Haemodialysis ComplicationNCT02981992
T Regulatory Cells in Hemodialysis Patients: Observational Study
An observational study of Haemodialysis Complication and Immune Dysfunction, run by Fondazione IRCCS Policlinico San Matteo di Pavia at 1 site in Italy.
Trial summary
In this observational study, the investigators evaluated the Treg number and function in a population of patients undergoing hemodialysis (HD). In particular, the investigators considered the relationship of Treg cell status with the different HD modalities and clinical parameters. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Haemodialysis Complication, Immune Dysfunction
- How many people
- 30 participants
- Where
- 1 siteItaly
- Study dates
- Feb 2011to Feb 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 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: A total number of 30 prevalent patients undergoing chronic renal replacement terapy with hemodialysis (HD) has been included in the evaluation. The study duration was 12 months, with a check of the number and function of Treg every 3 months. During the study patients were subjected to dialysis and farmacology treatment as usual, without any alteration linked specifically to this protocol. The number and function of Treg were measured as a percentage of CD4+CD25bright+pre-dialysis in the last week of each third month of the study.
Who may be able to join
- Patients with spKt/V ≥ 1,2
Who cannot join
- Cancer
- Pregnant or breastfeeding
- Sepsis
- Kidney or other organ transplant
- Major cardiovascular events in the previous 3 months
- Patients unable to understand or interdicted
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Observational Study on T Regulatory Cells in Hemodialysis Patients
In this observational study, the investigators evaluated the Treg number and function in a population of patients undergoing hemodialysis (HD).
In particular, the investigators considered the relationship of Treg cell status with the different HD modalities and clinical parameters.
Read the detailed description
Patients on hemodialysis (HD) present an elevated risk of cardiovascular disease, cancer and infectious events that may lead to the high morbidity and mortality rate characteristic of this population. Many causes can explain this increased risk, including inflammation that, in turn, might be secondary to dialysis-specific factors, such as contaminated water, dialysis modality and dialysis membranes used for treatment.
In addition to chronic inflammatory, in HD patients is also present a significant alteration of the immune system resulting in chronic lymphocytic infiltration, alteration of T-helper balance (Th1/Th2) etc. The immune response is controlled by very complex mechanisms; it is mediated by interaction between antigen-presenting cells (APC), CD4+ T helper (Th) and T cells CD4+ CD25+ regulatory (Treg), a cell subpopulation of T CD4+ expressing the IL-2 receptor (CD25) and forkhead factor (foxp 3). Treg cells contribute to the maintenance of peripheral tolerance by suppressing the immune response to self-normal or tumor antigens. Treg cells control population's expansion of peripheral cells and suppress the proliferation of Th activated cells. Accessory molecules such as CTLA-4 receptors, CD28 and IL-2 cytokines and IL-6, contribute to the activation and proliferation of Treg cells.
The characterization by flow cytometry of Treg suffered for a lack of specific surface markers. These cells are generally identified on the basis of contemporary expression of molecules CD4 and CD25, but the specificity of these markers is limited, given that the CD25 is also expressed on activated lymphocytes. Recently it has been showed that the expression of Foxp3 gene is a phenomenon strictly linked to the development of regulatory activity of Treg, and so, the extent of the expression of this gene by Real Time PCR is currently considered the most specific Treg marker. There is very poor data on Treg cells function in HD. A recent study shows that in patients on chronic HD, the number of Treg is lower if compared to healthy subjects. Moreover, the Treg cells of patients on HD would present a significant impairment of their function, assessed as the ability to inhibit lymphocyte proliferation.
Those results, however, are affected by the lack of data on the characteristics of the studied patients and the type of dialysis treatment applied. In contrast, a recent study by our group showed that patients on hemodialysis with poor biocompatible membranes have a greater number of circulating Treg compared with healthy controls matched for age and sex.
Given the absence of other data, it still remains to investigate the actual significance and function of Treg in HD, considering that Treg status might potentially affect the immune response.
Therefore, the purpose of this study was to evaluate the structure and function of Treg cells in patients undergoing HD, also considering their relationship with the different HD modalities and clinical parameters.
- Conditions
- Haemodialysis Complication, Immune Dysfunction
- Medical subject headings
- Immune System Diseases
What is being measured
The primary outcome is the main question the study is designed to answer.
Treg number
Assessment of the number of Treg by flow cytometry.
Measured: Assessment of Treg number at basal control and then every 3 months for a total study period of 12 months
Secondary outcomes (2)
Treg function
Evaluation of Treg function by measuring the ability to inhibit cell proliferation in the context of a mixed lymphocyte reaction.
Measured: Assessment of Treg function at basal control and then every 3 months for a total study period of 12 months
Effect of dialysis modality
Evaluation of the number and function of Treg cells before and after dialysis (by flow cytometry and in vitro experiments), as a function of the type of dialysis treatment by use of multivariate regression models
Measured: Analysis of the number and function of Treg cells in function of the type of dialysis treatment at basal control and then every 6 months for a total study period of 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Dec 2016 (estimated)
- Study startFeb 2011
- Primary completionFeb 2014
- Study completionFeb 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for Haemodialysis ComplicationStudies of the same condition, open and under way.
- More trials run by Fondazione IRCCS Policlinico San Matteo di PaviaThe 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
- Cohort
- Time perspective
- Prospective
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Lead sponsor
- Fondazione IRCCS Policlinico San Matteo di Pavia
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Carmelo Libetta, Fondazione IRCCS Policlinico San Matteo di Pavia
- Investigators
- Carmelo Libetta, Prof, Principal investigator, Fondazione Policlinico "San Matteo", Pavia- Italy
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02981992
- Sponsor's protocol ID
- 20100014090
- Status last verified
- Nov 2016
- First submitted
- 26 Nov 2016
- Last updated
- 5 Dec 2016
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No
Publications
Hendrikx TK, van Gurp EA, Mol WM, Schoordijk W, Sewgobind VD, Ijzermans JN, Weimar W, Baan CC. End-stage renal failure and regulatory activities of CD4+CD25bright+FoxP3+ T-cells. Nephrol Dial Transplant. 2009 Jun;24(6):1969-78. doi: 10.1093/ndt/gfp005. Epub 2009 Feb 4.
PubMed 19193737Sewgobind VD, van der Laan LJ, Kho MM, Kraaijeveld R, Korevaar SS, van Dam T, Ijzermans JN, Weimar W, Baan CC. Characterization of rabbit antithymocyte globulins-induced CD25+ regulatory T cells from cells of patients with end-stage renal disease. Transplantation. 2010 Mar 27;89(6):655-66. doi: 10.1097/TP.0b013e3181c9cc7a.
PubMed 20164820Sharif MR, Chitsazian Z, Moosavian M, Raygan F, Nikoueinejad H, Sharif AR, Einollahi B. Immune disorders in hemodialysis patients. Iran J Kidney Dis. 2015 Mar;9(2):84-96.
PubMed 25851286Uda S, Mizobuchi M, Akizawa T. Biocompatible characteristics of high-performance membranes. Contrib Nephrol. 2011;173:23-29. doi: 10.1159/000328941. Epub 2011 Aug 8.
PubMed 21865772Libetta C, Esposito P, Sepe V, Portalupi V, Margiotta E, Canevari M, Dal Canton A. Dialysis treatment and regulatory T cells. Nephrol Dial Transplant. 2010 May;25(5):1723-7. doi: 10.1093/ndt/gfq055. Epub 2010 Feb 15. No abstract available.
PubMed 20157169Sepe V, Gregorini M, Rampino T, Esposito P, Coppo R, Galli F, Libetta C. Vitamin e-loaded membrane dialyzers reduce hemodialysis inflammaging. BMC Nephrol. 2019 Nov 15;20(1):412. doi: 10.1186/s12882-019-1585-6.
PubMed 31729973
Study at a glance
From the registry record, last updated by the sponsor on 5 Dec 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Observational Study on T Regulatory Cells in Hemodialysis Patients
- ClinicalTrials.gov ID
- NCT02981992
- Acronym / sponsor ID
- 20100014090
- Conditions
- Haemodialysis Complication, Immune Dysfunction
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 30 participants (actual)
- Lead sponsor
- Fondazione IRCCS Policlinico San Matteo di PaviaUniversity, hospital or other
- Study start
- Feb 2011
- Primary completion
- Feb 2014 (actual)
- Study completion
- Feb 2016 (actual)
- First posted
- 5 Dec 2016 (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.
In this observational study, the investigators evaluated the Treg number and function in a population of patients undergoing hemodialysis (HD).
In particular, the investigators considered the relationship of Treg cell status with the different HD modalities and clinical parameters.
Detailed description
Patients on hemodialysis (HD) present an elevated risk of cardiovascular disease, cancer and infectious events that may lead to the high morbidity and mortality rate characteristic of this population. Many causes can explain this increased risk, including inflammation that, in turn, might be secondary to dialysis-specific factors, such as contaminated water, dialysis modality and dialysis membranes used for treatment.
In addition to chronic inflammatory, in HD patients is also present a significant alteration of the immune system resulting in chronic lymphocytic infiltration, alteration of T-helper balance (Th1/Th2) etc. The immune response is controlled by very complex mechanisms; it is mediated by interaction between antigen-presenting cells (APC), CD4+ T helper (Th) and T cells CD4+ CD25+ regulatory (Treg), a cell subpopulation of T CD4+ expressing the IL-2 receptor (CD25) and forkhead factor (foxp 3). Treg cells contribute to the maintenance of peripheral tolerance by suppressing the immune response to self-normal or tumor antigens. Treg cells control population's expansion of peripheral cells and suppress the proliferation of Th activated cells. Accessory molecules such as CTLA-4 receptors, CD28 and IL-2 cytokines and IL-6, contribute to the activation and proliferation of Treg cells.
The characterization by flow cytometry of Treg suffered for a lack of specific surface markers. These cells are generally identified on the basis of contemporary expression of molecules CD4 and CD25, but the specificity of these markers is limited, given that the CD25 is also expressed on activated lymphocytes. Recently it has been showed that the expression of Foxp3 gene is a phenomenon strictly linked to the development of regulatory activity of Treg, and so, the extent of the expression of this gene by Real Time PCR is currently considered the most specific Treg marker. There is very poor data on Treg cells function in HD. A recent study shows that in patients on chronic HD, the number of Treg is lower if compared to healthy subjects. Moreover, the Treg cells of patients on HD would present a significant impairment of their function, assessed as the ability to inhibit lymphocyte proliferation.
Those results, however, are affected by the lack of data on the characteristics of the studied patients and the type of dialysis treatment applied. In contrast, a recent study by our group showed that patients on hemodialysis with poor biocompatible membranes have a greater number of circulating Treg compared with healthy controls matched for age and sex.
Given the absence of other data, it still remains to investigate the actual significance and function of Treg in HD, considering that Treg status might potentially affect the immune response.
Therefore, the purpose of this study was to evaluate the structure and function of Treg cells in patients undergoing HD, also considering their relationship with the different HD modalities and clinical parameters.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- A total number of 30 prevalent patients undergoing chronic renal replacement terapy with hemodialysis (HD) has been included in the evaluation. The study duration was 12 months, with a check of the number and function of Treg every 3 months. During the study patients were subjected to dialysis and farmacology treatment as usual, without any alteration linked specifically to this protocol. The number and function of Treg were measured as a percentage of CD4+CD25bright+pre-dialysis in the last week of each third month of the study.
Key inclusion criteria (1 listed)
- Patients with spKt/V ≥ 1,2
Key exclusion criteria (6 listed)
- Cancer
- Pregnant or breastfeeding
- Sepsis
- Kidney or other organ transplant
- Major cardiovascular events in the previous 3 months
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
Treg number
Time frame: Assessment of Treg number at basal control and then every 3 months for a total study period of 12 months
Assessment of the number of Treg by flow cytometry.
2 secondary outcomes
Treg function
Time frame: Assessment of Treg function at basal control and then every 3 months for a total study period of 12 months
Effect of dialysis modality
Time frame: Analysis of the number and function of Treg cells in function of the type of dialysis treatment at basal control and then every 6 months for a total study period of 12 months
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 5 Dec 2016.
- Background: PubMed 19193737Hendrikx TK, van Gurp EA, Mol WM, Schoordijk W, Sewgobind VD, Ijzermans JN, Weimar W, Baan CC. End-stage renal failure and regulatory activities of CD4+CD25bright+FoxP3+ T-cells. Nephrol Dial Transplant. 2009 Jun;24(6):1969-78. doi: 10.1093/ndt/gfp005. Epub 2009 Feb 4.
- Background: PubMed 20164820Sewgobind VD, van der Laan LJ, Kho MM, Kraaijeveld R, Korevaar SS, van Dam T, Ijzermans JN, Weimar W, Baan CC. Characterization of rabbit antithymocyte globulins-induced CD25+ regulatory T cells from cells of patients with end-stage renal disease. Transplantation. 2010 Mar 27;89(6):655-66. doi: 10.1097/TP.0b013e3181c9cc7a.
- Background: PubMed 25851286Sharif MR, Chitsazian Z, Moosavian M, Raygan F, Nikoueinejad H, Sharif AR, Einollahi B. Immune disorders in hemodialysis patients. Iran J Kidney Dis. 2015 Mar;9(2):84-96.
- Background: PubMed 21865772Uda S, Mizobuchi M, Akizawa T. Biocompatible characteristics of high-performance membranes. Contrib Nephrol. 2011;173:23-29. doi: 10.1159/000328941. Epub 2011 Aug 8.
- Results publication: PubMed 20157169Libetta C, Esposito P, Sepe V, Portalupi V, Margiotta E, Canevari M, Dal Canton A. Dialysis treatment and regulatory T cells. Nephrol Dial Transplant. 2010 May;25(5):1723-7. doi: 10.1093/ndt/gfq055. Epub 2010 Feb 15. No abstract available.
- Derived from this study: PubMed 31729973Sepe V, Gregorini M, Rampino T, Esposito P, Coppo R, Galli F, Libetta C. Vitamin e-loaded membrane dialyzers reduce hemodialysis inflammaging. BMC Nephrol. 2019 Nov 15;20(1):412. doi: 10.1186/s12882-019-1585-6.
- 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.
Carmelo Libetta, Prof principal investigator
Fondazione Policlinico "San Matteo", Pavia- Italy
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 Haemodialysis Complication and Immune Dysfunction, run by Fondazione IRCCS Policlinico San Matteo di Pavia at 1 site in Italy.
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 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 5 Dec 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 Italy. 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?
Treg number (time frame: Assessment of Treg number at basal control and then every 3 months for a total study period of 12 months). 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 NCT02981992, which also lists 6 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 5 Dec 2016.