Open-label Investigation of the Safety and Effectiveness of DIABECELL(R) in Patients With Type I Diabetes Mellitus
Condition: Type 1 Diabetes
MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 1
Study type: Interventional
Phase: Phase 1/Phase 2

Summary: 
      The purpose of this study is to establish the safety of xenotransplantation of
      DIABECELL(R)[immunoprotected (alginate-encapsulated) porcine islets] in patients with
      established type 1 diabetes mellitus, and to establish preliminary evidence of the efficacy
      of DIABECELL(R), as measured by a reduction in serial hemoglobin A1c (HbA1C) levels.
    

Detailed description: 
      Intraperitoneal islet transplantation has the potential to ameliorate type 1 diabetes
      mellitus and avert the long-term consequences of chronic diabetes which cannot be achieved by
      conventional insulin treatment.

      As donor human islets are not available in sufficient numbers, porcine islets are the best
      alternative source as they are recognised as the most physiologically compatible xenogeneic
      insulin-producing cells. Although the use of pig-derived cells raises the risk of xenotic
      infections, this can be minimised by obtaining cells from designated pathogen-free (DPF)
      animals bred in isolation and monitored to be free of specified pathogens. The worldwide
      experience to date in more than 200 patients who have received transplants of pig tissue has
      not demonstrated evidence of transmitted xenotic infections.

      As animal-derived tissues have to be protected from immune rejection when transplanted into
      humans, transplants are usually accompanied by immunosuppressive therapy. However, porcine
      islets are preferably transplanted without the use of immunosuppressive drugs which cause
      significant morbidity. To protect them from immune rejection, the islets can be encapsulated
      in alginate microcapsules which permit the inward passage of nutrients and glucose and the
      outward passage of insulin. Alginate-encapsulated porcine islets transplanted without
      immunosuppressive drugs have survived rejection for many months in animal studies, and have
      been retrieved from a diabetic patient over 9.5 years after intraperitoneal transplantation
      and shown to contain viable islets that stain positive for insulin.

      DIABECELL® comprises neonatal porcine islets encapsulated in alginate microcapsules.
      DIABECELL® has been safely transplanted in healthy and diabetic mice, rats, rabbits, dogs and
      non-human primates. Following DIABECELL® transplants, the requirement for daily insulin was
      significantly reduced in diabetic rats and non-human primates.

      The optimal dose and frequency of transplantation of the current DIABECELL® preparation for
      the treatment of type 1 diabetes in humans can only be determined in clinical trials. The
      intention of this phase I/IIa clinical trial is to obtain at least 52 weeks safety and
      preliminary efficacy data in type 1 diabetic patients following transplantation of a single
      low effective dose of DIABECELL® into the peritoneal cavity.
    

Intervention name(s): DIABECELL(R); DIABECELL(R); DIABECELL(R); DIABECELL(R)
Intervention type(s): Device; Device; Device; Device
Intervention description(s): 10,000 IEQ/kg injected into the peritoneal cavity via laparoscopy; 15,000 IEQ/kg injected into the peritoneal cavity via laparoscopy; 20,000 IEQ/kg injected into the peritoneal cavity via laparoscopy; 5,000 IEQ/kg injected into the peritoneal cavity via laparoscopy
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: xenotransplantation; type I diabetes; porcine islets