Kidney TransplantationPhase 2NCT01014234
Rapamycin and Regulatory T Cells in Kidney Transplantation
A Phase 2 study testing Cyclosporins and Rapamycin in people with Kidney Transplantation, run by Fondazione IRCCS Policlinico San Matteo di Pavia at 1 site in Italy.
Trial summary
The immune system response is mediated by the interaction between the antigen presenting cell (APC), CD4+ T helper cells (Th) and CD4+ CD25+ regulatory T cells, a subgroup of CD4+ T cell which express IL-2 receptor (CD25) and the transcriptional factor foxp3. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Kidney Transplantation
- What is being tested?
- Cyclosporins and Rapamycin
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 56 participants
- Where
- 1 siteItaly
- Study dates
- Jul 2008to Jun 2013
- Phase
- Phase 2
- 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
Who may be able to join
- Male and female aged from 18 to 75 years
- Transplanted patients from cadaveric donors
- Patients who has given written informed consensus
Who cannot join
- Legally unable patients
- Patients who have been participated to others studies in the last 3 months
- Addicted to alcohol or smoking
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Rapamycin and Regulatory T Cells in Renal Transplant Patients: a Two-year Randomized Prospective Study
The immune system response is mediated by the interaction between the antigen presenting cell (APC), CD4+ T helper cells (Th) and CD4+ CD25+ regulatory T cells, a subgroup of CD4+ T cell which express IL-2 receptor (CD25) and the transcriptional factor foxp3. Regulatory T cell may contribute to the maintenance of tolerance by suppressing the immune response to normal or tumor associated antigens.
Regulatory T cell emerge from the thymus during ontogenesis and they represent about 10 % of the peripheral Cd4+ t cells.
Read more
Rapamycin is one the most use treatment to prevent renal allograft failure. Differently from calcineurin inhibitors (cyclosporine and tacrolimus), that inhibit T-cell activation through the inhibition of calcineurin activation, rapamycin inhibits cellular proliferation by impairing the progression of the cellular cycle, in particular by interaction with mTOR. Recently Battaglia et al. have demonstrated a Treg amplification in murine CD4+ lymphocytes treated with rapamycin in vitro.
Aim of the study is to evaluate the effect of different immunosuppressive regimens on regulatory T cell and to verify the hypothesis that rapamycin may induce tolerance in kidney transplanted patients, more than cyclosporine treatment.
Read the detailed description
It is two years randomised controlled trial in parallel groups.
It has been resolved to compare different immunosuppressive regimens:
- cyclosporine+ mycophenolate+prednisone
- rapamycin + mycophenolate + prednisone, this treatment should be introduced after one month from renal transplantation.
Patient should visited at month 1-6-12-24 from the transplant. During the control we will reported the following data: physical examination, blood test (blood count, creatinin, BUN, immunosuppressive blood concentration, histological response of surveillance renal biopsy), blood pressure, attendant change of current therapy, pathological variation, or any hospitalisation both ordinary or in DH regimen.
Moreover in all control visit it will be collected a blood sample for evaluation of regulatory t cells.
- Conditions
- Kidney Transplantation
- Being tested
- Cyclosporins, Rapamycin
- Keywords
- Immunosuppressive Agents, Immune system regulation, Regulatory T cells, Rapamycin, Tolerance
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CyclosporinsDrug
Also called Neoral
These patients will undergo maintenance immunosuppressive treatment with cyclosporine + mycophenolate + prednisone according to established clinical practice. The dosage of drugs will be based on evaluations of serum trough levels and it will be adjusted when necessary.
RapamycinDrug
Also called Sirolimus, Rapamune
These patients will undergo maintenance immunosuppressive treatment with rapamycin + mycophenolate + prednisone according to established clinical practice. The dosage of drugs will be based on evaluations of serum trough levels and it will be adjusted when necessary.
| Study group | Role | What they receive |
|---|---|---|
| Rapamycin | Experimental | Maintenance treatment with rapamycin + mycophenolate + prednisone. This treatment will be introduced one month after renal transplantation. Receives: Drug: Rapamycin |
| cyclosporine | Active comparator | Maintenance treatment with cyclosporine + mycophenolate + prednisone. This treatment will be introduced one month after renal transplantation. Receives: Drug: Cyclosporins |
What is being measured
The primary outcome is the main question the study is designed to answer.
The absolute number of T-reg after renal transplant in patients in treatment with rapamycin compared to patients treated with cyclosporine
Measured: Every 6 months after the transplantation
Secondary outcomes (1)
Adverse events developed during the duration of the clinical study, that damage the patient, that is not part of the natural history of the disease.
Measured: Every two months during the follow-up
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Nov 2009 (estimated)
- Study startJul 2008
- Primary completionJun 2013
- Study completionJun 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Kidney TransplantationStudies 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
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 56 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
- Antonio Dal Canton, MD, Principal investigator, Policlinico Fondazione IRCCS "San Matteo", Pavia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01014234
- Sponsor's protocol ID
- 20070034809
- Status last verified
- Mar 2015
- First submitted
- 13 Nov 2009
- Last updated
- 25 Mar 2015
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Battaglia M, Stabilini A, Migliavacca B, Horejs-Hoeck J, Kaupper T, Roncarolo MG. Rapamycin promotes expansion of functional CD4+CD25+FOXP3+ regulatory T cells of both healthy subjects and type 1 diabetic patients. J Immunol. 2006 Dec 15;177(12):8338-47. doi: 10.4049/jimmunol.177.12.8338.
PubMed 17142730San Segundo D, Fernandez-Fresnedo G, Ruiz JC, Rodrigo E, Benito MJ, Arias M, Lopez-Hoyos M. Two-year follow-up of a prospective study of circulating regulatory T cells in renal transplant patients. Clin Transplant. 2010 May-Jun;24(3):386-93. doi: 10.1111/j.1399-0012.2009.01086.x. Epub 2009 Sep 11.
PubMed 19744094Ramirez E, Morales JM, Lora D, Mellado M, Cevey M, Alfaro FJ, De Pablos P, Andres A, Paz-Artal E, Serrano A. Peripheral blood regulatory T cells in long-term kidney transplant recipients. Transplant Proc. 2009 Jul-Aug;41(6):2360-2. doi: 10.1016/j.transproceed.2009.05.007.
PubMed 19715919
Study at a glance
From the registry record, last updated by the sponsor on 25 Mar 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Rapamycin and Regulatory T Cells in Renal Transplant Patients: a Two-year Randomized Prospective Study
- ClinicalTrials.gov ID
- NCT01014234
- Acronym / sponsor ID
- 20070034809
- Conditions
- Kidney Transplantation
- Keywords
- Immunosuppressive Agents, Immune system regulation, Regulatory T cells, Rapamycin, Tolerance
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 56 participants (actual)
- Lead sponsor
- Fondazione IRCCS Policlinico San Matteo di PaviaUniversity, hospital or other
- Study start
- Jul 2008
- Primary completion
- Jun 2013 (actual)
- Study completion
- Jun 2013 (actual)
- First posted
- 16 Nov 2009 (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.
The immune system response is mediated by the interaction between the antigen presenting cell (APC), CD4+ T helper cells (Th) and CD4+ CD25+ regulatory T cells, a subgroup of CD4+ T cell which express IL-2 receptor (CD25) and the transcriptional factor foxp3. Regulatory T cell may contribute to the maintenance of tolerance by suppressing the immune response to normal or tumor associated antigens.
Regulatory T cell emerge from the thymus during ontogenesis and they represent about 10 % of the peripheral Cd4+ t cells.
Rapamycin is one the most use treatment to prevent renal allograft failure. Differently from calcineurin inhibitors (cyclosporine and tacrolimus), that inhibit T-cell activation through the inhibition of calcineurin activation, rapamycin inhibits cellular proliferation by impairing the progression of the cellular cycle, in particular by interaction with mTOR. Recently Battaglia et al. have demonstrated a Treg amplification in murine CD4+ lymphocytes treated with rapamycin in vitro.
Aim of the study is to evaluate the effect of different immunosuppressive regimens on regulatory T cell and to verify the hypothesis that rapamycin may induce tolerance in kidney transplanted patients, more than cyclosporine treatment.
Detailed description
It is two years randomised controlled trial in parallel groups.
It has been resolved to compare different immunosuppressive regimens:
- cyclosporine+ mycophenolate+prednisone
- rapamycin + mycophenolate + prednisone, this treatment should be introduced after one month from renal transplantation.
Patient should visited at month 1-6-12-24 from the transplant. During the control we will reported the following data: physical examination, blood test (blood count, creatinin, BUN, immunosuppressive blood concentration, histological response of surveillance renal biopsy), blood pressure, attendant change of current therapy, pathological variation, or any hospitalisation both ordinary or in DH regimen.
Moreover in all control visit it will be collected a blood sample for evaluation of regulatory t cells.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Rapamycin | Experimental | Drug: RapamycinMaintenance treatment with rapamycin + mycophenolate + prednisone. This treatment will be introduced one month after renal transplantation. |
| cyclosporine | Active comparator | Drug: CyclosporinsMaintenance treatment with cyclosporine + mycophenolate + prednisone. This treatment will be introduced one month after renal transplantation. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Male and female aged from 18 to 75 years
- Transplanted patients from cadaveric donors
- Patients who has given written informed consensus
Key exclusion criteria (3 listed)
- Legally unable patients
- Patients who have been participated to others studies in the last 3 months
- Addicted to alcohol or smoking
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 |
|---|---|---|
| CyclosporinsAlso: NeoralThese patients will undergo maintenance immunosuppressive treatment with cyclosporine + mycophenolate + prednisone according to established clinical practice. The dosage of drugs will be based on evaluations of serum trough levels and it will be adjusted when necessary. | Drug | cyclosporine |
| RapamycinAlso: Sirolimus, RapamuneThese patients will undergo maintenance immunosuppressive treatment with rapamycin + mycophenolate + prednisone according to established clinical practice. The dosage of drugs will be based on evaluations of serum trough levels and it will be adjusted when necessary. | Drug | Rapamycin |
Primary outcome
The absolute number of T-reg after renal transplant in patients in treatment with rapamycin compared to patients treated with cyclosporine
Time frame: Every 6 months after the transplantation
1 secondary outcome
Adverse events developed during the duration of the clinical study, that damage the patient, that is not part of the natural history of the disease.
Time frame: Every two months during the follow-up
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 25 Mar 2015.
- Background: PubMed 17142730Battaglia M, Stabilini A, Migliavacca B, Horejs-Hoeck J, Kaupper T, Roncarolo MG. Rapamycin promotes expansion of functional CD4+CD25+FOXP3+ regulatory T cells of both healthy subjects and type 1 diabetic patients. J Immunol. 2006 Dec 15;177(12):8338-47. doi: 10.4049/jimmunol.177.12.8338.
- Background: PubMed 19744094San Segundo D, Fernandez-Fresnedo G, Ruiz JC, Rodrigo E, Benito MJ, Arias M, Lopez-Hoyos M. Two-year follow-up of a prospective study of circulating regulatory T cells in renal transplant patients. Clin Transplant. 2010 May-Jun;24(3):386-93. doi: 10.1111/j.1399-0012.2009.01086.x. Epub 2009 Sep 11.
- Background: PubMed 19715919Ramirez E, Morales JM, Lora D, Mellado M, Cevey M, Alfaro FJ, De Pablos P, Andres A, Paz-Artal E, Serrano A. Peripheral blood regulatory T cells in long-term kidney transplant recipients. Transplant Proc. 2009 Jul-Aug;41(6):2360-2. doi: 10.1016/j.transproceed.2009.05.007.
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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.
Antonio Dal Canton, MD principal investigator
Policlinico Fondazione IRCCS "San Matteo", Pavia
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Cyclosporins and Rapamycin in people with Kidney Transplantation, 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 3 inclusion and 3 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 25 Mar 2015. 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.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
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?
The absolute number of T-reg after renal transplant in patients in treatment with rapamycin compared to patients treated with cyclosporine (time frame: Every 6 months after the transplantation). 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 NCT01014234, which also lists 3 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 25 Mar 2015.