Transplantation of immunoprotected pancreatic islets for the therapy of type 1 diabetes mellitus (T1DM)

ISRCTN	ISRCTN43557935
DOI	https://doi.org/10.1186/ISRCTN43557935
Protocol serial number	19382 PRE805
Sponsor	University of Perugia (Italy)
Funders	University of Perugia (Italy), Inter-University Consortium for Organ Tranplantation (Italy)

Submission date: 18/03/2009
Registration date: 30/06/2009
Last edited: 30/06/2009

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Nutritional, Metabolic, Endocrine

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Plain English summary of protocol

Not provided at time of registration

Contact information

Prof Riccardo Calafiore
Scientific

University of Perugia
Department of Internal Medicine
Via E. Dal Pozzo
Perugia
06126
Italy

Phone	+39 347 8000349
Email	islet@unipg.it

Study information

Primary study design	Interventional
Study design	Phase I single-arm single-centre pilot trial
Secondary study design	Randomised controlled trial
Study type	Participant information sheet
Scientific title	Microencapsulated pancreatic islet allografts into nonimmunosuppressed patients with type 1 diabetes mellitus: a phase I single-arm single-centre pilot trial
Study objectives	Pancreatic islet allografts into patients with type 1 diabetes mellitus (T1DM) are subject to both immune rejection and autoimmune recurrency of disease if the recipients are not adequately and generally immunosuppressed. Unfortunately most of immunosuppressive agents, whether are they of pharmacological or biological nature are associated with severe, attending risk for serious complications, at level of different organs and apparatuses. In order to circumvent need for the recipint's general immunosuppression we had developed since the mid '80s a method to envelop the isolated islets within highly biocompatible and selective permeable microcapsules, based on alginic acid (a polysaccharide extracted from brown seaweeds) and aminoacidic polycations. Such microcapsules, implemented over the years have been extensively employed in pre-clinical trials where either low or high mammal animal models with either induced or spontaneous diabetes underwent graft of microencapsulated islets. The particular nature and composition of the capsules make these artificial shields very suitable for easy injection in the recipients' peritoneal cavity, with no induction, due to their high biocompatibility, of any inflammatory cell response. The positive results obtained in rodents with spontaneous diabetes (nonobese diabetic [NOD] mice) where encapsulated islet xenografts (rat to mouse; pig to mouse; human to mouse) were able to reverse hyperglycemia for extraordinary long periods of time prompted us to scale up to dogs, and recently mokeys with spontaneous or induced diabetes. Also in these higher mammals positive results were obtained in terms of both, correction of hyperglycemia and absence of inflammatory cell overgrowth of the capsules. Having completed the pre-clinicals we turned our attention to humans. In order to make our capsules suitable for human application we have upscaled our system for ultrapurification of the basic capsules' constituent (alginic acid) so as to obtain a pyrogen-free, endotoxin-free alginic acid (according to FDA guidelines) that is low in protein content (<0.4%, according to the 'bioinvisibility' criterion laid out by FDA).
Ethics approval(s)	1. Italian Ministry of Health, approved on 05/09/2003 2. Ethics Committee of University of Perugia, approved on 15/01/2004
Health condition(s) or problem(s) studied	Type 1 diabetes mellitus
Intervention	Graft of human pancreatic islet containing microcapsules made of alginic acid and poly-L-ornithine. Upon an overnight insulin feed-back, in order to achieve and sustain normoglycemia, the patients undergo, under local anesthesia and echography guidance, a samll abdominal incision to allow passage of a 14G polyethylene catheter connected to a 60 ml syringe luer. The capsules (packed tissue volume = 50 ml) upon suspension in sterile saline will be slowly injected (10 min) through the syringe into the patient's peritoneal cavity. Echography monitoring of the process is insured. Upon termination of the procedure the capsules are visualised echographycally. The trial is taking place at the University of Perugia Hospital and Clinics.
Intervention type	Drug
Phase	Phase I
Drug / device / biological / vaccine name(s)	Pancreatic islet allografts
Primary outcome measure(s)	1. Blood glucose (by reflectometer)hourly the first 7 days, thereafter 4 times a day as per usual clinical protocols for diabetes care 2. Serum C-peptide (radioimmunoassay) hourly the first 7 days, thereafter once a week in basal and 30 min after meal, throughout 2 years 3. Abdominal CT scan (1-6 months)
Key secondary outcome measure(s)	1. Blood glucose levels. Timepionts: hourly during the first 72 hours post-transplant, thereafter 6 times a day until 2 years post-transplantation (end of protocol) 2. Serum C-peptide. Timepoints: hourly during the first 72 hours and thereafter twice a day until 2 weeks post-transplantation (basal, 60 min after breakfast), thereafter once a day (60 min after breakfast) for 3 months, thereafter once monthly (basal + 60 min after breakfast) for 2 years 3. Depending upon obtained blood glucose control (and insulin/C-peptide output) exogenous insulin may be tapered down until suspension if necessary 4. CT scan of the abdomen every 6 months for 2 years 5. The following will be checked regularly until 2 years post-transplantation in order to assess any eventual favourable impact of the encapsulated islet grafts on secondary complications of T1DM: 5.1. Retinography 5.2. Nerve motor and sensorial conduction velocity 5.3. Microalbuminuria (24 hour urines)
Completion date	01/01/2012

Eligibility

Participant type(s)	Patient
Age group	Adult
Sex	Male
Target sample size at registration	10
Key inclusion criteria	1. Male patients, age range: 20-50 years 2. Patients with long-standing T1DM (over 15 years) 3. On daily quadruple insulin injection therapy regimen 4. No major complications of the disease (pre-proliferative retinopathy, initial microalbuminuria, macrovascular disease)
Key exclusion criteria	1. Female patients (because the capsules were to be implanted intraperitoneally, with possible adverse effects on ovary's function) 2. Patients with advanced complcations of T1DM 3. Patients with neoplasms whatsoever
Date of first enrolment	01/03/2004
Date of final enrolment	01/01/2012

Locations

Countries of recruitment

Italy

Study participating centre

University of Perugia

Perugia
06126
Italy

Results and Publications

Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not provided at time of registration
IPD sharing plan

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Results article	results for first two cases	01/01/2006		Yes	No
Participant information sheet	Participant information sheet	11/11/2025	11/11/2025	No	Yes