ImmunosuppressionINTACTNCT06342505
Tacrolimus in CD3+ T Lymphocytes
An observational study of Immunosuppression, run by Erasmus Medical Center at 1 site in Netherlands.
Trial summary
The goal of this study is to measure concentrations of the drug tacrolimus in both whole blood and within T lymphocytes. It will also learn on the correlation between the concentration in T lymphocytes and the effects of the drug. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Immunosuppression
- What is being tested?
- Venipunctures
- Type of treatment
- Surgery or procedure
- How many people
- 28 participants
- Where
- 1 siteNetherlands
- Study dates
- 30 May 2022to 10 Nov 2022
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Recipients of a kidney transplant at the Erasmus MC who receive routine tacrolimus-based immunosuppression as part of routine clinical care.
Who may be able to join
- Age ≥ 18 years.
- Receive a kidney transplant at Erasmus MC.
- Use once-daily tacrolimus as part of routine maintenance immunosuppression starting the day of surgery.
- Written informed consent.
Who cannot join
- Receive lymphocyte depleting agents (thymoglobulin, anti-thymocyte globulin, and alemtuzumab) as an induction therapy or anti-rejection treatment before the enrolment (lymphocyte depleting agents will lower the amount of CD3+ T lymphocytes to the level that they cannot be isolated for the measurement of intracellular tacrolimus concentration).
Trial locations and contacts
1 site in 1 country.
About this study
Official title: The Intracellular Pharmacokinetics of Tacrolimus in CD3+ T Lymphocytes
The goal of this study is to measure concentrations of the drug tacrolimus in both whole blood and within T lymphocytes. It will also learn on the correlation between the concentration in T lymphocytes and the effects of the drug. The main questions are:
(i) What is the ratio between the tacrolimus concentration within T lymphocytes and in whole blood?; (ii) What is the correlation between tacrolimus concentrations and the effects of the drug?
Participants will:
- Receive standard clinical care;
- Undergo two extra venipunctures for the collection of blood.
Read the detailed description
Rationale: The immunosuppressive drug tacrolimus is routinely monitored after kidney transplantation by measuring the whole blood, pre-dose concentration (C0). However, the C0 has a poor correlation with clinical events, most notably the risk of acute rejection. Since tacrolimus' site of action is within immune cells, the intracellular tacrolimus concentration in peripheral blood mononuclear cells (PBMCs) has recently been proposed to better represent the active concentration. However, several studies could not demonstrate an association between the intracellular tacrolimus concentration and acute rejection. One of the possible explanations for this surprising finding is the fact the PBMC fraction is composed of several cells including lymphocytes and monocytes. In this study, the tacrolimus concentration in CD3+ T lymphocytes will be investigated as this may be a more relevant cell population than PBMCs.
Objective: To prospectively measure the intracellular tacrolimus concentration in CD3+ T lymphocytes in kidney transplant recipients. The area under the concentration-vs-time curve (AUC) of the intracellular tacrolimus concentration will be determined and used for the development of a population pharmacokinetic model. The pharmacokinetics of intra-CD3+ tacrolimus will be compared with the whole-blood concentration and will be related to important clinical events.
Study design: Observational study with additional blood sampling. Study population: Twenty-five de novo kidney transplant recipients receiving once-daily tacrolimus- as maintenance immunosuppression.
Intervention: Two extra venipunctures for the collection of blood.
- Conditions
- Immunosuppression
- Being tested
- Venipunctures
- Keywords
- Pharmacokinetics, Tacrolimus, Kidney transplantation, Intracellular T lymphocyte concentration
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
VenipuncturesProcedure or surgery
Extra venipunctures
| Study group | Role | What they receive |
|---|---|---|
| De novo kidney transplant recipients | Intervention: Two extra venipunctures for the collection of blood. Drug: Once-daily extended-release tacrolimus formulation with a standard, body-weight-based starting dose of 0.14 mg/kg/day Receives: Procedure: Venipunctures |
What is being measured
The primary outcome is the main question the study is designed to answer.
The intracellular tacrolimus concentration in CD3+ T lymphocytes
The tacrolimus concentration in T lymphocytes will be measured by a validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) method. The concentration measured is reported in μg/L. The intracellular tacrolimus concentration will then be calculated and reported in pg/million cells (range 5-1,250 pg/million cells).
Measured: Follow-up to one month post-transplantation
Secondary outcomes (1)
Intracellular cytokine production
=CD3+ T lymphocytes will be stimulated in vivo by CD3/CD28 magnetic beads overnight. Cytokines produced by CD3+ T lymphocytes, including IL-2 and IFN-γ, will be measured by the intracellular staining under flow cytometry.
Measured: Follow-up to one month post-transplantation
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Apr 2024
- Study start30 May 2022
- Primary completion10 Oct 2022
- Study completion10 Nov 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for ImmunosuppressionStudies of the same condition, open and under way.
- More trials run by Erasmus Medical CenterThe 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
- 28 participants (actual)
Sponsor and investigators
- Lead sponsor
- Erasmus Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Dr. B.C.M. (Brenda) de Winter, Erasmus Medical Center
- Investigators
- Brenda C.M. de Winter, PharmD, PhD, Principal investigator, Erasmus Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06342505
- Sponsor's protocol ID
- MEC-2022-0037
- Acronym
- INTACT
- Status last verified
- Mar 2024
- First submitted
- 26 Mar 2024
- Last updated
- 2 Apr 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 2 Apr 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Intracellular Pharmacokinetics of Tacrolimus in CD3+ T Lymphocytes
- ClinicalTrials.gov ID
- NCT06342505
- Acronym / sponsor ID
- INTACT / MEC-2022-0037
- Conditions
- Immunosuppression
- Keywords
- Pharmacokinetics, Tacrolimus, Kidney transplantation, Intracellular T lymphocyte concentration
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 28 participants (actual)
- Lead sponsor
- Erasmus Medical CenterUniversity, hospital or other
- Study start
- 30 May 2022 (actual)
- Primary completion
- 10 Oct 2022 (actual)
- Study completion
- 10 Nov 2022 (actual)
- First posted
- 2 Apr 2024 (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.
The goal of this study is to measure concentrations of the drug tacrolimus in both whole blood and within T lymphocytes. It will also learn on the correlation between the concentration in T lymphocytes and the effects of the drug. The main questions are:
(i) What is the ratio between the tacrolimus concentration within T lymphocytes and in whole blood?; (ii) What is the correlation between tacrolimus concentrations and the effects of the drug?
Participants will:
- Receive standard clinical care;
- Undergo two extra venipunctures for the collection of blood.
Detailed description
Rationale: The immunosuppressive drug tacrolimus is routinely monitored after kidney transplantation by measuring the whole blood, pre-dose concentration (C0). However, the C0 has a poor correlation with clinical events, most notably the risk of acute rejection. Since tacrolimus' site of action is within immune cells, the intracellular tacrolimus concentration in peripheral blood mononuclear cells (PBMCs) has recently been proposed to better represent the active concentration. However, several studies could not demonstrate an association between the intracellular tacrolimus concentration and acute rejection. One of the possible explanations for this surprising finding is the fact the PBMC fraction is composed of several cells including lymphocytes and monocytes. In this study, the tacrolimus concentration in CD3+ T lymphocytes will be investigated as this may be a more relevant cell population than PBMCs.
Objective: To prospectively measure the intracellular tacrolimus concentration in CD3+ T lymphocytes in kidney transplant recipients. The area under the concentration-vs-time curve (AUC) of the intracellular tacrolimus concentration will be determined and used for the development of a population pharmacokinetic model. The pharmacokinetics of intra-CD3+ tacrolimus will be compared with the whole-blood concentration and will be related to important clinical events.
Study design: Observational study with additional blood sampling. Study population: Twenty-five de novo kidney transplant recipients receiving once-daily tacrolimus- as maintenance immunosuppression.
Intervention: Two extra venipunctures for the collection of blood.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| De novo kidney transplant recipients | – | Procedure: VenipuncturesIntervention: Two extra venipunctures for the collection of blood. Drug: Once-daily extended-release tacrolimus formulation with a standard, body-weight-based starting dose of 0.14 mg/kg/day |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Recipients of a kidney transplant at the Erasmus MC who receive routine tacrolimus-based immunosuppression as part of routine clinical care.
Key inclusion criteria (4 listed)
- Age ≥ 18 years.
- Receive a kidney transplant at Erasmus MC.
- Use once-daily tacrolimus as part of routine maintenance immunosuppression starting the day of surgery.
- Written informed consent.
Key exclusion criteria (1 listed)
- Receive lymphocyte depleting agents (thymoglobulin, anti-thymocyte globulin, and alemtuzumab) as an induction therapy or anti-rejection treatment before the enrolment (lymphocyte depleting agents will lower the amount of CD3+ T lymphocytes to the level that they cannot be isolated for the measurement of intracellular tacrolimus concentration).
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 |
|---|---|---|
| VenipuncturesExtra venipunctures | Procedure or surgery | De novo kidney transplant recipients |
Primary outcome
The intracellular tacrolimus concentration in CD3+ T lymphocytes
Time frame: Follow-up to one month post-transplantation
The tacrolimus concentration in T lymphocytes will be measured by a validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) method. The concentration measured is reported in μg/L. The intracellular tacrolimus concentration will then be calculated and reported in pg/million cells (range 5-1,250 pg/million cells).
1 secondary outcome
Intracellular cytokine production
Time frame: Follow-up to one month post-transplantation
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 2 Apr 2024.
- Individual participant dataSharing planned: No
Related trials for Immunosuppression
RecruitingPhase 2
A Study Comparing Siplizumab With Rabbit Anti-Thymocyte Globulin to Help the Body Accept a Kidney Transplant
Renal Transplant Failure and Rejection
Active, not recruitingPhase 3
RSV Vaccine in Transplant Recipients
Vaccine Response Impaired, Respiratory Syncytial Virus Infections
RecruitingObservational study
Metabolic and Functional Study of γδ T Cells in Critically Ill Patients
Sepsis, Critical Illness
Not yet recruitingPhase 1
Study of Disulfiram to Reduce Myeloid Immunosuppression and Steroid Dependence in Resectable High Grade Glioma
Brain (Nervous System) Cancers
Active, not recruitingPhase 2
Islet Cell Transplant for Type 1 Diabetes
Type 1 Diabetes Mellitus
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.
Brenda C.M. de Winter, PharmD, PhD principal investigator
Erasmus Medical Center
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 Immunosuppression, run by Erasmus Medical Center at 1 site in Netherlands.
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 4 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 2 Apr 2024. 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 Netherlands. 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?
The intracellular tacrolimus concentration in CD3+ T lymphocytes (time frame: Follow-up to one month post-transplantation). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 2 Apr 2024.