Liver CirrhosisNCT01951209
Pilot Study Of The Effect Of Rifaximin On B-Cell Dysregulation In Cirrhosis
A study testing Rifaximin in people with Liver Cirrhosis and Chronic Hepatitis C, run by David E. Kaplan, MD MSc at 1 site in United States.
Trial summary
Hepatitis C is the leading cause of chronic liver disease and cirrhosis in United States veterans. Cirrhosis is associated with impaired antibody responses and increased risk of bacterial infections. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Liver Cirrhosis, Chronic Hepatitis C
- What is being tested?
- Rifaximin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 13 participants
- Where
- 1 siteUnited States
- Study dates
- 17 Nov 2016to 12 Jun 2017
- Phase
- Interventional
- 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 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Current or prior chronic Hepatitis C infection as documented by detectable HCV RNA in prior 5 years
- Child-Turcotte-Pugh stage A5-B8. Cirrhosis diagnosis may be based on either histological criteria (an previous liver biopsy showing F4/4 or F5-6/6 fibrosis) or clinical criteria (nodular liver on abdominal imaging, splenomegaly, thrombocytopenia, spider telangiectasias, palmar erythema, ascites, varices).
- Platelet count < 175,000/ul
- Subject capable of giving informed consent
Who cannot join
- Active alcohol use > 20g/d
- Current or planned (within following 6 months) antiviral therapy for hepatitis C
- HIV co-infection
- Diagnosis of overt hepatic encephalopathy
- Current lactulose use
- Exposure to rifaximin, rifampin or rifabutin within 12 months
Show all 17Show fewer
- History of C. difficile colitis
- History of adverse drug reaction or sensitivity to rifaximin, rifampin or rifabutin or any inactive components of rifaximin
- Pregnancy
- Anemia with hemoglobin < 10g/dl or hematocrit < 30%
- Chronic kidney disease with creatinine > 2.1mg/dl
- Total bilirubin > 3.0g/dl
- Active non-hepatic medical conditions such as congestive heart failure, chronic lung disease requiring oxygen, coronary artery disease with unstable angina
- Requirement for chronic immunosuppressive therapy such as corticosteroids, cyclophosphamide, azathioprine, TNF-alpha antagonists
- Chronic autoimmune diseases such as systemic lupus erythematosus and rheumatoid arthritis
- Post-liver transplantation status or anticipated liver transplantation within 6 months.
- Systemic antimicrobial exposure within 30 days of planned Visit 1
Trial locations and contacts
1 site in 1 country.
United States1 site
Philadelphia VA Medical Center
Philadelphia, Pennsylvania, 19104
About this study
Official title: Prospective Pilot Study of the Effect of Rifaximin on B-Cell Dysregulation in Cirrhosis Due to Chronic Hepatitis C Infection
Hepatitis C is the leading cause of chronic liver disease and cirrhosis in United States veterans. Cirrhosis is associated with impaired antibody responses and increased risk of bacterial infections. We have recently identified that cirrhosis is associated with abnormalities of memory B-cells, cells that make antibodies and help protect against bacterial infections. We have identified that chemicals associated with gut bacteria might play a role in causing these B-cell abnormalities. It is well known that gut bacteria have increased access to the blood in individuals with cirrhosis, a process called bacterial translocation. We hypothesize that reducing bacteria counts in the gut by using poorly-absorbed antibiotics (also known as selective gut decontamination) will partially reverse losses of memory B-cells in cirrhosis by reducing bacterial translocation.
Read the detailed description
We intend to enroll 18 patients with cirrhosis who do not have hepatic encephalopathy to prospectively evaluate the impact of rifaximin on B-cell phenotype and function. We plan to employ a randomized, double-masked, prospective crossover design to minimize bias. Subjects will be randomized to receive either rifaximin SSD 80mg or a matched placebo once daily for 12 weeks then crossed over to opposite therapy for 12 weeks. Serum and lymphocytes will be collected at baseline and every 4 weeks for in vitro assessment markers of gut microbial translocation and B-cell assays. Stool will be collected at baseline and every 12 weeks for future evaluation of changes of the gut microbiome.
- Conditions
- Liver Cirrhosis, Chronic Hepatitis C
- Being tested
- Rifaximin, Placebo
- Keywords
- Human, Hepatitis C, Cirrhosis, B-cell, Rifaximin
- Medical subject headings
- Liver Cirrhosis, Hepatitis C, Chronic, Hepatitis C, Fibrosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RifaximinDrug
Also called Rifaximin (Xifaxan)
550mg orally twice daily for 12 weeks
PlaceboDrug
Matched placebo
| Study group | Role | What they receive |
|---|---|---|
| Rifaximin/Placebo | Experimental | Rifaximin 550mg po bid for 12 weeks followed by crossover to matched placebo po bid x 12 weeks Receives: Drug: Rifaximin; Drug: Placebo |
| Placebo/Rifaximin SSD | Experimental | Matched placebo po bid for 12 weeks followed by crossover to Rifaximin 550mg po bid x 12 weeks Receives: Drug: Rifaximin; Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in CD27+ B-cell frequency
Measured: Week 0 (Baseline) to Week 12
Secondary outcomes (1)
Change in basal B-cell activation
5 x 104/well B-cells negatively selected from normal donor PBMC will be cultured in 50% RPMI 1640/50% cirrhotic patient serum for 48 hours. After 48 hours, B-cells will be assessed for activation markers such as HLA-DR geometric mean fluorescence intensity.
Measured: Week 0 to Week 12
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Sep 2013 (estimated)
- Study start17 Nov 2016
- Primary completion17 Nov 2016
- Study completion12 Jun 2017
Why it stopped: Inadequate enrollment prior to expiration date of unreplaceable blinded investigational product
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 Liver CirrhosisStudies 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
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 13 participants (actual)
Sponsor and investigators
- Lead sponsor
- David E. Kaplan, MD MSc
- Sponsor type
- US federal agency
- Collaborators
- Bausch Health Americas, Inc.
- Responsible party
- Sponsor-investigator, David E. Kaplan, MD MSc, Corporal Michael J. Crescenz VA Medical Center
- Investigators
- David E Kaplan, MD, MSc, Principal investigator, Corporal Michael J. Crescenz VA Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01951209
- Sponsor's protocol ID
- 01478
- Status last verified
- Mar 2021
- First submitted
- 20 Sep 2013
- Last updated
- 11 Mar 2021
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- Yes: Deidentified primary data will be made available for verification
Publications
Doi H, Iyer TK, Carpenter E, Li H, Chang KM, Vonderheide RH, Kaplan DE. Dysfunctional B-cell activation in cirrhosis resulting from hepatitis C infection associated with disappearance of CD27-positive B-cell population. Hepatology. 2012 Mar;55(3):709-19. doi: 10.1002/hep.24689. Epub 2012 Jan 19.
PubMed 21932384
Study at a glance
From the registry record, last updated by the sponsor on 11 Mar 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Prospective Pilot Study of the Effect of Rifaximin on B-Cell Dysregulation in Cirrhosis Due to Chronic Hepatitis C Infection
- ClinicalTrials.gov ID
- NCT01951209
- Acronym / sponsor ID
- 01478
- Conditions
- Liver Cirrhosis, Chronic Hepatitis C
- Keywords
- Human, Hepatitis C, Cirrhosis, B-cell, Rifaximin
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Inadequate enrollment prior to expiration date of unreplaceable blinded investigational product
- Enrolment
- 13 participants (actual)
- Lead sponsor
- David E. Kaplan, MD MScUS federal agency
- Collaborators
- Bausch Health Americas, Inc.
- Study start
- 17 Nov 2016 (actual)
- Primary completion
- 17 Nov 2016 (actual)
- Study completion
- 12 Jun 2017 (actual)
- First posted
- 26 Sep 2013 (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.
Hepatitis C is the leading cause of chronic liver disease and cirrhosis in United States veterans. Cirrhosis is associated with impaired antibody responses and increased risk of bacterial infections. We have recently identified that cirrhosis is associated with abnormalities of memory B-cells, cells that make antibodies and help protect against bacterial infections. We have identified that chemicals associated with gut bacteria might play a role in causing these B-cell abnormalities. It is well known that gut bacteria have increased access to the blood in individuals with cirrhosis, a process called bacterial translocation. We hypothesize that reducing bacteria counts in the gut by using poorly-absorbed antibiotics (also known as selective gut decontamination) will partially reverse losses of memory B-cells in cirrhosis by reducing bacterial translocation.
Detailed description
We intend to enroll 18 patients with cirrhosis who do not have hepatic encephalopathy to prospectively evaluate the impact of rifaximin on B-cell phenotype and function. We plan to employ a randomized, double-masked, prospective crossover design to minimize bias. Subjects will be randomized to receive either rifaximin SSD 80mg or a matched placebo once daily for 12 weeks then crossed over to opposite therapy for 12 weeks. Serum and lymphocytes will be collected at baseline and every 4 weeks for in vitro assessment markers of gut microbial translocation and B-cell assays. Stool will be collected at baseline and every 12 weeks for future evaluation of changes of the gut microbiome.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Rifaximin/Placebo | Experimental | Drug: Rifaximin, Drug: PlaceboRifaximin 550mg po bid for 12 weeks followed by crossover to matched placebo po bid x 12 weeks |
| Placebo/Rifaximin SSD | Experimental | Drug: Rifaximin, Drug: PlaceboMatched placebo po bid for 12 weeks followed by crossover to Rifaximin 550mg po bid x 12 weeks |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Current or prior chronic Hepatitis C infection as documented by detectable HCV RNA in prior 5 years
- Child-Turcotte-Pugh stage A5-B8. Cirrhosis diagnosis may be based on either histological criteria (an previous liver biopsy showing F4/4 or F5-6/6 fibrosis) or clinical criteria (nodular liver on abdominal imaging, splenomegaly, thrombocytopenia, spider telangiectasias, palmar erythema, ascites, varices).
- Platelet count < 175,000/ul
- Subject capable of giving informed consent
Key exclusion criteria (17 listed)
- Active alcohol use > 20g/d
- Current or planned (within following 6 months) antiviral therapy for hepatitis C
- HIV co-infection
- Diagnosis of overt hepatic encephalopathy
- Current lactulose use
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 |
|---|---|---|
| RifaximinAlso: Rifaximin (Xifaxan)550mg orally twice daily for 12 weeks | Drug | Placebo/Rifaximin SSD, Rifaximin/Placebo |
| PlaceboMatched placebo | Drug | Placebo/Rifaximin SSD, Rifaximin/Placebo |
Primary outcome
Change in CD27+ B-cell frequency
Time frame: Week 0 (Baseline) to Week 12
1 secondary outcome
Change in basal B-cell activation
Time frame: Week 0 to Week 12
Results and safety
The study was stopped early (reason given: Inadequate enrollment prior to expiration date of unreplaceable blinded investigational product). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Mar 2021.
- Background: PubMed 21932384Doi H, Iyer TK, Carpenter E, Li H, Chang KM, Vonderheide RH, Kaplan DE. Dysfunctional B-cell activation in cirrhosis resulting from hepatitis C infection associated with disappearance of CD27-positive B-cell population. Hepatology. 2012 Mar;55(3):709-19. doi: 10.1002/hep.24689. Epub 2012 Jan 19.
- Individual participant dataSharing planned: Yes. Deidentified primary data will be made available for verification
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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.
David E Kaplan, MD, MSc principal investigator
Corporal Michael J. Crescenz VA Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Rifaximin in people with Liver Cirrhosis and Chronic Hepatitis C, run by David E. Kaplan, MD MSc 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 4 inclusion and 17 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 11 Mar 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?
The study was stopped early (reason given: Inadequate enrollment prior to expiration date of unreplaceable blinded investigational product). 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?
Change in CD27+ B-cell frequency (time frame: Week 0 (Baseline) to Week 12). 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 NCT01951209, 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 11 Mar 2021.