Hepatitis CNCT03186235
T Regulatory Cells in Hepatitis c Infected Patients
An observational study of Hepatitis C, run by Assiut University at 1 site in Egypt.
Trial summary
Chronic hepatitis C infection is a global worldwide health problem with an increasing burden year-by-year, particularly in areas with a high endemicity like Egypt . The World Health Organization estimates that approximately 200 million people worldwide are infected with hepatitis c virus. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Hepatitis C
- What is being tested?
- Flow cytometry
- How many people
- 88 participants
- Where
- 1 siteEgypt
- Study dates
- 1 Jul 2018to 1 Aug 2019
- 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 Any age
- All sexes
- Child, Adult, Older adult
Study population: . All participants were recruited from Assiut Liver Institute for Treatment of Hepatitis C Virus and Assiut University Hospitals outpatient clinics, Assiut, Egypt. Healthy donors will be attending blood bank of Assiut University Hospital during the study period. They will be negative for known serologic markers of hepatitis (B \& C) including hepatitis B surface antigen and antibodies to Hepatitis C virus
Who may be able to join
- positive for hepatitis c viral antibodies by Enzyme Linked Immuno Sorbent Assay and by hepatitis c viral Ribo Nucleic Acid Real time Polymerase Chain Reaction
Who cannot join
- are pregnancy, history of Schistosoma infection, inflammatory bowel diseases or suspected inflammatory bowel diseases , autoimmune diseases including rheumatoid arthritis, and any patients on systemic immunomodulators
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Regulatory T Cells and Their Cytokines Profile in Different Groups of Hepatitis c Infected Patients: A Case Control Study
Chronic hepatitis C infection is a global worldwide health problem with an increasing burden year-by-year, particularly in areas with a high endemicity like Egypt . The World Health Organization estimates that approximately 200 million people worldwide are infected with hepatitis c virus. In Egypt, it was estimated that 15 % of Egyptians have serologic evidence of hepatitis C viral infection .
Read the detailed description
The ultimate outcome of hepatitis c viral infection is determined by the host immune response. Patients with acute hepatitis c viral infection who did not clear the virus developed chronicity. Persistant hepatitis c virus -specific cytotoxic T-cell responses in the liver have been associated with the development of hepatic inflammation which may ultimately lead to liver cirrhosis. One of the potential mechanisms that might modulate hepatitis c virus -specific immune responses is the inhibitory role of the regulatory T cells.
Regulatory T cells are a subtype of T-cells that play a fundamental role in maintaining immune homeostasis to balance between the tissue-damaging and protective effects of the immune response. Regulatory T cells are characterized by the expression of the Forkhead box protein P3 transcription factor in the nucleus and is generally accepted as the single best marker for regulatory Tcells. In cases of hepatitis c virus infection, the role of regulatory Tcells is still controversial and most of studies yielded conflicting reports. This conflict may be explained by the heterogeneity in the methods and sites of studying the frequency of regulatory T cells.
There are strong evidences that regulatory T cells and their cytokines may play an important role in the induction of tolerance in the liver.
Interleukin 35 is an immune-suppressive cytokine expressed in stimulated human regulatory Tcells during inflammatory responses and consists of Interlukin-12a ( Interleukin 12p35 subunit) and IL-27b chains, encoded by the Interleukin 12A and Epstien Bar I3 genes, respectively. It is a novel heterodimeric cytokine belonging to the Interleukin 12 family, and little is known about its receptor. Activated peripheral blood mononuclear cell (PBMC)- derived human regulatory T cells have been shown to express and secrete large amounts of Interleukin 35, which contributes significantly to the suppressive capacity of regulatory T cells in an Interlukin 35-dependent manner.
Additionally, human regulatory T cell -derived IL35 is required for the conversion of human conventional cluster of differentiation 4+Foxp3_ T cells into induced T regulatory 35 cells, which then promote the generation of more induced T regulatory 35 cells via Interleukin 35 secretion, resulting in infectious tolerance (18). In addition, Interleukin 35 has been shown to suppress the T helper (Th) cells Th1 and Th17.
In this study, investigators will evaluate the possible role of regulatory T cells and their cytokines in different groups of hepatitis c infected patients by investigating the frequency of regulatory T cells and serum level of IL35 and examining their relationship to the various patterns of hepatitis c viral persistence, hepatitis c virus pathogenesis, complications with cirrhosis and hepatocellular carcinoma in an attempt to estimate the future value of using anti IL35 and regulatory T cell depletion in those patients.
- Conditions
- Hepatitis C
- Being tested
- Flow cytometry
- Medical subject headings
- Hepatitis C
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Flow cytometryOther
Isolation of T regulatory cells from blood
| Study group | Role | What they receive |
|---|---|---|
| Group I : 18 healthy controls | Two milliliter of heparinized whole blood samples will be used for the Flow cytometry analysis to quantify percentages of circulating regulatory T cells in human peripheral blood in chronic hepatitis C patients in comparison with that of controls by four-colour flow cytometry analysis using a set of fluorochrome-labeled monoclonal antibodies against regulatory T cell surface markers and estimation of the level of IL35 by ElISA. Receives: Other: Flow cytometry | |
| group II : 16 Hepatitis C infected patients (naïve) | Two milliliter of heparinized whole blood samples will be used for the Flow cytometry analysis to quantify percentages of circulating regulatory T cells in human peripheral blood in chronic hepatitis C patients in comparison with that of controls by four-colour flow cytometry analysis using a set of fluorochrome-labeled monoclonal antibodies against regulatory T cell surface markers and estimation of the level of IL35 by ElISA. Receives: Other: Flow cytometry | |
| group III:18 HCV-infected patients complicated with cirrhosis | Two milliliter of heparinized whole blood samples will be used for the Flow cytometry analysis to quantify percentages of circulating regulatory T cells in human peripheral blood in chronic hepatitis C patients in comparison with that of controls by four-colour flow cytometry analysis using a set of fluorochrome-labeled monoclonal antibodies against regulatory T cell surface markers and estimation of the level of IL35 by ElISA. Receives: Other: Flow cytometry | |
| group IV: 18 HCV-infected patients with Hepatocellular cancer | Two milliliter of heparinized whole blood samples will be used for the Flow cytometry analysis to quantify percentages of circulating regulatory T cells in human peripheral blood in chronic hepatitis C patients in comparison with that of controls by four-colour flow cytometry analysis using a set of fluorochrome-labeled monoclonal antibodies against regulatory T cell surface markers and estimation of the level of IL35 by ElISA. Receives: Other: Flow cytometry | |
| Group V:18 patients with sustained viral response (SVR). | Two milliliter of heparinized whole blood samples will be used for the Flow cytometry analysis to quantify percentages of circulating regulatory T cells in human peripheral blood in chronic hepatitis C patients in comparison with that of controls by four-colour flow cytometry analysis using a set of fluorochrome-labeled monoclonal antibodies against regulatory T cell surface markers and estimation of the level of IL35 by ElISA. Receives: Other: Flow cytometry |
What is being measured
The primary outcome is the main question the study is designed to answer.
frequency of T regulatory cells in all 6 groups using flow cytometry
frequency of T regulatory cells will be estimated by flow cytometry in all 6 groups
Measured: An average 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Jun 2017
- Study start1 Jul 2018
- Primary completion1 Aug 2019
- Study completion1 Aug 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (8)Papers the sponsor has linked to this study.
- Other trials for Hepatitis CStudies of the same condition, open and under way.
- More trials run by Assiut UniversityThe 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
- Other
- Time perspective
- Other
- Enrolment
- 88 participants (actual)
Sponsor and investigators
- Lead sponsor
- Assiut University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Esraa Hassan,MD, Assiut University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03186235
- Sponsor's protocol ID
- Esraa
- Status last verified
- Dec 2019
- First submitted
- 10 Jun 2017
- Last updated
- 18 Dec 2019
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Lauer GM, Walker BD. Hepatitis C virus infection. N Engl J Med. 2001 Jul 5;345(1):41-52. doi: 10.1056/NEJM200107053450107. No abstract available.
PubMed 11439948Klenerman P, Thimme R. T cell responses in hepatitis C: the good, the bad and the unconventional. Gut. 2012 Aug;61(8):1226-34. doi: 10.1136/gutjnl-2011-300620. Epub 2011 Aug 28.
PubMed 21873736Bowen DG, Walker CM. Adaptive immune responses in acute and chronic hepatitis C virus infection. Nature. 2005 Aug 18;436(7053):946-52. doi: 10.1038/nature04079.
PubMed 16107834Hartling HJ, Gaardbo JC, Ronit A, Knudsen LS, Ullum H, Vainer B, Clausen MR, Skogstrand K, Gerstoft J, Nielsen SD. CD4(+) and CD8(+) regulatory T cells (Tregs) are elevated and display an active phenotype in patients with chronic HCV mono-infection and HIV/HCV co-infection. Scand J Immunol. 2012 Sep;76(3):294-305. doi: 10.1111/j.1365-3083.2012.02725.x.
PubMed 22671952Sturm N, Thelu MA, Camous X, Dimitrov G, Ramzan M, Dufeu-Duchesne T, Bonorino P, Guillermet C, Brambilla E, Arvers P, Pernollet M, Leroy V, Zarski JP, Marche PN, Jouvin-Marche E. Characterization and role of intra-hepatic regulatory T cells in chronic hepatitis C pathogenesis. J Hepatol. 2010 Jul;53(1):25-35. doi: 10.1016/j.jhep.2010.02.024. Epub 2010 Apr 20.
PubMed 20452085Sakaguchi S, Yamaguchi T, Nomura T, Ono M. Regulatory T cells and immune tolerance. Cell. 2008 May 30;133(5):775-87. doi: 10.1016/j.cell.2008.05.009.
PubMed 18510923Magg T, Mannert J, Ellwart JW, Schmid I, Albert MH. Subcellular localization of FOXP3 in human regulatory and nonregulatory T cells. Eur J Immunol. 2012 Jun;42(6):1627-38. doi: 10.1002/eji.201141838.
PubMed 22678915Adams DH, Eksteen B, Curbishley SM. Immunology of the gut and liver: a love/hate relationship. Gut. 2008 Jun;57(6):838-48. doi: 10.1136/gut.2007.122168. Epub 2008 Jan 18. No abstract available.
PubMed 18203807
Study at a glance
From the registry record, last updated by the sponsor on 18 Dec 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Regulatory T Cells and Their Cytokines Profile in Different Groups of Hepatitis c Infected Patients: A Case Control Study
- ClinicalTrials.gov ID
- NCT03186235
- Acronym / sponsor ID
- Esraa
- Conditions
- Hepatitis C
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 88 participants (actual)
- Lead sponsor
- Assiut UniversityUniversity, hospital or other
- Study start
- 1 Jul 2018 (actual)
- Primary completion
- 1 Aug 2019 (actual)
- Study completion
- 1 Aug 2019 (actual)
- First posted
- 14 Jun 2017 (actual)
- 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.
Chronic hepatitis C infection is a global worldwide health problem with an increasing burden year-by-year, particularly in areas with a high endemicity like Egypt . The World Health Organization estimates that approximately 200 million people worldwide are infected with hepatitis c virus. In Egypt, it was estimated that 15 % of Egyptians have serologic evidence of hepatitis C viral infection .
Detailed description
The ultimate outcome of hepatitis c viral infection is determined by the host immune response. Patients with acute hepatitis c viral infection who did not clear the virus developed chronicity. Persistant hepatitis c virus -specific cytotoxic T-cell responses in the liver have been associated with the development of hepatic inflammation which may ultimately lead to liver cirrhosis. One of the potential mechanisms that might modulate hepatitis c virus -specific immune responses is the inhibitory role of the regulatory T cells.
Regulatory T cells are a subtype of T-cells that play a fundamental role in maintaining immune homeostasis to balance between the tissue-damaging and protective effects of the immune response. Regulatory T cells are characterized by the expression of the Forkhead box protein P3 transcription factor in the nucleus and is generally accepted as the single best marker for regulatory Tcells. In cases of hepatitis c virus infection, the role of regulatory Tcells is still controversial and most of studies yielded conflicting reports. This conflict may be explained by the heterogeneity in the methods and sites of studying the frequency of regulatory T cells.
There are strong evidences that regulatory T cells and their cytokines may play an important role in the induction of tolerance in the liver.
Interleukin 35 is an immune-suppressive cytokine expressed in stimulated human regulatory Tcells during inflammatory responses and consists of Interlukin-12a ( Interleukin 12p35 subunit) and IL-27b chains, encoded by the Interleukin 12A and Epstien Bar I3 genes, respectively. It is a novel heterodimeric cytokine belonging to the Interleukin 12 family, and little is known about its receptor. Activated peripheral blood mononuclear cell (PBMC)- derived human regulatory T cells have been shown to express and secrete large amounts of Interleukin 35, which contributes significantly to the suppressive capacity of regulatory T cells in an Interlukin 35-dependent manner.
Additionally, human regulatory T cell -derived IL35 is required for the conversion of human conventional cluster of differentiation 4+Foxp3_ T cells into induced T regulatory 35 cells, which then promote the generation of more induced T regulatory 35 cells via Interleukin 35 secretion, resulting in infectious tolerance (18). In addition, Interleukin 35 has been shown to suppress the T helper (Th) cells Th1 and Th17.
In this study, investigators will evaluate the possible role of regulatory T cells and their cytokines in different groups of hepatitis c infected patients by investigating the frequency of regulatory T cells and serum level of IL35 and examining their relationship to the various patterns of hepatitis c viral persistence, hepatitis c virus pathogenesis, complications with cirrhosis and hepatocellular carcinoma in an attempt to estimate the future value of using anti IL35 and regulatory T cell depletion in those patients.
Study design
- Observational model
- Other
- Time perspective
- Other
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| Group I : 18 healthy controls | – | Other: Flow cytometryTwo milliliter of heparinized whole blood samples will be used for the Flow cytometry analysis to quantify percentages of circulating regulatory T cells in human peripheral blood in chronic hepatitis C patients in comparison with that of controls by four-colour flow cytometry analysis using a set of fluorochrome-labeled monoclonal antibodies against regulatory T cell surface markers and estimation of the level of IL35 by ElISA. |
| group II : 16 Hepatitis C infected patients (naïve) | – | Other: Flow cytometryTwo milliliter of heparinized whole blood samples will be used for the Flow cytometry analysis to quantify percentages of circulating regulatory T cells in human peripheral blood in chronic hepatitis C patients in comparison with that of controls by four-colour flow cytometry analysis using a set of fluorochrome-labeled monoclonal antibodies against regulatory T cell surface markers and estimation of the level of IL35 by ElISA. |
| group III:18 HCV-infected patients complicated with cirrhosis | – | Other: Flow cytometryTwo milliliter of heparinized whole blood samples will be used for the Flow cytometry analysis to quantify percentages of circulating regulatory T cells in human peripheral blood in chronic hepatitis C patients in comparison with that of controls by four-colour flow cytometry analysis using a set of fluorochrome-labeled monoclonal antibodies against regulatory T cell surface markers and estimation of the level of IL35 by ElISA. |
| group IV: 18 HCV-infected patients with Hepatocellular cancer | – | Other: Flow cytometryTwo milliliter of heparinized whole blood samples will be used for the Flow cytometry analysis to quantify percentages of circulating regulatory T cells in human peripheral blood in chronic hepatitis C patients in comparison with that of controls by four-colour flow cytometry analysis using a set of fluorochrome-labeled monoclonal antibodies against regulatory T cell surface markers and estimation of the level of IL35 by ElISA. |
| Group V:18 patients with sustained viral response (SVR). | – | Other: Flow cytometryTwo milliliter of heparinized whole blood samples will be used for the Flow cytometry analysis to quantify percentages of circulating regulatory T cells in human peripheral blood in chronic hepatitis C patients in comparison with that of controls by four-colour flow cytometry analysis using a set of fluorochrome-labeled monoclonal antibodies against regulatory T cell surface markers and estimation of the level of IL35 by ElISA. |
Who may qualify
- Sex
- All
- Age groups
- Child, Adult, Older adult
- Study population
- . All participants were recruited from Assiut Liver Institute for Treatment of Hepatitis C Virus and Assiut University Hospitals outpatient clinics, Assiut, Egypt. Healthy donors will be attending blood bank of Assiut University Hospital during the study period. They will be negative for known serologic markers of hepatitis (B \& C) including hepatitis B surface antigen and antibodies to Hepatitis C virus
Key inclusion criteria (1 listed)
- positive for hepatitis c viral antibodies by Enzyme Linked Immuno Sorbent Assay and by hepatitis c viral Ribo Nucleic Acid Real time Polymerase Chain Reaction
Key exclusion criteria (1 listed)
- are pregnancy, history of Schistosoma infection, inflammatory bowel diseases or suspected inflammatory bowel diseases , autoimmune diseases including rheumatoid arthritis, and any patients on systemic immunomodulators
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 |
|---|---|---|
| Flow cytometryIsolation of T regulatory cells from blood | Other | Group I : 18 healthy controls, Group V:18 patients with sustained viral response (SVR)., group II : 16 Hepatitis C infected patients (naïve), group III:18 HCV-infected patients complicated with cirrhosis, group IV: 18 HCV-infected patients with Hepatocellular cancer |
Primary outcome
frequency of T regulatory cells in all 6 groups using flow cytometry
Time frame: An average 1 year
frequency of T regulatory cells will be estimated by flow cytometry in all 6 groups
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 18 Dec 2019.
- Background: PubMed 11439948Lauer GM, Walker BD. Hepatitis C virus infection. N Engl J Med. 2001 Jul 5;345(1):41-52. doi: 10.1056/NEJM200107053450107. No abstract available.
- Background: PubMed 21873736Klenerman P, Thimme R. T cell responses in hepatitis C: the good, the bad and the unconventional. Gut. 2012 Aug;61(8):1226-34. doi: 10.1136/gutjnl-2011-300620. Epub 2011 Aug 28.
- Background: PubMed 16107834Bowen DG, Walker CM. Adaptive immune responses in acute and chronic hepatitis C virus infection. Nature. 2005 Aug 18;436(7053):946-52. doi: 10.1038/nature04079.
- Background: PubMed 22671952Hartling HJ, Gaardbo JC, Ronit A, Knudsen LS, Ullum H, Vainer B, Clausen MR, Skogstrand K, Gerstoft J, Nielsen SD. CD4(+) and CD8(+) regulatory T cells (Tregs) are elevated and display an active phenotype in patients with chronic HCV mono-infection and HIV/HCV co-infection. Scand J Immunol. 2012 Sep;76(3):294-305. doi: 10.1111/j.1365-3083.2012.02725.x.
- Background: PubMed 20452085Sturm N, Thelu MA, Camous X, Dimitrov G, Ramzan M, Dufeu-Duchesne T, Bonorino P, Guillermet C, Brambilla E, Arvers P, Pernollet M, Leroy V, Zarski JP, Marche PN, Jouvin-Marche E. Characterization and role of intra-hepatic regulatory T cells in chronic hepatitis C pathogenesis. J Hepatol. 2010 Jul;53(1):25-35. doi: 10.1016/j.jhep.2010.02.024. Epub 2010 Apr 20.
- Background: PubMed 18510923Sakaguchi S, Yamaguchi T, Nomura T, Ono M. Regulatory T cells and immune tolerance. Cell. 2008 May 30;133(5):775-87. doi: 10.1016/j.cell.2008.05.009.
- Background: PubMed 22678915Magg T, Mannert J, Ellwart JW, Schmid I, Albert MH. Subcellular localization of FOXP3 in human regulatory and nonregulatory T cells. Eur J Immunol. 2012 Jun;42(6):1627-38. doi: 10.1002/eji.201141838.
- Background: PubMed 18203807Adams DH, Eksteen B, Curbishley SM. Immunology of the gut and liver: a love/hate relationship. Gut. 2008 Jun;57(6):838-48. doi: 10.1136/gut.2007.122168. Epub 2008 Jan 18. No abstract available.
- Individual participant dataSharing planned: No
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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.
The record lists no contact. Use the official record to reach the sponsor.
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 Hepatitis C, run by Assiut University at 1 site in Egypt.
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 1 inclusion and 1 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 18 Dec 2019. 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 Egypt. 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?
frequency of T regulatory cells in all 6 groups using flow cytometry (time frame: An average 1 year). 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 NCT03186235, which also lists 8 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 18 Dec 2019.