Calcineurin Inhibitor (CNI)-Free Immunosuppressive Regimen in T1D Patients Receiving Islet Transplantation

• Status: Completed
• Trial end date: 2012-06-01
• Target enrollment: 0
• Participant gender: All

Summary

Our final objective is to develop an adoptive therapy with tolerogenic donor-specific Tr1 cells in T1D patients undergoing pancreatic islet transplantation (Tx). The achievement of this objective depends by the availability of an immunosuppressive treatment (IS) compatible with the survival, function, and expansion of the transferred Tr1 cells. For this purpose the investigators design a CNI-free single-group, phase 1-2 trial excluding the ATG or anti-CD25 induction therapy after the 1st islet infusion

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Ospedale San Raffaele
• Collaborator: Juvenile Diabetes Research Foundation
• Treatments: Calcineurin Inhibitors; Thymoglobulin

Criteria

Inclusion Criteria:

• Male and female patients aged 18-65yr

• ability to provide written informed consent and comply with the study protocol procedures

• clinical history of type 1 diabetes with onset <40yr of age, on insulin for at least 5yr at the time of enrollment

• absent stimulated C-peptide (<0.5ng/ml) in response to arginine

• multiple (three or more) daily insulin injections or insulin pump therapy

• self blood glucose monitoring ≥3 times/day, supervised by a specialist physician

• high glycemic instability and hypoglycemia unawareness

• inability to consistently attain a HbA1c < 7.5 % target without experiencing severe hypoglycemia (assistance by another person) in the past 36 months despite appropriate medical management.

Exclusion Criteria:

• HbA1c >12%

• BMI >30 kg/m2, or insulin requirement of > 0.8 IU/kg/day;

• poorly controlled hypertension;

• untreated proliferative diabetic retinopathy;

• presence or history of macroalbuminuria (>300mg/g day) or measured glomerular filtration rate <60 ml/min/1.73 m2 for females and <70 ml/min/1.73 m2 for males

• for female participants: positive pregnancy test, presently breast-feeding, or unwilling to use effective contraceptive measures for the duration of the study and 3 months after discontinuation

• for male participants: intent to procreate during the duration of the study or within 3 months after discontinuation or unwillingness to use effective measures of contraception;

• any history of malignancy within the previous 5 years, except for completely resected squamous or basal cell carcinoma of the skin;