Reparixin in Pancreatic Islet Transplantation
Condition: Pancreatic Islet Transplantation in Type 1 Diabetes Mellitus
MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 1
Intervention: Reparixin
Intervention description: Reparixin + immunosuppression
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 9.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: No
Keywords: Islet transplantation; Type 1 diabetes mellitus

Summary:

      Inhibition of CXCL8 activity might represent a relevant therapeutic target to prevent injury
      occurring after pancreatic islet transplantation. Reparixin is a novel and specific inhibitor
      of CXCL8. This study is designed to explore the efficacy of reparixin in preventing graft
      dysfunction after islet transplantation in type 1 diabetes patients (T1D).
    

Eligibility criteria:

        Inclusion criteria:

          -  Ages 18-65 years, inclusive.

          -  Patients eligible for pancreatic islet transplantation based on local accepted
             practice and guidelines. This includes at least: a)clinical history compatible with
             T1D with insulin-dependence for >5 years; b) undetectable stimulated (arginine or
             MMTT) C-peptide levels (<0.3 ng/mL) in the 12 months before transplant. Sites will
             comply with any additional or more stringent criteria locally accepted, as per centre
             practice.

          -  Patients with adequate renal reserve as per calculated creatinine clearance (CLcr) >
             60 mL/min according to the Cockcroft-Gault formula (1976).

          -  Planned intrahepatic islet transplantation alone from a non-living donor with brain
             death.

          -  Planned infusion of 4000 to 7000 islet equivalent (IEQ)/kg body weight.

          -  Patients willing and able to comply with the protocol procedures for the duration of
             the study, including scheduled follow-up visits and examinations.

          -  Patients given written informed consent, prior to any study-related procedure not part
             of normal medical care, with the understanding that consent may be withdrawn by the
             patient at any time without prejudice to their future medical care.

        Exclusion criteria:

          -  Recipients of any previous transplant, except from recipients of a previous pancreatic
             islet transplantation that has failed, are off immunosuppression since at least 1 year
             and have negative anti-HLA.

          -  Recipients of islet from a non-heart beating donor.

          -  A body mass index >30 kg/m2 or patient weight <45 kg.

          -  Pre-transplant average daily insulin requirement >1 IU/kg/day.

          -  Pre-transplant HbA1c >11%.

          -  Patients with hepatic dysfunction as defined by increased ALT/AST > 3 x ULN and
             increased total bilirubin > 3mg/dL [>51.3 micromol/L]).

          -  Patients who receive treatment for a medical condition requiring chronic use of
             systemic steroids.

          -  Treatment with any anti-diabetic medication other than insulin within 4 weeks of
             transplant.

          -  Use of any investigational agent within 4 weeks of enrolment.

          -  Hypersensitivity to:

               -  ibuprofen or to more than one non steroidal anti-inflammatory drug

               -  medications belonging to the class of sulfonamides, such as sulfamethazine,
                  sulfamethoxazole, sulfasalazine, nimesulide or celecoxib.

          -  Pregnant or breast-feeding women; unwillingness to use effective contraceptive
             measures (females and males).

        Sites will comply with any additional exclusion criteria locally accepted, as per centre
        practice.