Kidney TransplantationNCT03425071
Monitoring Concentration and Pharmacodynamic Effects of Tacrolimus in Peripheral Blood Lymphocytes of Kidney Transplant Recipients
An observational study of Kidney Transplantation and Rejection, run by University of Sao Paulo General Hospital at 1 site in Brazil.
Trial summary
Therapeutic drug monitoring (TDM) of immunosuppressive drugs is used to improve the immunosuppressive effect while minimizing the toxicity related to exposition to high serum levels. Read more about this study
- Who is it for?
- Ages 18 to 60 yearsHealthy volunteers can take part
- Conditions the study is for
- Kidney Transplantation, Rejection
- How many people
- 45 participants
- Where
- 1 siteBrazil
- Study dates
- 8 Mar 2016to Dec 2018
- 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 60 years
- All sexes
- Healthy volunteers accepted
- Adult
Study population: The study will include kidney transplant recipients followed at Hospital das Clínicas da Faculdade de Medicina da USP.
Who may be able to join
- Kidney transplant recipients with a well functioning graft (serum creatinine ≤ 2,0 mg/dL at inclusion)
- Must be on tacrolimus therapy
- Must be on short term follow up time (1 to 5 months) after surgery
Who cannot join
- A concomitant second solid organ transplant
- Immunosuppression not containing tacrolimus
Trial locations and contacts
1 site in 1 country.
Brazil1 site, 1 recruiting
- Recruiting
Hospital das Clínicas - University of Sao Paulo
São Paulo, São Paulo, 05403900
Nelson Z Galante, PhD, +551126618089, nelson.galante@hc.fm.usp.br
Fabiana Agena, PhD, +551126618089, fabiana.agena@hc.fm.usp.br
About this study
Official title: Monitoring Intracellular Concentration and Pharmacodynamic Effects of Tacrolimus in Peripheral Blood T CD4+ and B CD19+ Lymphocytes of Kidney Transplant Recipients
Therapeutic drug monitoring (TDM) of immunosuppressive drugs is used to improve the immunosuppressive effect while minimizing the toxicity related to exposition to high serum levels. Although TDM is widely used in clinical practice, a significant number of kidney transplant recipients have acute allograft rejection in the first year after transplantation. To improve the use of immunosuppressive drugs, new approaches of TDM have been developed. Monitoring drug concentrations at lymphocytes of peripheral blood is considering promising because it indicates the availability of the drug directly in the target sites of immunosuppression. The present study intends to establish the concentration profile of tacrolimus in the peripheral blood in parallel with the concentration profile inside T and B lymphocytes of peripheral blood of kidney transplant recipients, and correlates them with the expected pharmacological effects. The pharmacological effects of tacrolimus in calcineurin dependent and calcineurin independent (mitogen-activated protein kinase (MAPK) dependent) activation pathways will be assessed by measuring activated nuclear factor of activated T cells (NFAT) and p38, respectively, by flow cytometry. The expression of interleukin (IL) - 2 and IL-10 by T and B lymphocytes, respectively, will be also used to monitoring the pharmacodynamic effects of tacrolimus.
- Conditions
- Kidney Transplantation, Rejection
- Keywords
- Tacrolimus, T Lymphocytes, B lymphocytes, Monitoring, Immunologic
- Medical subject headings
- Rejection, Psychology
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 |
|---|---|---|
| Healthy volunteers | Healthy volunteers - subjects without exposure to tacrolimus. Blood samples from these subjects will be used in "in vitro" experiments. | |
| kidney transplant (KTx) months 1-2 | Kidney transplant recipients recruited during the months 1 to 2 of follow up after kidney transplantation surgery. These are subjects expected to be exposed to high blood levels of tacrolimus. Blood samples from these subjects will be used in "ex vivo" experiments. | |
| KTx months 4-5 | Kidney transplant recipients recruited during the months 4 to 5 of follow up after kidney transplantation surgery. These are subjects expected to be exposed to standard blood levels of tacrolimus. Blood samples from these subjects will be used in "ex vivo" experiments. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Correlation between blood and intracellular levels of tacrolimus
The concentration of tacrolimus will be determined in the whole blood, in T CD4+ cell suspension and in B CD19+ cell suspension prepared from one blood sample per patient subject. The correlations among concentrations of tacrolimus in the 3 different cell matrices will be established.
Measured: From 1 up to 5 months post transplantation
Secondary outcomes (1)
Correlation among intracellular levels of tacrolimus and its pharmacological effects
The pharmacological effects of tacrolimus will be measured as the inhibition of the nuclear translocation of NFAT transcription factor, the phosphorylation state of p38 MAP kinase and the production of interleukin 2 and 10 by flow cytometry.
Measured: From 1 up to 5 months post transplantation
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Feb 2018
- Study start8 Mar 2016
- Primary completionJul 2018 (estimated)
- Study completionDec 2018 (estimated)
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 Kidney TransplantationStudies of the same condition, open and under way.
- More trials run by University of Sao Paulo General HospitalThe 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 only
- Time perspective
- Cross-sectional
- Enrolment
- 45 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Sao Paulo General Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Maria da Luz Fernandes, Paschoalina Romano, Persio de Almeida Rezende Ebner, Nairo Massakazu Sumita, Veronica Porto Carreiro de Vasconcelos Coelho, Fabiana Agena, Elias David Neto, Nelson Zocoler Galante
- Responsible party
- Sponsor
- Investigators
- Nelson Z Galante, PhD, Principal investigator, Kidney Transplantation Service - University of Sao Paulo
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03425071
- Sponsor's protocol ID
- CAAE 41558915900000068
- Status last verified
- Jan 2018
- First submitted
- 30 Jan 2018
- Last updated
- 7 Feb 2018
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Romano P, da Luz Fernandes M, de Almeida Rezende Ebner P, Duarte de Oliveira N, Mitsue Okuda L, Agena F, Mendes ME, Massakazu Sumita N, Coelho V, David-Neto E, Zocoler Galante N. UPLC-MS/MS assay validation for tacrolimus quantitative determination in peripheral blood T CD4+ and B CD19+ lymphocytes. J Pharm Biomed Anal. 2018 Apr 15;152:306-314. doi: 10.1016/j.jpba.2018.01.002. Epub 2018 Jan 5.
PubMed 29471254
Study at a glance
From the registry record, last updated by the sponsor on 7 Feb 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Monitoring Intracellular Concentration and Pharmacodynamic Effects of Tacrolimus in Peripheral Blood T CD4+ and B CD19+ Lymphocytes of Kidney Transplant Recipients
- ClinicalTrials.gov ID
- NCT03425071
- Acronym / sponsor ID
- CAAE 41558915900000068
- Conditions
- Kidney Transplantation, Rejection
- Keywords
- Tacrolimus, T Lymphocytes, B lymphocytes, Monitoring, Immunologic
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 45 participants (estimated)
- Lead sponsor
- University of Sao Paulo General HospitalUniversity, hospital or other
- Collaborators
- Maria da Luz Fernandes, Paschoalina Romano, Persio de Almeida Rezende Ebner, Nairo Massakazu Sumita, Veronica Porto Carreiro de Vasconcelos Coelho, Fabiana Agena, Elias David Neto, Nelson Zocoler Galante
- Study start
- 8 Mar 2016 (actual)
- Primary completion
- Jul 2018 (estimated)
- Study completion
- Dec 2018 (estimated)
- First posted
- 7 Feb 2018 (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.
Therapeutic drug monitoring (TDM) of immunosuppressive drugs is used to improve the immunosuppressive effect while minimizing the toxicity related to exposition to high serum levels. Although TDM is widely used in clinical practice, a significant number of kidney transplant recipients have acute allograft rejection in the first year after transplantation. To improve the use of immunosuppressive drugs, new approaches of TDM have been developed. Monitoring drug concentrations at lymphocytes of peripheral blood is considering promising because it indicates the availability of the drug directly in the target sites of immunosuppression. The present study intends to establish the concentration profile of tacrolimus in the peripheral blood in parallel with the concentration profile inside T and B lymphocytes of peripheral blood of kidney transplant recipients, and correlates them with the expected pharmacological effects. The pharmacological effects of tacrolimus in calcineurin dependent and calcineurin independent (mitogen-activated protein kinase (MAPK) dependent) activation pathways will be assessed by measuring activated nuclear factor of activated T cells (NFAT) and p38, respectively, by flow cytometry. The expression of interleukin (IL) - 2 and IL-10 by T and B lymphocytes, respectively, will be also used to monitoring the pharmacodynamic effects of tacrolimus.
Study design
- Observational model
- Case only
- Time perspective
- Cross-sectional
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Healthy volunteers | – | –Healthy volunteers - subjects without exposure to tacrolimus. Blood samples from these subjects will be used in "in vitro" experiments. |
| kidney transplant (KTx) months 1-2 | – | –Kidney transplant recipients recruited during the months 1 to 2 of follow up after kidney transplantation surgery. These are subjects expected to be exposed to high blood levels of tacrolimus. Blood samples from these subjects will be used in "ex vivo" experiments. |
| KTx months 4-5 | – | –Kidney transplant recipients recruited during the months 4 to 5 of follow up after kidney transplantation surgery. These are subjects expected to be exposed to standard blood levels of tacrolimus. Blood samples from these subjects will be used in "ex vivo" experiments. |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
- Study population
- The study will include kidney transplant recipients followed at Hospital das Clínicas da Faculdade de Medicina da USP.
Key inclusion criteria (3 listed)
- Kidney transplant recipients with a well functioning graft (serum creatinine ≤ 2,0 mg/dL at inclusion)
- Must be on tacrolimus therapy
- Must be on short term follow up time (1 to 5 months) after surgery
Key exclusion criteria (2 listed)
- A concomitant second solid organ transplant
- Immunosuppression not containing tacrolimus
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
Correlation between blood and intracellular levels of tacrolimus
Time frame: From 1 up to 5 months post transplantation
The concentration of tacrolimus will be determined in the whole blood, in T CD4+ cell suspension and in B CD19+ cell suspension prepared from one blood sample per patient subject. The correlations among concentrations of tacrolimus in the 3 different cell matrices will be established.
1 secondary outcome
Correlation among intracellular levels of tacrolimus and its pharmacological effects
Time frame: From 1 up to 5 months post transplantation
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Feb 2018.
- Results publication: PubMed 29471254Romano P, da Luz Fernandes M, de Almeida Rezende Ebner P, Duarte de Oliveira N, Mitsue Okuda L, Agena F, Mendes ME, Massakazu Sumita N, Coelho V, David-Neto E, Zocoler Galante N. UPLC-MS/MS assay validation for tacrolimus quantitative determination in peripheral blood T CD4+ and B CD19+ lymphocytes. J Pharm Biomed Anal. 2018 Apr 15;152:306-314. doi: 10.1016/j.jpba.2018.01.002. Epub 2018 Jan 5.
- 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.
Nelson Z Galante, PhD principal investigator
Kidney Transplantation Service - University of Sao Paulo
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 Kidney Transplantation and Rejection, run by University of Sao Paulo General Hospital at 1 site in Brazil.
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 2 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: status not confirmed, as of the sponsor's last update on 7 Feb 2018. 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 Brazil. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Fabiana Agena, PhD (+551126618089, fabiana.agena@hc.fm.usp.br), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Correlation between blood and intracellular levels of tacrolimus (time frame: From 1 up to 5 months post 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 NCT03425071, 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 7 Feb 2018.