NFAT Regulated Gene Expression in Tacrolimus Treated PatientsNCT03315858
NFAT-regulated Gene Expression After Tacrolimus
An observational study of NFAT Regulated Gene Expression in Tacrolimus Treated Patients, run by Medical University of Graz at 1 site in Austria.
Trial summary
Aim of the study is measurement of NFAT-RGE (IL-2 (interleukin-2), IFN-γ (interferon-gamma), GM-CSF (granulocyte monocyte colony stimulating factor)) after tacrolimus (TAC) in de-novo immunosuppressed patients after liver transplantation (LT), to test the hypothesis that in de-novo TAC patients receiving mycophenolate… Read more about this study
- Who is it for?
- Ages 18 to 90 years
- Conditions the study is for
- NFAT Regulated Gene Expression in Tacrolimus Treated Patients
- How many people
- 40 participants
- Where
- 1 siteAustria
- Study dates
- 18 Jan 2019to 29 Nov 2021
- 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 90 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: As a pilot trial this study comprises of 15 patients who will undergo liver transplantation.
Who may be able to join
- Patients > 18 years of age
- Liver transplantation
- Informed consent
Who cannot join
- Patients < 18 of years
- Patients taking actively part in a different interventional trial
Trial locations and contacts
1 site in 1 country.
Austria1 site
Medical University of Graz, Klin. Abteilung für Transplantationschirurgie
Graz, 8036
About this study
Official title: NFAT (Nuclear Factor of Activated T-cells)-Regulated Gene Expression After Tacrolimus -the Basis for Future Tailored Immunosuppression-
Aim of the study is measurement of NFAT-RGE (IL-2 (interleukin-2), IFN-γ (interferon-gamma), GM-CSF (granulocyte monocyte colony stimulating factor)) after tacrolimus (TAC) in de-novo immunosuppressed patients after liver transplantation (LT), to test the hypothesis that in de-novo TAC patients receiving mycophenolate mofetil (MMF) and steroids after LT there is an inverse correlation of NFAT-RGE and TAC peak levels at 1.5 hours after TAC intake.
Read the detailed description
The trial will be conducted as a prospective, longitudinal study. The study is a single-centre study performed at the Medical University of Graz, Department of Surgery, Division of Transplant Surgery and the Department of Blood Group Serology and Transfusion Medicine, Medical University of Graz.
All the patients on the LT wailting list at the Division of Transplant Surgery, Medical University of Graz are screened according to both inclusion and exclusion criteria. The study period is 1 year. One NFAT-RGE baseline measurement is performed directly before LT; NFAT-RGE-measurements after LT are performed at clearly defined timepoints.
Study population. As a pilot trial this study comprises of 15 patients who will undergo LT
Objectives:
- To test the hypothesis that in de-novo TAC patients receiving mycophenolate mofetil (MMF) and steroids after LT there is an inverse correlation of NFAT-RGE and TAC peak levels at 1.5 hours after TAC intake
- To correlate both NFAT-RGE and TAC (trough and peak) levels with rejection episodes and TAC side effects
Approach:
NFAT-RGE is determined in 15 patients just before LT, and after LT after 1 day, 1 week, 2 weeks, and after 1, 6 and 12 months.
Methods. Heparinized peripheral blood is stimulated with 1 ml of complete Roswell Park Memorial Institute (RPMI) 1640 medium containing 100 ng/ml phorbol 12-myristate 13-acetate (PMA) and 5 mcg/ml ionomycin (Sigma-Aldrich Corp., St.Louis, MO, USA) for 3 hours at 37°C. Following ex vivo immune activation, after red cell lysis with ACK buffer (0.15 M NH4CL, 1.0 mM KHCO3), leukocytes are lysed with 400 mcl of MagNA-Pure lysis buffer supplemented with an additional 1% (W/v) of dithiothritol (RAS, Mannheim, Germany), and the sample is frozen at -70°C. After thawing, mRNA is isolated with the RNA Blood mini Kit (Quiagen) device using the mRNA standard protocol for cells. RNA is reverse transcribed using SuperScript III First-Strand Synthesis System for RT-PCR (Invitrogen, life technologies). The 3 NFAT-regulated genes (IFN-γ, IL-2, GM-CSF) were identified as suitable genes for this essay from previous studies [18, 26]. Target mRNA sequences of IFN- γ, IL-2, GM-CSF and 3 reference genes are amplified using commercially available PrimePCR ddPCR Gene Expression Probe Assays (Biorad) by digital PCR (Biorad).
The RGE after TAC intake is calculated as cpeak/c0x100, where c0 is the adjusted number of transcripts at the TAC predose level and cpeak is the number of transcripts 1.5 (c1.5) hours after drug intake.
- Keywords
- NFAT, gene expression, tacrolimus
What is being measured
The primary outcome is the main question the study is designed to answer.
correlation of NFAT-RGE and TAC peak levels
Calculation: cpeak/c0x100
Measured: 1 year
Secondary outcomes (1)
correlation of both NFAT-RGE and TAC (trough and peak) levels with rejection episodes and TAC side effects
Calculation: cpeak/c0x100
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Oct 2017
- Study start18 Jan 2019
- Primary completion29 Nov 2021
- Study completion29 Nov 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for NFAT Regulated Gene Expression in Tacrolimus Treated PatientsStudies of the same condition, open and under way.
- 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
- 40 participants (actual)
Sponsor and investigators
- Lead sponsor
- Medical University of Graz
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03315858
- Sponsor's protocol ID
- NFAT1
- Status last verified
- Feb 2022
- First submitted
- 17 Oct 2017
- Last updated
- 3 Feb 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 3 Feb 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- NFAT (Nuclear Factor of Activated T-cells)-Regulated Gene Expression After Tacrolimus -the Basis for Future Tailored Immunosuppression-
- ClinicalTrials.gov ID
- NCT03315858
- Acronym / sponsor ID
- NFAT1
- Keywords
- NFAT, gene expression, tacrolimus
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 40 participants (actual)
- Lead sponsor
- Medical University of GrazUniversity, hospital or other
- Study start
- 18 Jan 2019 (actual)
- Primary completion
- 29 Nov 2021 (actual)
- Study completion
- 29 Nov 2021 (actual)
- First posted
- 20 Oct 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.
Aim of the study is measurement of NFAT-RGE (IL-2 (interleukin-2), IFN-γ (interferon-gamma), GM-CSF (granulocyte monocyte colony stimulating factor)) after tacrolimus (TAC) in de-novo immunosuppressed patients after liver transplantation (LT), to test the hypothesis that in de-novo TAC patients receiving mycophenolate mofetil (MMF) and steroids after LT there is an inverse correlation of NFAT-RGE and TAC peak levels at 1.5 hours after TAC intake.
Detailed description
The trial will be conducted as a prospective, longitudinal study. The study is a single-centre study performed at the Medical University of Graz, Department of Surgery, Division of Transplant Surgery and the Department of Blood Group Serology and Transfusion Medicine, Medical University of Graz.
All the patients on the LT wailting list at the Division of Transplant Surgery, Medical University of Graz are screened according to both inclusion and exclusion criteria. The study period is 1 year. One NFAT-RGE baseline measurement is performed directly before LT; NFAT-RGE-measurements after LT are performed at clearly defined timepoints.
Study population. As a pilot trial this study comprises of 15 patients who will undergo LT
Objectives:
- To test the hypothesis that in de-novo TAC patients receiving mycophenolate mofetil (MMF) and steroids after LT there is an inverse correlation of NFAT-RGE and TAC peak levels at 1.5 hours after TAC intake
- To correlate both NFAT-RGE and TAC (trough and peak) levels with rejection episodes and TAC side effects
Approach:
NFAT-RGE is determined in 15 patients just before LT, and after LT after 1 day, 1 week, 2 weeks, and after 1, 6 and 12 months.
Methods. Heparinized peripheral blood is stimulated with 1 ml of complete Roswell Park Memorial Institute (RPMI) 1640 medium containing 100 ng/ml phorbol 12-myristate 13-acetate (PMA) and 5 mcg/ml ionomycin (Sigma-Aldrich Corp., St.Louis, MO, USA) for 3 hours at 37°C. Following ex vivo immune activation, after red cell lysis with ACK buffer (0.15 M NH4CL, 1.0 mM KHCO3), leukocytes are lysed with 400 mcl of MagNA-Pure lysis buffer supplemented with an additional 1% (W/v) of dithiothritol (RAS, Mannheim, Germany), and the sample is frozen at -70°C. After thawing, mRNA is isolated with the RNA Blood mini Kit (Quiagen) device using the mRNA standard protocol for cells. RNA is reverse transcribed using SuperScript III First-Strand Synthesis System for RT-PCR (Invitrogen, life technologies). The 3 NFAT-regulated genes (IFN-γ, IL-2, GM-CSF) were identified as suitable genes for this essay from previous studies [18, 26]. Target mRNA sequences of IFN- γ, IL-2, GM-CSF and 3 reference genes are amplified using commercially available PrimePCR ddPCR Gene Expression Probe Assays (Biorad) by digital PCR (Biorad).
The RGE after TAC intake is calculated as cpeak/c0x100, where c0 is the adjusted number of transcripts at the TAC predose level and cpeak is the number of transcripts 1.5 (c1.5) hours after drug intake.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
Who may qualify
- Ages
- 18 to 90 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- As a pilot trial this study comprises of 15 patients who will undergo liver transplantation.
Key inclusion criteria (3 listed)
- Patients > 18 years of age
- Liver transplantation
- Informed consent
Key exclusion criteria (2 listed)
- Patients < 18 of years
- Patients taking actively part in a different interventional trial
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 of NFAT-RGE and TAC peak levels
Time frame: 1 year
Calculation: cpeak/c0x100
1 secondary outcome
correlation of both NFAT-RGE and TAC (trough and peak) levels with rejection episodes and TAC side effects
Time frame: 1 year
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 3 Feb 2022.
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 NFAT Regulated Gene Expression in Tacrolimus Treated Patients, run by Medical University of Graz at 1 site in Austria.
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: finished, as of the sponsor's last update on 3 Feb 2022. 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 Austria. 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?
correlation of NFAT-RGE and TAC peak levels (time frame: 1 year). 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 3 Feb 2022.