Condition category
Nutritional, Metabolic, Endocrine
Date applied
18/03/2009
Date assigned
30/06/2009
Last edited
30/06/2009
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Not provided at time of registration

Trial website

Contact information

Type

Scientific

Primary contact

Prof Riccardo Calafiore

ORCID ID

Contact details

University of Perugia
Department of Internal Medicine
Via E. Dal Pozzo
Perugia
06126
Italy
+39 347 8000349
islet@unipg.it

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

19382 PRE805

Study information

Scientific title

Microencapsulated pancreatic islet allografts into nonimmunosuppressed patients with type 1 diabetes mellitus: a phase I single-arm single-centre pilot trial

Acronym

Study hypothesis

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

1. Italian Ministry of Health, approved on 05/09/2003
2. Ethics Committee of University of Perugia, approved on 15/01/2004

Study design

Phase I single-arm single-centre pilot trial

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Not available in web format, please use the contact details below to request a patient information sheet

Condition

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 names

Pancreatic islet allografts

Primary outcome measures

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 trial start date

01/03/2004

Overall trial end date

01/01/2012

Reason abandoned

Eligibility

Participant 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)

Participant type

Patient

Age group

Adult

Gender

Male

Target number of participants

10

Participant 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

Recruitment start date

01/03/2004

Recruitment end date

01/01/2012

Locations

Countries of recruitment

Italy

Trial participating centre

University of Perugia
Perugia
06126
Italy

Sponsor information

Organisation

University of Perugia (Italy)

Sponsor details

Department of Internal Medicine
Via E. Dal Pozzo
Perugia
06126
Italy
+39 075 5723623
fsant@unipg.it

Sponsor type

University/education

Website

http://www.unipg.it

Funders

Funder type

University/education

Funder name

University of Perugia (Italy)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Funder name

Inter-University Consortium for Organ Tranplantation (Italy)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

2006 results for first two cases in http://www.ncbi.nlm.nih.gov/pubmed/16373911

Publication citations

  1. Results for first two cases

    Calafiore R, Basta G, Luca G, Lemmi A, Montanucci MP, Calabrese G, Racanicchi L, Mancuso F, Brunetti P, Microencapsulated pancreatic islet allografts into nonimmunosuppressed patients with type 1 diabetes: first two cases., Diabetes Care, 2006, 29, 1, 137-138.

Additional files

Editorial Notes