Chronic Hepatitis C InfectionNCT01711164
The Role of FGL2-FcgammaRIIB Inhibitory Pathway in Human Viral Hepatitis
An observational study of Chronic Hepatitis C Infection, run by University Health Network, Toronto at 1 site in Canada.
Trial summary
Viral hepatitis is a serious world health problem affecting over 1 billion people worldwide. Presently the lack of highly effective treatments results in many patients requiring liver transplantation or death. Read more about this study
- Who is it for?
- Ages 18 to 70 yearsHealthy volunteers can take part
- Conditions the study is for
- Chronic Hepatitis C Infection
- How many people
- 106 participants
- Where
- 1 siteCanada
- Study dates
- Jan 2014to Sep 2016
- 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 to 70 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Study population: Patients being followed by hepatologists and considering treatment of Hepatitis C vs controls derived from potential live liver donors (for transplant)
Who may be able to join
- Able and willing to give written informed consent
- Willing to follow the study protocol
- Between >18 and <70 years of age, both gender
- No history of active alcohol or drug abuse
- Adequate contraception for both gender
- Diagnosis of chronic HCV infection based on two positive serology tests.
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- Pre- and post treatment viral load data must be available
- Naïve to antiviral treatment
- A pre treatment liver biopsy should be available for all patients
Who cannot join
- All other genotypes than genotype 1
- Less than 18 or greater than 70 years of age
- Pregnancy
- Co-infection with HBV (hepatitis B virus), HDV (Hepatitis Delta virus) or HIV co-infection
- Coexistence of liver disease of other etiology (autoimmune, alcohol)
- Evidence of hepatocellular carcinoma
Trial locations and contacts
1 site in 1 country.
About this study
Viral hepatitis is a serious world health problem affecting over 1 billion people worldwide. Presently the lack of highly effective treatments results in many patients requiring liver transplantation or death. The investigators have defined the role of a unique molecule FGL2 and its receptor fc-gammaR and its role in the pathogenesis of both experimental and human hepatitis. The studies proposed in the present proposal will test the hypothesis that measuring levels of fgl2 in plasma will identify individuals that will go on to develop chronic disease and inhibition of binding of fgl2 to its receptor will allow the host with both acute and chronic disease to develop an appropriate immune response and clear the virus. The studies will provide rationale for generation of new therapies to improve the treatment of patients with acute and chronic viral hepatitis by targeting fgl2.
Read the detailed description
Hepatitis C Virus (HCV) infection affects more than 200 million individuals worldwide. Only a fraction of infected individuals clear the virus, whereas the majority (70%) develops chronic infection. The current standard of care, pegylated interferon/ ribavirin (pegIFN/rib) is effective in only 50% of patients. Patients who fail anti-viral therapy gradually progress to end-stage liver disease and hepatocellular cancer; which can only be cured by a liver transplant. The reasons for treatment failure are unclear but involve both viral and host factors. One significant factor may be impaired T cell function. Chronic HCV infection is associated with functionally impaired or exhausted cytotoxic T lymphocytes (CTLs), with decreased anti-viral cytokine production, cytotoxicity and proliferative capacity. The investigators recently showed that many patients who fail treatment have elevated frequencies of CD4+CD25+Foxp3+regulatory T cells (Tregs) producing the novel fibrinogen-like-protein 2 (FGL2/fibroleukin) which appears to impair HCV specific immune responses. Binding of FGL2 to the FcγRIIB receptor leads to inhibition of dendritic cell (DC) maturation, B cell apoptosis and inhibition of development of effective CD4+and CD8+T and B cell anti-viral responses. In HCV, increased levels of secreted FGL2 may suppress anti-viral immune responses and promote disease progression.
Hypothesis: HCV suppresses innate and adaptive anti-viral immune responses through the FGL2-FcγRIIB inhibitory pathway. Inhibition of this pathway will restore effective virus-specific immunity and lead to successful viral eradication.
Significance: These studies will establish the importance of FGL2-FcγRIIB inhibitory pathway in the pathogenesis of HCV chronic infection and provide a novel therapeutic approach to improve virus eradication and long term patient outcomes.
- Conditions
- Chronic Hepatitis C Infection
- Keywords
- HCV, T regulatory cells (Tregs), FGL2
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 |
|---|---|---|
| patients | Chronic HCV patients who undergo antiviral therapy | |
| Healthy controls | healthy controls who are willing to give blood and liver tissue samples |
What is being measured
The primary outcome is the main question the study is designed to answer.
To correlate plasma levels of FGL2 in patients who undergo antiviral therapy for chronic HCV infection with clinical outcome
Measured: 6 months after end of antiviral treatment
Secondary outcomes (1)
to correlate levels of FGL2 to numbers and immune function of CD4+ and CD8+ T cells, and DC activity
Measured: at all timepoints; pre-treatment, at wks 4, 12 and 48 of treatment and 6 months after end of treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Oct 2012 (estimated)
- Study startJan 2014
- Primary completionMay 2016
- Study completionSep 2016
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 Chronic Hepatitis C InfectionStudies of the same condition, open and under way.
- More trials run by University Health Network, TorontoThe 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-control
- Time perspective
- Prospective
- Enrolment
- 106 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Health Network, Toronto
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Nazia Selzner, MD PhD, Principal investigator, University Health Network, Toronto
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01711164
- Sponsor's protocol ID
- 12-5129-BE
- Status last verified
- Nov 2016
- First submitted
- 12 Oct 2012
- Last updated
- 29 Nov 2016
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Foerster K, Helmy A, Zhu Y, Khattar R, Adeyi OA, Wong KM, Shalev I, Clark DA, Wong PY, Heathcote EJ, Phillips MJ, Grant DR, Renner EL, Levy GA, Selzner N. The novel immunoregulatory molecule FGL2: a potential biomarker for severity of chronic hepatitis C virus infection. J Hepatol. 2010 Oct;53(4):608-15. doi: 10.1016/j.jhep.2010.04.020. Epub 2010 Jun 17.
PubMed 20615566
Study at a glance
From the registry record, last updated by the sponsor on 29 Nov 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Role of FGL2-FcgammaRIIB Inhibitory Pathway in Human Viral Hepatitis
- ClinicalTrials.gov ID
- NCT01711164
- Acronym / sponsor ID
- 12-5129-BE
- Conditions
- Chronic Hepatitis C Infection
- Keywords
- HCV, T regulatory cells (Tregs), FGL2
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 106 participants (actual)
- Lead sponsor
- University Health Network, TorontoUniversity, hospital or other
- Study start
- Jan 2014
- Primary completion
- May 2016 (actual)
- Study completion
- Sep 2016 (actual)
- First posted
- 22 Oct 2012 (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.
Viral hepatitis is a serious world health problem affecting over 1 billion people worldwide. Presently the lack of highly effective treatments results in many patients requiring liver transplantation or death. The investigators have defined the role of a unique molecule FGL2 and its receptor fc-gammaR and its role in the pathogenesis of both experimental and human hepatitis. The studies proposed in the present proposal will test the hypothesis that measuring levels of fgl2 in plasma will identify individuals that will go on to develop chronic disease and inhibition of binding of fgl2 to its receptor will allow the host with both acute and chronic disease to develop an appropriate immune response and clear the virus. The studies will provide rationale for generation of new therapies to improve the treatment of patients with acute and chronic viral hepatitis by targeting fgl2.
Detailed description
Hepatitis C Virus (HCV) infection affects more than 200 million individuals worldwide. Only a fraction of infected individuals clear the virus, whereas the majority (70%) develops chronic infection. The current standard of care, pegylated interferon/ ribavirin (pegIFN/rib) is effective in only 50% of patients. Patients who fail anti-viral therapy gradually progress to end-stage liver disease and hepatocellular cancer; which can only be cured by a liver transplant. The reasons for treatment failure are unclear but involve both viral and host factors. One significant factor may be impaired T cell function. Chronic HCV infection is associated with functionally impaired or exhausted cytotoxic T lymphocytes (CTLs), with decreased anti-viral cytokine production, cytotoxicity and proliferative capacity. The investigators recently showed that many patients who fail treatment have elevated frequencies of CD4+CD25+Foxp3+regulatory T cells (Tregs) producing the novel fibrinogen-like-protein 2 (FGL2/fibroleukin) which appears to impair HCV specific immune responses. Binding of FGL2 to the FcγRIIB receptor leads to inhibition of dendritic cell (DC) maturation, B cell apoptosis and inhibition of development of effective CD4+and CD8+T and B cell anti-viral responses. In HCV, increased levels of secreted FGL2 may suppress anti-viral immune responses and promote disease progression.
Hypothesis: HCV suppresses innate and adaptive anti-viral immune responses through the FGL2-FcγRIIB inhibitory pathway. Inhibition of this pathway will restore effective virus-specific immunity and lead to successful viral eradication.
Significance: These studies will establish the importance of FGL2-FcγRIIB inhibitory pathway in the pathogenesis of HCV chronic infection and provide a novel therapeutic approach to improve virus eradication and long term patient outcomes.
Study design
- Observational model
- Case-control
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| patients | – | –Chronic HCV patients who undergo antiviral therapy |
| Healthy controls | – | –healthy controls who are willing to give blood and liver tissue samples |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- Patients being followed by hepatologists and considering treatment of Hepatitis C vs controls derived from potential live liver donors (for transplant)
Key inclusion criteria (9 listed)
- Able and willing to give written informed consent
- Willing to follow the study protocol
- Between >18 and <70 years of age, both gender
- No history of active alcohol or drug abuse
- Adequate contraception for both gender
Key exclusion criteria (6 listed)
- All other genotypes than genotype 1
- Less than 18 or greater than 70 years of age
- Pregnancy
- Co-infection with HBV (hepatitis B virus), HDV (Hepatitis Delta virus) or HIV co-infection
- Coexistence of liver disease of other etiology (autoimmune, alcohol)
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
To correlate plasma levels of FGL2 in patients who undergo antiviral therapy for chronic HCV infection with clinical outcome
Time frame: 6 months after end of antiviral treatment
1 secondary outcome
to correlate levels of FGL2 to numbers and immune function of CD4+ and CD8+ T cells, and DC activity
Time frame: at all timepoints; pre-treatment, at wks 4, 12 and 48 of treatment and 6 months after end of 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 Nov 2016.
- Results publication: PubMed 20615566Foerster K, Helmy A, Zhu Y, Khattar R, Adeyi OA, Wong KM, Shalev I, Clark DA, Wong PY, Heathcote EJ, Phillips MJ, Grant DR, Renner EL, Levy GA, Selzner N. The novel immunoregulatory molecule FGL2: a potential biomarker for severity of chronic hepatitis C virus infection. J Hepatol. 2010 Oct;53(4):608-15. doi: 10.1016/j.jhep.2010.04.020. Epub 2010 Jun 17.
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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.
Nazia Selzner, MD PhD principal investigator
University Health Network, Toronto
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 Chronic Hepatitis C Infection, run by University Health Network, Toronto at 1 site in Canada.
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 9 inclusion and 6 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 Nov 2016. 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 Canada. 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?
To correlate plasma levels of FGL2 in patients who undergo antiviral therapy for chronic HCV infection with clinical outcome (time frame: 6 months after end of antiviral 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 NCT01711164, 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 Nov 2016.