Posttransplant Diabetes MellitusPhase 4TAGLUMETNCT05396898
Tacrolimus Formulation and Glucose Metabolism After Kidney Transplantation (TAGLUMET Trial)
A Phase 4 study testing LCP-tacrolimus and twice-daily tacrolimus in people with Posttransplant Diabetes Mellitus, run by University Hospital Tuebingen at 1 site in Germany.
Trial summary
Posttransplantation diabetes mellitus after kidney transplantation mediated by tacrolimus is mainly dependent on dose and peak plasma concentration. To substantiate the potential benefits on glucose metabolism and lipid profile of LCP-tacrolimus compared to standard twice-daily tacrolimus after kidney transplantation… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Posttransplant Diabetes Mellitus
- What is being tested?
- LCP-tacrolimus and twice-daily tacrolimus
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 44 participants
- Where
- 1 siteGermany
- Study dates
- 16 Dec 2020to 30 Dec 2023
- Phase
- Phase 4
- 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
- Stable adult kidney transplant recipients on maintenance immunosuppression, >=12 months after kidney transplantation; stable is defined as no need for diagnostic and therapeutic interventions (e.g. kidney biopsy)
- Tacrolimus-based immunosuppression in combination with mycophenolic acid or azathioprine and maintenance prednisolone (<= 5 mg/q.d.) for at least 3 months
- Must be >= 18 years at the time of signing the informed consent
- Understand and voluntarily sign an informed consent document prior to any study related assessments/procedures.
- Able to adhere to the study visit schedule and other protocol requirements.
- Subject (male or female) is willing to use highly effective methods during the study treatment (adequate: combined hormonal contraception associated with inhibition of ovulation, progestogen-only hormonal contraception associated with inhibition of ovulation, intrauterine device, intrauterine hormone-releasing system, bilateral tubal occlusion, vasectomized partner, sexual abstinence).
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- Females of childbearing potential (FCBP) must agree to pregnancy testing within 7 days from 1st dosing of IMP
- To abstain from breastfeeding during study participation and 28 days after study drug discontinuation.
- All subjects must agree not to share medication
Who cannot join
- patients with known diabetes mellitus or PTDM, or HbA1c>=6.5%
- fasting plasma glucose on examination day (visit 1) of >= 126 mg/dl (7,0 mmol/l)
- patients with combined transplantation (e.g. liver-kidney, pancreas-kidney, etc.)
- patients with acute infection at time of baseline visit
- patients with known non-adherence
- patients with rejection therapy or increased dosis of corticosteroids for other reasons within 3 months prior to inclusion.
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- Women during pregnancy and lactation.
- History of hypersensitivity to the investigational medicinal product or to any drug with similar chemical structure or to any excipient present in the pharmaceutical form of the investigational medicinal product.
- Participation in other interventional clinical trials (inclusive of the Follow-up period)
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Conversion to Extended-release MeltDose® Tacrolimus After Kidney Transplantation - Impact on Glucose Metabolism and Lipid Profile
Posttransplantation diabetes mellitus after kidney transplantation mediated by tacrolimus is mainly dependent on dose and peak plasma concentration. To substantiate the potential benefits on glucose metabolism and lipid profile of LCP-tacrolimus compared to standard twice-daily tacrolimus after kidney transplantation, a prospective randomized intraindividual cross-over conversion trial with a comprehensive assessment of glucose metabolism and lipid profile is performed. Primary endpoint is the difference in insulin secretion between treatments, as the principal parameter affected by tacrolimus peak concentrations.
Aim of the study is, to assess glucose metabolism under different tacrolimus formulations (LCP-tacrolimus and twice-daily tacrolimus).
Read the detailed description
Posttransplantation diabetes mellitus (PTDM) is an increasing problem in solid organ transplantation with profound impact on patient and allograft survival. One major contributing factor for the development of PTDM is choice of immunosuppression. Calcineurin inhibitors (CNIs), especially tacrolimus display a substantial diabetogenic potential but remain a cornerstone in maintenance immunosuppression for prevention of rejection and allograft loss. The diabetogenic effect of tacrolimus is mediated predominantly via disturbance of beta-cell function and impaired insulin secretion. There is growing evidence that this effect is dependent on dose and peak plasma concentrations. Once-dailyLCP-tacrolimus has been shown to have lower peak concentrations than twicedaily tacrolimus with comparable efficacy and safety.
LCP-tacrolimus has been shown to improve triglyceride levels, compared to twicedaily tacrolimus. In this study, no effect on the incidence of PTDM was observed, however assessed only by fasting plasma glucose, HbA1c and antidiabetic treatment. As 1/3 of patients with diabetes are solely diagnosed via oral glucose tolerance test, this approach is insufficient for proper evaluation of glucose metabolism, including prediabetes as the principal risk factor.
From pathophysiologic understanding blood lipids and glucose metabolism are strongly associated, as hypertriglyceridemia correlates with insulin resistance. In combination with the lower peak concentrations, it can be hypothesized that LCP-tacrolimus results in better glucose metabolism after kidney transplantation, compared to twicedaily tacrolimus Better understanding of glucose metabolism under different tacrolimus formulations would address a key component of long-term cardiovascular risk and patient outcome after kidney transplantation.
- Conditions
- Posttransplant Diabetes Mellitus
- Being tested
- LCP-tacrolimus, twice-daily tacrolimus
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LCP-tacrolimusDrug
Also called Envarsus®
Prophylaxis of transplant rejection in liver and kidney allograft recipients
twice-daily tacrolimusDrug
Also called Prograf®
Prophylaxis of transplant rejection in liver, kidney or heart allograft recipients
| Study group | Role | What they receive |
|---|---|---|
| LCP-tacrolimus (Envarsus®) | Experimental | Patients in this arm start (after randomization) on LCP-tacrolimus therapy.
At midterm of study participation (16 weeks), a switch is made to twice-daily tacrolimus (Prograf® ) therapy.
The duration of the trial for each subject is expected to be 32 weeks. Receives: Drug: LCP-tacrolimus |
| twice-daily tacrolimus (Prograf®) | Active comparator | Patients in this arm start (after randomization) on twice daily tacrolimus (Prograf®) therapy.
At midterm of study participation (16 weeks), a switch is made to LCP-tacrolimus (Envarsus®) therapy. The duration of the trial for each subject is expected to be 32 weeks. Receives: Drug: twice-daily tacrolimus |
What is being measured
The primary outcome is the main question the study is designed to answer.
Difference in insulin secretion
The Difference in insulin secretion is determined by ratio AUC insulin / AUC glucose during OGTT at timepoints 16 and 32 weeks after randomization in intraindividual treatment crossover.
Measured: 16 and 32 weeks
Secondary outcomes (7)
Differences in parameters of glucose metabolism: fasting plasma glucose
Assessment of fasting plasma glucose determined in [mg/dl].
Measured: 16 and 32 weeks
Differences in parameters of glucose metabolism: OGTT
Assessment of 2h glucose in an extended oral glucose tolerance test (OGTT) determined in [mg/dl].
Measured: 16 and 32 weeks
Differences in parameters of glucose metabolism: insulin sensitivity
Assessment of insulin sensitivity determined in [µmol/l].
Measured: 16 and 32 weeks
Differences in blood lipid levels
Assessment of blood lipid levels determined in [mg/dl].
Measured: 16 and 32 weeks
Allograft function: eGFR
Assessment of eGFR (estimated glomerular filtration rate) determined in [ml/min].
Measured: 16 and 32 weeks
Allograft function: urinary albumin excretion
Assessment of urinary albumin excretion determined in [g/dl].
Measured: 16 and 32 weeks
Drug concentration/dose ratio
Assessment of Drug concentration/dose ratio (C/D Ratio) is determined by
Tacrolimus level [ng/ml] related to the dose of tacrolimus taken orally the previous day [mg]:
C/D Ratio [ng/ml x 1/mg].
Measured: 16 and 32 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 May 2022
- Study start16 Dec 2020
- Primary completion4 Aug 2023
- Study completion30 Dec 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Posttransplant Diabetes MellitusStudies of the same condition, open and under way.
- More trials run by University Hospital TuebingenThe 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 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 44 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospital Tuebingen
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Martina Guthoff, PD Dr., Principal investigator, University Hospital Tuebingen
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05396898
- Sponsor's protocol ID
- TAGLUMET
- Acronym
- TAGLUMET
- Status last verified
- Feb 2024
- First submitted
- 17 May 2022
- Last updated
- 2 Feb 2024
- 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 2 Feb 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Conversion to Extended-release MeltDose® Tacrolimus After Kidney Transplantation - Impact on Glucose Metabolism and Lipid Profile
- ClinicalTrials.gov ID
- NCT05396898
- Acronym / sponsor ID
- TAGLUMET / TAGLUMET
- Conditions
- Posttransplant Diabetes Mellitus
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 44 participants (actual)
- Lead sponsor
- University Hospital TuebingenUniversity, hospital or other
- Study start
- 16 Dec 2020 (actual)
- Primary completion
- 4 Aug 2023 (actual)
- Study completion
- 30 Dec 2023 (actual)
- First posted
- 31 May 2022 (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.
Posttransplantation diabetes mellitus after kidney transplantation mediated by tacrolimus is mainly dependent on dose and peak plasma concentration. To substantiate the potential benefits on glucose metabolism and lipid profile of LCP-tacrolimus compared to standard twice-daily tacrolimus after kidney transplantation, a prospective randomized intraindividual cross-over conversion trial with a comprehensive assessment of glucose metabolism and lipid profile is performed. Primary endpoint is the difference in insulin secretion between treatments, as the principal parameter affected by tacrolimus peak concentrations.
Aim of the study is, to assess glucose metabolism under different tacrolimus formulations (LCP-tacrolimus and twice-daily tacrolimus).
Detailed description
Posttransplantation diabetes mellitus (PTDM) is an increasing problem in solid organ transplantation with profound impact on patient and allograft survival. One major contributing factor for the development of PTDM is choice of immunosuppression. Calcineurin inhibitors (CNIs), especially tacrolimus display a substantial diabetogenic potential but remain a cornerstone in maintenance immunosuppression for prevention of rejection and allograft loss. The diabetogenic effect of tacrolimus is mediated predominantly via disturbance of beta-cell function and impaired insulin secretion. There is growing evidence that this effect is dependent on dose and peak plasma concentrations. Once-dailyLCP-tacrolimus has been shown to have lower peak concentrations than twicedaily tacrolimus with comparable efficacy and safety.
LCP-tacrolimus has been shown to improve triglyceride levels, compared to twicedaily tacrolimus. In this study, no effect on the incidence of PTDM was observed, however assessed only by fasting plasma glucose, HbA1c and antidiabetic treatment. As 1/3 of patients with diabetes are solely diagnosed via oral glucose tolerance test, this approach is insufficient for proper evaluation of glucose metabolism, including prediabetes as the principal risk factor.
From pathophysiologic understanding blood lipids and glucose metabolism are strongly associated, as hypertriglyceridemia correlates with insulin resistance. In combination with the lower peak concentrations, it can be hypothesized that LCP-tacrolimus results in better glucose metabolism after kidney transplantation, compared to twicedaily tacrolimus Better understanding of glucose metabolism under different tacrolimus formulations would address a key component of long-term cardiovascular risk and patient outcome after kidney transplantation.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| LCP-tacrolimus (Envarsus®) | Experimental | Drug: LCP-tacrolimusPatients in this arm start (after randomization) on LCP-tacrolimus therapy. At midterm of study participation (16 weeks), a switch is made to twice-daily tacrolimus (Prograf® ) therapy. The duration of the trial for each subject is expected to be 32 weeks. |
| twice-daily tacrolimus (Prograf®) | Active comparator | Drug: twice-daily tacrolimusPatients in this arm start (after randomization) on twice daily tacrolimus (Prograf®) therapy. At midterm of study participation (16 weeks), a switch is made to LCP-tacrolimus (Envarsus®) therapy. The duration of the trial for each subject is expected to be 32 weeks. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Stable adult kidney transplant recipients on maintenance immunosuppression, >=12 months after kidney transplantation; stable is defined as no need for diagnostic and therapeutic interventions (e.g. kidney biopsy)
- Tacrolimus-based immunosuppression in combination with mycophenolic acid or azathioprine and maintenance prednisolone (<= 5 mg/q.d.) for at least 3 months
- Must be >= 18 years at the time of signing the informed consent
- Understand and voluntarily sign an informed consent document prior to any study related assessments/procedures.
- Able to adhere to the study visit schedule and other protocol requirements.
Key exclusion criteria (9 listed)
- patients with known diabetes mellitus or PTDM, or HbA1c>=6.5%
- fasting plasma glucose on examination day (visit 1) of >= 126 mg/dl (7,0 mmol/l)
- patients with combined transplantation (e.g. liver-kidney, pancreas-kidney, etc.)
- patients with acute infection at time of baseline visit
- patients with known non-adherence
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 |
|---|---|---|
| LCP-tacrolimusAlso: Envarsus®Prophylaxis of transplant rejection in liver and kidney allograft recipients | Drug | LCP-tacrolimus (Envarsus®) |
| twice-daily tacrolimusAlso: Prograf®Prophylaxis of transplant rejection in liver, kidney or heart allograft recipients | Drug | twice-daily tacrolimus (Prograf®) |
Primary outcome
Difference in insulin secretion
Time frame: 16 and 32 weeks
The Difference in insulin secretion is determined by ratio AUC insulin / AUC glucose during OGTT at timepoints 16 and 32 weeks after randomization in intraindividual treatment crossover.
7 secondary outcomes
Differences in parameters of glucose metabolism: fasting plasma glucose
Time frame: 16 and 32 weeks
Differences in parameters of glucose metabolism: OGTT
Time frame: 16 and 32 weeks
Differences in parameters of glucose metabolism: insulin sensitivity
Time frame: 16 and 32 weeks
Differences in blood lipid levels
Time frame: 16 and 32 weeks
Allograft function: eGFR
Time frame: 16 and 32 weeks
Allograft function: urinary albumin excretion
Time frame: 16 and 32 weeks
Drug concentration/dose ratio
Time frame: 16 and 32 weeks
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 Feb 2024.
Related trials for Posttransplant Diabetes Mellitus
RecruitingObservational study
Predicting Outcomes in Posttransplant Diabetes Mellitus Via microRNA
Diabetes Mellitus, Kidney Transplant
Enrolling by invitationPhase 3
Silymarin's Advantage on Graft Effectiveness
Posttransplant Diabetes Mellitus, Acute Graft Rejection
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.
Martina Guthoff, PD Dr. principal investigator
University Hospital Tuebingen
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing LCP-tacrolimus and twice-daily tacrolimus in people with Posttransplant Diabetes Mellitus, run by University Hospital Tuebingen at 1 site in Germany.
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 9 inclusion and 9 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 Feb 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 Germany. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
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?
Difference in insulin secretion (time frame: 16 and 32 weeks). 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 Feb 2024.