Transplantation of immunoprotected pancreatic islets for the therapy of type 1 diabetes mellitus (T1DM)
| ISRCTN | ISRCTN43557935 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN43557935 |
| Secondary identifying numbers | 19382 PRE805 |
- 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
Scientific
University of Perugia
Department of Internal Medicine
Via E. Dal Pozzo
Perugia
06126
Italy
| Phone | +39 347 8000349 |
|---|---|
| islet@unipg.it |
Study information
| Study design | Phase I single-arm single-centre pilot trial |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Hospital |
| Study type | Treatment |
| Participant information sheet | Not available in web format, please use the contact details below to request a patient 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 |
| Pharmaceutical study type(s) | |
| Phase | Phase I |
| Drug / device / biological / vaccine name(s) | Pancreatic islet allografts |
| Primary outcome measure | 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) |
| Secondary outcome measures | 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) |
| Overall study start date | 01/03/2004 |
| Completion date | 01/01/2012 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Sex | Male |
| Target number of participants | 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
06126
Italy
Sponsor information
University of Perugia (Italy)
University/education
University/education
Department of Internal Medicine
Via E. Dal Pozzo
Perugia
06126
Italy
| Phone | +39 075 5723623 |
|---|---|
| fsant@unipg.it | |
| Website | http://www.unipg.it |
"ROR" |
https://ror.org/00x27da85 |
Funders
Funder type
University/education
University of Perugia (Italy)
No information available
Inter-University Consortium for Organ Tranplantation (Italy)
No information available
Results and Publications
| Intention to publish date | |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Not provided at time of registration |
| Publication and dissemination plan | 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 |
