Hepatic TransplantationNCT01388387
Pharmacogenetic Study of Tacrolimus in Hepatic Transplant (CYPTAC'H)
A study testing Tacrolimus pharmacokinetics in people with Hepatic Transplantation, run by Rennes University Hospital at 1 site in France.
Trial summary
The choice of an immunosuppressant after hepatic transplant is now more difficult than before because of the increasing number of drugs available. Pharmacokinetic, pharmacodynamic and pharmacogenetic information can help to choose the best treatment and the best dose for each patient. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Hepatic Transplantation
- What is being tested?
- Tacrolimus pharmacokinetics
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 154 participants
- Where
- 1 siteFrance
- Study dates
- 22 Feb 2012to 31 Jul 2018
- Phase
- Interventional
- 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
Who may be able to join
- Adults (>18 years) of Caucasian origin,
- with hepatic transplant,
- who are going to be treated by tacrolimus, and
- who gave free, well-informed and written consent.
- Non-inclusion Criteria:
- Participation to another protocol incompatible with the study,
- HIV patients with antiretroviral treatment,
- Patients with legal guardianship or deprived of freedom.
Who cannot join
None listed.
Trial locations and contacts
1 site in 1 country.
France1 site
Service des Maladies du Foie - Hôpital de Pontchaillou
Rennes, 35033
About this study
Official title: Impact of Donor and Recipient CYP3A5 Genetic Polymorphism on Tacrolimus Exposure in Patients With Hepatic Transplant
The choice of an immunosuppressant after hepatic transplant is now more difficult than before because of the increasing number of drugs available.
Pharmacokinetic, pharmacodynamic and pharmacogenetic information can help to choose the best treatment and the best dose for each patient. The genetic polymorphism of enzymes metabolizing treatments can affect their efficacy and safety. Concerning tacrolimus, CYP3A5 activity is a major determinant of the dose needed to reach target concentrations. This study is aimed at evaluating the impact of both donor and recipient CYP3A5 genetic polymorphisms on tacrolimus exposure in patients with hepatic transplant.
Read the detailed description
Pharmacogenetics is a recent tool which could help to choose the best immunosuppressive therapy in patients with hepatic transplant. Indeed, the CYP3A5 gene has many polymorphisms and one of them, g.6986 A>G, is the major determinant of the variability of expression of this protein. The allele *1 (g6986A) leads to normal protein expression while the allele *3 (g.6986G) causes lack of protein expression, and their different combinations induce a great variability in tacrolimus concentrations. As cytochromes are present in the liver and intestine, in hepatic transplant, tacrolimus exposure results from both recipient (enterocytes) and donor (liver) enzymes. Recent studies demonstrated a significant role of the genotype recipient on the dose/concentration relationship and on the dose needed to reach target concentrations. However, these studies were insufficient to analyze more precisely all impacts of this polymorphism because they did not include enough patients. The purpose of the investigators study is to evaluate the impact of donor and recipient CYP3A5 genetic polymorphism on tacrolimus exposure in patients with hepatic transplant after the first administration of tacrolimus and at 7 days post transplantation, when the dose has been adapted to avoid too high blood levels and to limit serious adverse reactions.
- Conditions
- Hepatic Transplantation
- Being tested
- Tacrolimus pharmacokinetics
- Keywords
- pharmacogenetics, pharmacokinetics, tacrolimus, genetic polymorphism, CYP3A5, liver transplantation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Tacrolimus pharmacokineticsOther
tacrolimus pharmacokinetics over 12 hours
| Study group | Role | What they receive |
|---|---|---|
| Tacrolimus pharmacokinetics | Experimental | Not described Receives: Other: Tacrolimus pharmacokinetics |
What is being measured
The primary outcome is the main question the study is designed to answer.
Exposure to tacrolimus after the first administration, using tacrolimus area under curve (AUC) between 0 and 12 hours, weighted by the dose administered.
Measured: 12 hours
Secondary outcomes (2)
Pharmacokinetics after the first administration and after 7 days of treatment
Maximal concentration, time needed to reach maximal concentration, residual concentration 12 hours after drug administration, terminal elimination half-life, systemic clearance, AUC 0-12h/dose.
Measured: 7 days
Clinical follow-up during the 3 months post transplantation
Prescribed tacrolimus dose, tolerance of tacrolimus (hypertension, diabetes, renal insufficiency, neurological troubles) and signs of liver rejection assessed at each follow-up visit.
Measured: 3 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Jul 2011 (estimated)
- Study start22 Feb 2012
- Primary completion31 Jul 2018
- Study completion31 Jul 2018
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 Hepatic TransplantationStudies of the same condition, open and under way.
- More trials run by Rennes University 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
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 154 participants (actual)
Sponsor and investigators
- Lead sponsor
- Rennes University Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Eric BELLISSANT, MD, PhD, Study chair, Rennes University HospitalMarie-Clémence VERDIER, PharmD, Study chair, Rennes University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01388387
- Sponsor's protocol ID
- 2010-022488-36
- Other IDs
- CIC0203/129
- Status last verified
- May 2023
- First submitted
- 1 Jul 2011
- Last updated
- 24 May 2023
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Tron C, Woillard JB, Houssel-Debry P, David V, Jezequel C, Rayar M, Balakirouchenane D, Blanchet B, Debord J, Petitcollin A, Roussel M, Verdier MC, Bellissant E, Lemaitre F. Pharmacogenetic-Whole blood and intracellular pharmacokinetic-Pharmacodynamic (PG-PK2-PD) relationship of tacrolimus in liver transplant recipients. PLoS One. 2020 Mar 12;15(3):e0230195. doi: 10.1371/journal.pone.0230195. eCollection 2020.
PubMed 32163483
Study at a glance
From the registry record, last updated by the sponsor on 24 May 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Impact of Donor and Recipient CYP3A5 Genetic Polymorphism on Tacrolimus Exposure in Patients With Hepatic Transplant
- ClinicalTrials.gov ID
- NCT01388387
- Acronym / sponsor ID
- 2010-022488-36
- Conditions
- Hepatic Transplantation
- Keywords
- pharmacogenetics, pharmacokinetics, tacrolimus, genetic polymorphism, CYP3A5, liver transplantation
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 154 participants (actual)
- Lead sponsor
- Rennes University HospitalUniversity, hospital or other
- Study start
- 22 Feb 2012 (actual)
- Primary completion
- 31 Jul 2018 (actual)
- Study completion
- 31 Jul 2018 (actual)
- First posted
- 6 Jul 2011 (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 choice of an immunosuppressant after hepatic transplant is now more difficult than before because of the increasing number of drugs available.
Pharmacokinetic, pharmacodynamic and pharmacogenetic information can help to choose the best treatment and the best dose for each patient. The genetic polymorphism of enzymes metabolizing treatments can affect their efficacy and safety. Concerning tacrolimus, CYP3A5 activity is a major determinant of the dose needed to reach target concentrations. This study is aimed at evaluating the impact of both donor and recipient CYP3A5 genetic polymorphisms on tacrolimus exposure in patients with hepatic transplant.
Detailed description
Pharmacogenetics is a recent tool which could help to choose the best immunosuppressive therapy in patients with hepatic transplant. Indeed, the CYP3A5 gene has many polymorphisms and one of them, g.6986 A>G, is the major determinant of the variability of expression of this protein. The allele *1 (g6986A) leads to normal protein expression while the allele *3 (g.6986G) causes lack of protein expression, and their different combinations induce a great variability in tacrolimus concentrations. As cytochromes are present in the liver and intestine, in hepatic transplant, tacrolimus exposure results from both recipient (enterocytes) and donor (liver) enzymes. Recent studies demonstrated a significant role of the genotype recipient on the dose/concentration relationship and on the dose needed to reach target concentrations. However, these studies were insufficient to analyze more precisely all impacts of this polymorphism because they did not include enough patients. The purpose of the investigators study is to evaluate the impact of donor and recipient CYP3A5 genetic polymorphism on tacrolimus exposure in patients with hepatic transplant after the first administration of tacrolimus and at 7 days post transplantation, when the dose has been adapted to avoid too high blood levels and to limit serious adverse reactions.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Tacrolimus pharmacokinetics | Experimental | Other: Tacrolimus pharmacokinetics |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Adults (>18 years) of Caucasian origin,
- with hepatic transplant,
- who are going to be treated by tacrolimus, and
- who gave free, well-informed and written consent.
- Participation to another protocol incompatible with the study,
Key exclusion criteria (0 listed)
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 |
|---|---|---|
| Tacrolimus pharmacokineticstacrolimus pharmacokinetics over 12 hours | Other | Tacrolimus pharmacokinetics |
Primary outcome
Exposure to tacrolimus after the first administration, using tacrolimus area under curve (AUC) between 0 and 12 hours, weighted by the dose administered.
Time frame: 12 hours
2 secondary outcomes
Pharmacokinetics after the first administration and after 7 days of treatment
Time frame: 7 days
Clinical follow-up during the 3 months post transplantation
Time frame: 3 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 24 May 2023.
- Results publication: PubMed 32163483Tron C, Woillard JB, Houssel-Debry P, David V, Jezequel C, Rayar M, Balakirouchenane D, Blanchet B, Debord J, Petitcollin A, Roussel M, Verdier MC, Bellissant E, Lemaitre F. Pharmacogenetic-Whole blood and intracellular pharmacokinetic-Pharmacodynamic (PG-PK2-PD) relationship of tacrolimus in liver transplant recipients. PLoS One. 2020 Mar 12;15(3):e0230195. doi: 10.1371/journal.pone.0230195. eCollection 2020.
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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.
Eric BELLISSANT, MD, PhD study chair
Rennes University Hospital
Marie-Clémence VERDIER, PharmD study chair
Rennes University Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Tacrolimus pharmacokinetics in people with Hepatic Transplantation, run by Rennes University Hospital at 1 site in France.
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 8 inclusion and 0 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 24 May 2023. 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 France. 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?
Exposure to tacrolimus after the first administration, using tacrolimus area under curve (AUC) between 0 and 12 hours, weighted by the dose administered. (time frame: 12 hours). 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 NCT01388387, 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 24 May 2023.