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Reparixin in Pancreatic Islet Transplantation

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Dompé Farmaceutici S.p.A
ClinicalTrials.gov Identifier:
NCT01220856
First received: October 7, 2010
Last updated: June 27, 2014
Last verified: June 2014
October 7, 2010
June 27, 2014
July 2010
September 2012   (Final data collection date for primary outcome measure)
  • The proportion of insulin-independent patients following a single donor-single islet cell transplantation [ Time Frame: day 75 +/- 5 post-transplant ]
  • The proportion of insulin-independent patients after a single donor-single islet cell transplantation [ Time Frame: up to one year after the transplant ]
  • Time to achieve insulin-independence after the transplant [ Time Frame: up to 1 year after the transplant ]
  • Total time of insulin independence after the transplant [ Time Frame: up to 1 year after the transplant ]
  • Change in average daily insulin requirements (absolute and % decrease from pre-transplant levels) [ Time Frame: month 1-3-6-12 post- transplant ]
  • HbA1c (absolute and % decrease from pre-transplant levels) [ Time Frame: month 1-3-6-12 post- transplant ]
  • The proportion of patients free of severe hypoglycaemic events [ Time Frame: month 1-3-6-12 post- transplant ]
  • The proportion of patients free of hypoglycaemic events with reduced awareness [ Time Frame: month 1-3-6-12 post- transplant ]
  • Basal (fasting) and -10 to 120 min time course of glucose, C-peptide and insulin derived from the mixed meal tolerance test [ Time Frame: month 1-3-6-12 post- transplant ]
  • Beta-cell function as assessed by beta-score and Transplant Estimated Function [ Time Frame: month 1-3-6-12 post- transplant ]
  • The proportion of insulin-independent patients following a single donor-single islet cell transplantation [ Time Frame: day 75 +/- 5 post-transplant ]
  • The proportion of insulin-independent patients after a single donor-single islet cell transplantation [ Time Frame: up to one year after the transplant ]
  • Time to achieve insulin-independence after the transplant [ Time Frame: up to 1 year after the transplant ]
  • Total time of insulin independence after the transplant [ Time Frame: up to 1 year after the transplant ]
  • Change in average daily insulin requirements (absolute and % decrease from pre-transplant levels) [ Time Frame: month 1 post- transplant ]
  • HbA1c (absolute and % decrease from pre-transplant levels) [ Time Frame: month 1 post- transplant ]
  • The proportion of patients free of severe hypoglycaemic events [ Time Frame: month 1 post- transplant ]
  • The proportion of patients free of hypoglycaemic events with reduced awareness [ Time Frame: month 1 post- transplant ]
  • Basal (fasting) and -10 to 120 min time course of glucose, C-peptide and insulin derived from the mixed meal tolerance test [ Time Frame: month 1 post- transplant ]
  • Beta-cell function as assessed by beta-score and Transplant Estimated Function [ Time Frame: month 1 post- transplant ]
  • Change in average daily insulin requirements (absolute and % decrease from pre-transplant levels) [ Time Frame: month 3 post-transplant ]
  • Change in average daily insulin requirements (absolute and % decrease from pre-transplant levels) [ Time Frame: month 6 post-transplant ]
  • Change in average daily insulin requirements (absolute and % decrease from pre-transplant levels) [ Time Frame: month 12 post-transplant ]
  • HbA1c (absolute and % decrease from pre-transplant levels) [ Time Frame: month 3 post-transplant ]
  • HbA1c (absolute and % decrease from pre-transplant levels) [ Time Frame: month 6 post-transplant ]
  • HbA1c (absolute and % decrease from pre-transplant levels) [ Time Frame: month 12 post-transplant ]
  • The proportion of patients free of severe hypoglycaemic events [ Time Frame: monh 3 post-transplant ]
  • The proportion of patients free of severe hypoglycaemic events [ Time Frame: month 6 post-transplant ]
  • The proportion of patients free of severe hypoglycaemic events [ Time Frame: month 12 post-transplant ]
  • The proportion of patients free of hypoglycaemic events with reduced awareness [ Time Frame: month 3 post-transplant ]
  • The proportion of patients free of hypoglycaemic events with reduced awareness [ Time Frame: month 6 post-transplant ]
  • The proportion of patients free of hypoglycaemic events with reduced awareness [ Time Frame: month 12 post-transplant ]
  • Beta-cell function as assessed by beta-score and Transplant Estimated Function [ Time Frame: month 3 post-transplant ]
  • Beta-cell function as assessed by beta-score and Transplant Estimated Function [ Time Frame: month 6 post-transplant ]
  • Beta-cell function as assessed by beta-score and Transplant Estimated Function [ Time Frame: month 12 post-transplant ]
  • Basal (fasting) and -10 to 120 min time course of glucose, C-peptide and insulin derived from the mixed meal tolerance test [ Time Frame: month 3 post-transplant ]
  • Basal (fasting) and -10 to 120 min time course of glucose, C-peptide and insulin derived from the mixed meal tolerance test [ Time Frame: month 6 post-transplant ]
  • Basal (fasting) and -10 to 120 min time course of glucose, C-peptide and insulin derived from the mixed meal tolerance test [ Time Frame: month 12 post-transplant ]
Complete list of historical versions of study NCT01220856 on ClinicalTrials.gov Archive Site
  • Incidence and severity of Adverse Events and Serious Adverse Events [ Time Frame: up to 1 year after transplant ]
  • Standard laboratory tests (hematology, clinical chemistry, coagulation) [ Time Frame: day -1 pre-transplant ]
  • Blood pressure and heart rate [ Time Frame: day -1 pre-transplant ]
  • ALT/AST, PT/PTT, fibrin degradation products, C-reactive protein [ Time Frame: daily up to day 6 post-transplant ]
  • Time course of inflammatory chemokines/cytokines [ Time Frame: day -1 pre-transplant ]
  • Plasma levels of reparixin and its major metabolite [ Time Frame: day 3 and day 7 of drug infusion ]
  • Standard laboratory tests (hematology, clinical chemistry, coagulation) [ Time Frame: day 6/7 post-transplant ]
  • Blood pressure and heart rate [ Time Frame: day 6/7 post-transplant ]
  • ALT/AST [ Time Frame: month 1-3 post-transplant ]
  • Time course of inflammatory chemokines/cytokines [ Time Frame: 6-12-24--72-120-168 hrs after islet infusion ]
  • Auto-antibodies and anti-HLA antibodies [ Time Frame: day -1 pre-transplant ]
  • Auto-antibodies and anti-HLA antibodies [ Time Frame: day 6/7 post- transplant; month 1-3-6-12 post- transplant ]
  • Incidence and severity of Adverse Events and Serious Adverse Events [ Time Frame: up to 1 year after transplant ]
  • Standard laboratory tests (hematology, clinical chemistry, coagulation) [ Time Frame: day -1 pre-transplant ]
  • Blood pressure and heart rate [ Time Frame: day -1 pre-transplant ]
  • ALT/AST, PT/PTT, fibrin degradation products, C-reactive protein [ Time Frame: daily up to day 6 post-transplant ]
  • Time course of inflammatory chemokines/cytokines [ Time Frame: day -1 pre-transplant ]
  • Plasma levels of reparixin and its major metabolite [ Time Frame: day 3 and day 7 of drug infusion ]
  • Standard laboratory tests (hematology, clinical chemistry, coagulation) [ Time Frame: day 6/7 post-transplant ]
  • Blood pressure and heart rate [ Time Frame: day 6/7 post-transplant ]
  • ALT/AST [ Time Frame: month 1 post-transplant ]
  • ALT/AST [ Time Frame: month 3 post-transplant ]
  • Time course of inflammatory chemokines/cytokines [ Time Frame: 6hrs after islet infusion ]
  • Time course of inflammatory chemokines/cytokines [ Time Frame: 12hrs after islet infusion ]
  • Time course of inflammatory chemokines/cytokines [ Time Frame: 24hrs after islet infusion ]
  • Time course of inflammatory chemokines/cytokines [ Time Frame: 72hrs after islet infusion ]
  • Time course of inflammatory chemokines/cytokines [ Time Frame: 120hrs after islet infusion ]
  • Time course of inflammatory chemokines/cytokines [ Time Frame: 168hrs after islet infusion ]
  • Auto-antibodies and anti-HLA antibodies [ Time Frame: day -1 pre-transplant ]
  • Auto-antibodies and anti-HLA antibodies [ Time Frame: day 6/7 post- transplant ]
  • Auto-antibodies and anti-HLA antibodies [ Time Frame: month 1 post- transplant ]
  • Auto-antibodies and anti-HLA antibodies [ Time Frame: month 3 post- transplant ]
  • Auto-antibodies and anti-HLA antibodies [ Time Frame: month 6 post- transplant ]
  • Auto-antibodies and anti-HLA antibodies [ Time Frame: month 12 post- transplant ]
Not Provided
Not Provided
 
Reparixin in Pancreatic Islet Transplantation
A Phase 2 Multicenter, Randomized, Open Label, Parallel Assignment, Pilot Study to Assess the Efficacy and Safety of Reparixin Following Islet Transplantation in Patients With Type 1 Diabetes Mellitus
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).
Pancreatic islet transplantation has become a feasible option in the treatment of T1D which offers advantages over whole pancreas transplantation. However to date insulin independence can be obtained in most cases only after the patient has received repeated infusions from several donors. A non-specific immune response, mediated predominantly by innate inflammatory processes, coupled with specific cellular immune responses, possibly promoted by early inflammation, play a major role in the loss of transplanted islets from the liver. PMNs have been found to be the predominant cell types infiltrating in vitro the islets. In this regard, CXCL8 has been shown to be expressed by human islets and could play a crucial role in triggering the inflammatory reaction. Thus, CXCL8 might represent a relevant therapeutic target to prevent early graft failure. The efficacy of reparixin in improving graft outcome in mice models of intrahepatic islet transplantation, as well as the safety shown in human phase 1 and 2 studies, provide a rationale for a clinical study aimed at evaluating the effect of reparixin in preventing graft dysfunction after islet transplantation in T1D patients.
Interventional
Phase 2
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Pancreatic Islet Transplantation in Type 1 Diabetes Mellitus
Drug: Reparixin
Reparixin + immunosuppression
  • Experimental: Reparixin
    Reparixin + Immunosuppression
    Intervention: Drug: Reparixin
  • No Intervention: No experimental intervention
    Immunosuppression only
Citro A, Cantarelli E, Piemonti L. Anti-inflammatory strategies to enhance islet engraftment and survival. Curr Diab Rep. 2013 Oct;13(5):733-44. doi: 10.1007/s11892-013-0401-0. Review.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
9
June 2014
September 2012   (Final data collection date for primary outcome measure)

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.

Sexes Eligible for Study: All
18 Years to 65 Years   (Adult)
No
Contact information is only displayed when the study is recruiting subjects
Germany,   Italy
 
 
NCT01220856
REP0110
2010-019424-31 ( EudraCT Number )
No
Not Provided
Not Provided
Dompé Farmaceutici S.p.A
Dompé Farmaceutici S.p.A
Not Provided
Principal Investigator: Lorenzo Piemonti, MD Fondazione Centro San Raffaele del Monte Tabor - Milan; Italy
Principal Investigator: Barbara Ludwig, MD University Hospital Carl Gustav Carus - Dresden; Germany
Dompé Farmaceutici S.p.A
June 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP