatic fibrogenesis; which, in turn, impairs portal inflow, alters the portal circulation, and leads to development of portal hypertension. The mechanisms resulting in systemic exposure to gut derived microbial products, and the subsequent host response to BT has not been studied in patients with early liver disease nor fully compensated cirrhosis.
We therefore intend to enroll 30 chronic HCV patients with either cirrhosis (20) or minimal liver fibrosis (10). Study participants will undergo extensive evaluation with portal vein sampling and pressure measurements, dual cholate clearances, liver biopsy, serologic, immunologic, fecal microbiome and imaging studies. This will be followed by an optional second percutaneous liver biopsy and portal vein sampling 9-15 months after HCV treatment. The treatment protocol is a separate independent protocol, 15-DK- 0143 utilizing Sofosbuvir and GS-5816. The goals of our study are to characterize the extent of BT in early stages of cirrhotic and non-cirrhotic liver disease, explore the mechanisms contributing to its occurrence and identify potential serological, immunological and hemodynamic biomarkers associated with chronic infection. This, in turn, can aid in establishing a possible link between BT, subsequent host responses and severity of liver disease.
- Conditions
- Cirrhosis
- Being tested
- dual cholate
- Keywords
- Chronic Hepatitis C, Cirrhosis, Liver Biopsy, Microbiome, Natural History
- Medical subject headings
- Fibrosis, Hepatitis C, Chronic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
dual cholateDrug
test for defining disease severity
| Study group | Role | What they receive |
|---|---|---|
| Group A | Patients with fibrosis levels spanning from bridging fibrosis to cirrhosis (Ishak fibrosis score 5-6) Receives: Drug: dual cholate | |
| Group B | Patients with minimal fibrosis (Ishak score 0-1). Receives: Drug: dual cholate |
What is being measured
The primary outcome is the main question the study is designed to answer.
Microbial product detection rate
Assess the extent of BT, explore possible mechanisms accounting for its occurrence and evaluate its effects on the immune system in different stages of liver fibrosis
Measured: Before anti viral therapy and 9-15 months after treatment
Secondary outcomes (6)
Dual-cholate liver function tests
Comparison of dual-cholate liver function tests and its association with microbial product levels in portal and systemic blood, between group A and group B patients.
Measured: Baseline, and 9-15 months after treatment
SPIO-MRI Kupffer cell uptake
Comparison of SPIO-MRI Kupffer cell uptake values and its association with microbial product levels in portal and systemic blood between group A and group B patients.
Measured: Baseline, and 9-15 months after treatment
Immune activation markers
Comparison of immune activation markers to bacterial products in liver tissue between group A and group B patients before and after HCV treatment.
Measured: Baseline, and 9-15 months after treatment
Pro and anti-inflammatory gene transcription
Comparison of pro and anti-inflammatory gene transcription analysis in between group A and group B patients
Measured: Baseline, and 9-15 months after treatment
Fecal microbiome
Comparison of fecal microbiome analysis between group A and group B patients
Measured: Baseline, and 9-15 months after treatment
Species homology
Evaluation of species homology between microbial DNA identified in portal and systemic blood and fecal samples by deep sequencing.
Measured: Baseline, and 9-15 months after treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Mar 2015 (estimated)
- Study start29 May 2015
- Primary completion24 Feb 2017
- Study completion25 Apr 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for CirrhosisStudies of the same condition, open and under way.
- More trials run by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)The 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
- Case only
- Time perspective
- Cross-sectional
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Theo Heller, M.D., Principal investigator, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02400216
- Sponsor's protocol ID
- 150100
- Other IDs
- 15-DK-0100
- Status last verified
- 31 Mar 2026
- First submitted
- 26 Mar 2015
- Last updated
- 29 Oct 2026
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Oringher JL, Afruza R, Chakraborty M, Akiva KL, Zhang GY, Townsend EC, Quinn GM, Scheuing L, Menkart MG, Rai A, Kleiner DE, Levy EB, Koh C, Ali RO, Etzion O, Heller T. Portal Vein Tryptophan Pathway Analysis Reveals Gut-Mediated Inflammatory Pathway Predominance in HCV Infection. Liver Int. 2026 Apr;46(4):e70584. doi: 10.1111/liv.70584.
PubMed 41804293
Study at a glance
From the registry record, last updated by the sponsor on 29 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multidisciplinary Approach to Deciphering the Mechanisms Involved In Microbial Translocation Across the Spectrum of HCV Associated Liver Fibrosis
- ClinicalTrials.gov ID
- NCT02400216
- Acronym / sponsor ID
- 150100
- Conditions
- Cirrhosis
- Keywords
- Chronic Hepatitis C, Cirrhosis, Liver Biopsy, Microbiome, Natural History
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 30 participants (actual)
- Lead sponsor
- National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)US National Institutes of Health
- Study start
- 29 May 2015 (actual)
- Primary completion
- 24 Feb 2017 (actual)
- Study completion
- 25 Apr 2017 (actual)
- First posted
- 27 Mar 2015 (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.
Background:
- Hepatitis C infection (HCV) is a leading cause of liver disease. Normal bacteria from the intestines may spread to the liver and blood during liver disease. This is called bacterial translocation (BT). Researchers think BT may cause liver disease to worsen.
Objectives:
- To study the mechanisms involved in BT in early and advanced liver disease. To find out whether BT causes liver disease to worsen.
Eligibility:
- People over age 18 with HCV and clinically stable liver disease.
Design:
- Participants will be screened with medical history and physical exam. They will have blood tests and imaging studies.
- Participants will have 2 outpatient visits and a 3-day stay at the clinic.
- At visit 1, participants will have urine and blood tests. They will have a magnetic resonance imaging (MRI) scan. A solution will be injected into a vein. The MRI scanner is a metal cylinder surrounded by a magnetic field. The participant will lie on a table that slides in and out of the cylinder.
- At visit 2, a substance will be injected into a vein and swallowed. Participants will then have blood drawn 5 times over 90 minutes.
- During the inpatient stay, serial blood tests will be drawn.
- Participants will give 2 stool samples and have another MRI.
- A needle will be inserted through the chest wall into a vein inside the liver, guided by ultrasound. The blood pressure inside this vein will be measured and blood will be drawn from it. About 1 inch of liver tissue will be removed.
- A study investigator will call participants to discuss all test results.
Detailed description
Hepatitis C (HCV) is a leading cause of cirrhosis worldwide. Most complications associated with cirrhosis are driven by an altered portal circulation and the development of portal hypertension. Bacterial translocation (BT) from the gut to the systemic circulation is considered a pivotal mechanism contributing to the development of life-threatening complications in end stage cirrhosis. Recent evidence suggests that the liver and systemic circulation may be exposed to gut derived microbial products at earlier stages of liver disease. This early exposure may trigger hepatic inflammation, modify immune host response and accelerate hepatic fibrogenesis; which, in turn, impairs portal inflow, alters the portal circulation, and leads to development of portal hypertension. The mechanisms resulting in systemic exposure to gut derived microbial products, and the subsequent host response to BT has not been studied in patients with early liver disease nor fully compensated cirrhosis.
We therefore intend to enroll 30 chronic HCV patients with either cirrhosis (20) or minimal liver fibrosis (10). Study participants will undergo extensive evaluation with portal vein sampling and pressure measurements, dual cholate clearances, liver biopsy, serologic, immunologic, fecal microbiome and imaging studies. This will be followed by an optional second percutaneous liver biopsy and portal vein sampling 9-15 months after HCV treatment. The treatment protocol is a separate independent protocol, 15-DK- 0143 utilizing Sofosbuvir and GS-5816. The goals of our study are to characterize the extent of BT in early stages of cirrhotic and non-cirrhotic liver disease, explore the mechanisms contributing to its occurrence and identify potential serological, immunological and hemodynamic biomarkers associated with chronic infection. This, in turn, can aid in establishing a possible link between BT, subsequent host responses and severity of liver disease.
Study design
- Observational model
- Case only
- Time perspective
- Cross-sectional
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Group A | – | Drug: dual cholatePatients with fibrosis levels spanning from bridging fibrosis to cirrhosis (Ishak fibrosis score 5-6) |
| Group B | – | Drug: dual cholatePatients with minimal fibrosis (Ishak score 0-1). |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Primary clinical patients with chronic HCV infection divided into 2 groups according to liver fibrosis stage.
Key inclusion criteria (7 listed)
Key exclusion criteria (32 listed)
- Pregnant women or females at child bearing age not taking measures to prevent pregnancy during the period of study
- Patients currently on treatment for hepatitis C
- Clinical, serologic or histopathologic evidence supporting other etiologies of chronic liver disease besides HCV
- Current or past clinical evidence of decompensated liver disease (e.g. ascites, bleeding esophageal varices, spontaneous bacterial peritonitis, encephalopathy etc.)
- Cross sectional liver imaging study from the past 6 months showing a focal lesion suspicious of hepatocellular carcinoma and/or alpha-fetoprotein level greater than 200 ng/mL.
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 |
|---|---|---|
| dual cholatetest for defining disease severity | Drug | Group A, Group B |
Primary outcome
Microbial product detection rate
Time frame: Before anti viral therapy and 9-15 months after treatment
Assess the extent of BT, explore possible mechanisms accounting for its occurrence and evaluate its effects on the immune system in different stages of liver fibrosis
6 secondary outcomes
Dual-cholate liver function tests
Time frame: Baseline, and 9-15 months after treatment
SPIO-MRI Kupffer cell uptake
Time frame: Baseline, and 9-15 months after treatment
Immune activation markers
Time frame: Baseline, and 9-15 months after treatment
Pro and anti-inflammatory gene transcription
Time frame: Baseline, and 9-15 months after treatment
Fecal microbiome
Time frame: Baseline, and 9-15 months after treatment
Species homology
Time frame: Baseline, and 9-15 months after treatment
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 29 Oct 2026.
- Derived from this study: PubMed 41804293Oringher JL, Afruza R, Chakraborty M, Akiva KL, Zhang GY, Townsend EC, Quinn GM, Scheuing L, Menkart MG, Rai A, Kleiner DE, Levy EB, Koh C, Ali RO, Etzion O, Heller T. Portal Vein Tryptophan Pathway Analysis Reveals Gut-Mediated Inflammatory Pathway Predominance in HCV Infection. Liver Int. 2026 Apr;46(4):e70584. doi: 10.1111/liv.70584.
- NIH Clinical Center Detailed Web PageLink provided by the sponsor.
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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.
Theo Heller, M.D. principal investigator
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
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 Cirrhosis, run by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) 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 7 inclusion and 32 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 29 Oct 2026. 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 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?
Microbial product detection rate (time frame: Before anti viral therapy and 9-15 months after 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 NCT02400216, which also lists 1 linked publication.
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 29 Oct 2026.