Open-label Investigation of the Safety and Effectiveness of DIABECELL(R) in Patients With Type I Diabetes Mellitus

Phase 1

Completed

• Conditions: Type 1 Diabetes
• Interventions: Device: DIABECELL(R)

• Registration Number: NCT00940173
• Lead Sponsor: Diatranz Otsuka Limited

Brief 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.

Study Timeline

• Study Start: 2009-07
• Study First Submitted: 2009-07-12
• Study First Submitted QC: 2009-07-14
• Study First Posted: 2009-07-15
• Primary Completion: 2013-10
• Study Completion: 2013-10
• Status Verified: 2017-10
• Last Update Submitted: 2017-10-18
• Last Update Posted: 2017-10-20

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 16

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Group 1	DIABECELL(R)	Dose Group 1 (Receiving a dose of 10,000 IEQ/kg of DIABECELL(R))
Group 3	DIABECELL(R)	Dose Group 3 (Receiving a dose of 20,000 IEQ/kg of DIABECELL(R))
Group 2	DIABECELL(R)	Dose Group 2 (Receiving a dose of 15,000 IEQ/kg of DIABECELL(R))
Group 4	DIABECELL(R)	Dose Group 4 (Receiving a dose of 5,000 IEQ/kg of DIABECELL(R))

Primary Outcome Measures

Name	Time	Method
To establish the safety of xenotransplantation of DIABECELL(R) [immunoprotected (alginate-encapsulated) porcine islets]	52 Weeks
To establish preliminary evidence of the efficacy of DIABECELL(R), as measured by a reduction in serial HbA1C levels	52 weeks

Secondary Outcome Measures

Name	Time	Method
To establish whether DIABECELL(R) causes an improvement in glucose lability determined from continuous glucose monitoring	52 Weeks
To determine whether DIABECELL(R) causes a reduction in hypoglycaemia and nocturnal hypoglycaemia	52 Weeks
To determine whether DIABECELL(R) causes a reduction in insulin dose	52 Weeks
To determine whether DIABECELL(R) causes an improvement in endogenous insulin secretion	52 Weeks
To determine whether DIABECELL(R) causes an improvement in quality-of-life	52 Weeks

Trial Locations

Locations (1)

Centre for Clinical Research and Effective Practice; 🇳🇿 Auckland, New Zealand