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Summary

for people ages 18 years and up (full criteria)
at San Francisco, California and other locations
study started
estimated completion:

Description

Summary

The study will be a phase 2/3, multicenter, double-blind, parallel assignment study. It will involve 100 adult recipients of an intra-hepatic pancreatic Islet Auto-Transplantation (IAT). The objective of this clinical trial is to assess whether reparixin leads to improved transplant outcome as measured by the proportion of insulin-independent patients following IAT. The safety of reparixin in the specific clinical setting will be also evaluated.

Official Title

A Phase 2/3, Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel Assignment Study to Assess the Efficacy and Safety of Reparixin in Pancreatic Islet Auto-transplantation

Details

In contrast to allo-transplantation in type 1 diabetes patients, where immunological mechanisms involving allo- and auto-antibodies affect long-term graft function, outcome in IAT (Islet Auto-Transplantation) is independent from immunological processes and does not require immunosuppression management. On the other hand, early inflammatory events intrinsic to the intra-portal islet infusion have been demonstrated to impact islet engraftment. Among possible mechanisms, PMNs have been found to be the predominant cell types infiltrating the liver in a syngeneic model of islet transplantation in mice.

Data obtained in experimental models of islet transplantation in mice demonstrate a clear effect of reparixin in improving graft survival and function. Protection from the loss and/or deterioration of transplanted islets was evident regardless of the immunological mechanisms involved in islet damage, suggesting that the ability of reparixin to modulate early inflammatory responses readily impact graft outcome.

Thus, the use of reparixin may emerge as a potential useful medication in the control of non specific inflammatory events surrounding the early phases of IAT.

The goal of this study is to reach a total of 100 adult patients who are randomized and receive IAT after total or completion pancreatectomy. Patients will be randomly (1:1) assigned to receive either reparixin [continuous i.v. infusion for 7 days (168hrs)], or matched placebo (control group),starting approximately 12hrs before islet infusion. The two groups will be balanced within each centre. All patients who are randomized and receive the Investigational Product (either reparixin or placebo) will be inlcuded in the ITT analysis. Patients will be in the ITT analysis whether or not they receive IAT, because exclusions cannot be made for events occurring after randomization that could be influenced by the randomized assignment.

Recruitment will be competitive among the study sites, until the planned number of patients is enrolled. Competitive recruitment has been chosen to increase the speed of recruitment and to account for any difference in transplant rate among study sites. Each centre will enroll patients as rapidly as possible, up to a maximum of 40 patients (as per the randomization list).

Each patient will be involved in the study for 7 day hospital stay during pancreatectomy followed by islet transplantation, for all required measurements up to hospital discharge and for 2 post-transplant visits scheduled @ day 75+14 and 365+14 after the transplant.

Keywords

Pancreatectomy for Chronic Pancreatitis Pancreatic islet auto-transplantation Pharmaceutical Solutions

Eligibility

You can join if…

Open to people ages 18 years and up

  • Patients eligible for an IAT following total (or completion) pancreatectomy.
  • Ages > 18 years.
  • Patients willing and able to comply with the protocol procedures for the duration of the study, including scheduled follow-up visits and examinations.
  • Patients who have 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.

You CAN'T join if...

  • Recipients of a previous IAT (if completion pancreatectomy).
  • Patients undergoing total pancreatectomy due to either pancreatic cancer or pancreatic benign diseases other than chronic pancreatitis, including insulinomas, etc.
  • Patients with inadequate renal reserve as per calculated creatinine clearance (CLcr) <60 mL/min according to the Cockcroft-Gault formula (1976).
  • Patients with hepatic dysfunction as defined by increased ALT/AST > 3 x upper limit of normal (ULN) or increased total bilirubin above the upper limit at local laboratory).Patients with Gilbert's syndrome (elevated unconjugated bilirubin levels in the absence of any evidence of hepatic or biliary tract disease) are not excluded.
  • Patients with a preoperative International Normalized Ratio (INR) > 1.5 or any known coagulopathy.
  • Hypersensitivity to:
  • ibuprofen or to more than one non steroidal anti-inflammatory drug (NSAID).
  • medications belonging to the class of sulfonamides, such as sulfamethazine,sulfamethoxazole, sulfasalazine, nimesulide or celecoxib.
  • Concurrent sepsis (as per positive blood culture(s) and/or fever associated with other signs of systemic sepsis syndrome).
  • Treatment with systemic steroids in the 2 weeks prior to enrolment (except for the use of <5mg prednisone daily or equivalent dose of hydrocortisone, for physiological replacement only) or with any immune modulators in the 4 weeks prior to enrolment.
  • Patients with pre-existing diabetes or evidence of impaired β-cells function, based on pre-operative fasting blood glucose >115 mg/dL and/or a HbA1c > 6.5%, or requiring treatment with any anti-diabetic medication (e.g. insulin, metformin, etc) within the 2 weeks prior to enrolment.
  • Use of any investigational agent in the 4 weeks prior to enrolment, including any anti-cytokine/chemokine agents.
  • Pregnant or breast-feeding women; unwillingness to use effective contraceptive measures (females and males). (NB: pregnancy should be avoided in patients or partners during the first month after completing the treatment with the Investigational Product; no other specific warnings are described, considering the treatment course of the Investigational Product, its PK profile, and the lack of significant adverse effects on mating performance and fertility in animal studies).
  • Patients with past or current history of alcohol abuse based on clinical history and/or past treatment for alcohol addiction.
  • Patients with evidence of pre-operative portal hypertension as per clinical history and abdominal/liver imaging by ultrasound techniques.

Sites will comply with any additional or more restrictive exclusion criteria locally accepted, as per centre practice.

Locations

  • University of Alberta, Clinical Islet Transplant Program
    Edmonton, Alberta, T6G 2C8, Canada
  • Baylor University Medical Center
    Dallas, Texas, 75246, United States
  • Schulze Diabetes Institute University of Minnesota Medical School
    Minneapolis, Minnesota, 55455, United States
  • The University of Chicago Medical Center
    Chicago, Illinois, 60637, United States
  • The University of Cincinnati Medical Center
    Cincinnati, Ohio, 45219, United States
  • Thomas E. Starzl Transplantation Institute University of Pittsburgh Medical Center
    Pittsburgh, Pennsylvania, 15213, United States
  • Medical University of South Carolina
    Charleston, South Carolina, 29425, United States
  • Dartmouth-Hitchcock Medical Center
    Lebanon, New Hampshire, 03756, United States

Details

Status
in progress, not accepting new patients
Start Date
Completion Date
(estimated)
Sponsor
Dompé Farmaceutici S.p.A
ID
NCT01967888
Phase
Phase 2/3
Lead Scientist
Andrew Posselt
Study Type
Interventional
Last Updated
January 1, 2017