Pancreatic Transplant
Conditions
Keywords
Immunothrombosis
Brief summary
A prospective, open-label, uncontrolled, non-randomized, single-center Phase I/II clinical trial evaluating the safety of Anakinra in the immediate post-transplant period following pancreatic transplantation
Detailed description
Pancreas transplantation is the treatment of choice for curing diabetes by restoring long-term endogenous insulin secretion. However, the increased risk of rejection compared to other transplants, and especially the risk of early graft loss due to immunological thrombosis, are major obstacles to this procedure. IL-1β blockade is commonly used in islet transplantation, as it has demonstrated a benefit in terms of graft survival when administered immediately postoperatively, in combination with TNFα blockade18. The ILIPO study therefore aims to evaluate the safety of anti-IL-1β treatment as an adjunct to the regimen currently used in our department for pancreatic transplants.
Interventions
Safety of Anakinra in the immediate aftermath of pancreatic transplantation
Sponsors
Nantes University Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
the safety of Anakinra in the immediate aftermath of pancreatic transplantation
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patient admitted to Nantes University Hospital for a pancreatic transplant (alone or combined with a kidney transplant) * Pancreatic graft rank: 1, 2 or 3 * Affiliated with the social security scheme * Written consent to participate in the study * Women must meet one of the following criteria at the time of inclusion: * use adequate contraceptive measures and have a negative pregnancy test (urine test) before receiving the first dose of the trial drug * or be postmenopausal (aged over 50 with amenorrhoea for at least 12 months after stopping all exogenous hormone treatments); * or (if under 50 years of age) have been amenorrhoeic for at least 12 months after stopping exogenous hormone treatments and with luteinising hormone (LH) and follicle-stimulating hormone (FSH) levels corresponding to postmenopausal levels; * or have undergone irreversible surgical sterilisation by hysterectomy, bilateral oophorectomy or bilateral salpingectomy (this operation must be documented). * Male patients with a partner must be willing to use male contraception (condoms) during the trial and for up to 90 days after the last dose of the trial drug. partners of male subjects participating in the trial may use hormonal contraceptives as one of the acceptable methods of contraception, as they will not be receiving the trial drug (i.e., oral hormonal contraception, cap, diaphragm, or sponge with spermicide).
Exclusion criteria
* Patient under guardianship/curatorship * Patient under judicial protection * Pregnant or breastfeeding woman * Positive tuberculin skin test in the last 12 months * Hepatitis B viral replication in the last 12 months * History of known hypersensitivity to Anakinra or any of its excipients or to proteins derived from E. coli * Neutropenia \< 1500/mm3 prior to transplantation (daily assessment) * Patient unable to understand and speak French * Patient participating in another interventional study (outside RIRCM)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| evaluate the safety of IL-1β in a pilot study of patients who have undergone a pancreas transplant | 1 year | Type, severity (CTACAE, and 2012 KDIGO classification for kidney damage) and number (and percentage) of adverse events occurring within the first year following pancreatic transplantation, with a particular focus on severe infections (bacterial, viral, fungal, or parasitic infections that are life-threatening and/or require hospitalization), the occurrence of rejection confirmed by biopsy, and graft survival compared to a historical control cohort (DIVAT Nantes Cohort). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Assess patient survival one year after transplantation | 1 year | Patient survival will be determined by the patients who are still alive one year after pancreatic transplantation. |
| Assess pancreatic graft survival one year post-transplant | 1 year | Pancreatic transplant failure is defined as the occurrence of any of the following criteria within one year of transplantation: The need for daily insulin treatment and/or removal of the pancreatic graft (i.e., pancreatic graft transplantectomy) and/or pancreatic retransplantation and/or islet of Langhans transplantation. |
| Assess pancreatic graft function | 1 year | Assessment of C-peptide (ng/mL) one year after transplantation to calculate the β2 score and IGLS criteria. |
| Assess renal graft function (in the case of simultaneous kidney-pancreas transplantation) | 1 year | Assessment of serum creatinine levels (mmol/24h) one year after simultaneous kidney-pancreas transplantation. |
| Assess the occurrence of severe bacterial infections | up to 1 year | The occurrence of severe bacterial infections, i.e. those requiring hospitalisation. |
| Assess the occurrence of Cytomégalovirus infection | up to 1 year | Occurrence of CMV viremia, whether asymptomatic and/or associated with CMV disease (i.e. organ involvement linked to CMV replication: haematological, gastrointestinal, hepatic or pulmonary). |
| Assess the occurrence of BK virus infection | up to 1 year | Occurrence of BK virus viremia, whether asymptomatic and/or associated with BK virus nephropathy confirmed by biopsy. |
| Assess the occurrence of fungal infection | up to 1 year | — |
| Assess the occurrence of pancreatic graft rejection | up to 1 year | Occurrence of pancreatic rejection confirmed by pancreatic biopsy (according to the Banff criteria) and/or by renal biopsy in the presence of findings consistent with associated pancreatic rejection |
| Assess the occurrence of renal graft rejection (in the case of simultaneous kidney-pancreas transplantation) | up to 1 year | — |
| Assess the occurrence of graft-specific antibodies | 1 year | Development of anti-graft antibodies at one year, considered significant where the Mean Fluorescence Index is \> 500. |
Countries
France
Contacts
CONTACTChristophe MASSET
Outcome results
None listed