Islet transplantation at the onset of diabetes mellitus type 1

• Conditions: Type 1 diabetes; Therapeutic area: Body processes [G] - Metabolic Phenomena [G03]; MedDRA version: 17.1Level: PTClassification code 10067584Term: Type 1 diabetes mellitusSystem Organ Class: 10027433 - Metabolism and nutrition disorders

• Registration Number: EUCTR2014-004110-28-IT
• Lead Sponsor: IRCCS Ospedale San Raffaele

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2014-12-22
• Last Update Posted: 10 July 2015

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 6

Inclusion Criteria

Males and females aged 18-45 years
- Ability to provide written informed consent
- Mentally stable and able to comply with the procedures of the Protocol for the duration of the study, including follow-up visits and examinations scheduled
- T1D new onset (diagnosis of diabetes within 180 days prior to enrollment).
- Function beta cell residual (C-peptide fasting> 0.3 ng / mL in plasma glucose levels> 70 mg / dL and =200 mg / dL).
- Positivity for at least one of the following autoantibodies typically associated with T1D: anti-GAD, anti-IA-2, anti ZnT8, IAA. A person who is positive for IAA and negative for other autoantibodies is not admissible if used insulin for more than 7 days.
- Ongoing treatment with insulin, or has required insulin therapy (for 7 days) for diabetes at some time between the date of diagnosis and recruitment
- Incompatibility for MHC class IA and B and compatibility for MHC class II DR with the donor of islet

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 6
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

- Body mass index (BMI) = 32.0 kg / m2 or patient = 50kg weight
- Requirement of insulin> 1.0 IU / kg / day
- HbA1c> 10%
- Blood pressure: systolic> 160 mmHg or diastolic blood pressure> 100 mmHg.
- Chronic disease than type 1 diabetes.
- Moderate and severe renal impairment (creatinine clearance <90 mL / min)
- Presence or history of macroalbuminuria (> 300 mg / g creatinine).
- Hepatic dysfunction defined by an increase in ALT / AST above the limit of the normal value and increases in total bilirubin> 3 mg / dl
- Pregnant or breast-feeding.
- Reluctance to use effective contraception up to 4 months after the end of the administration of the study drug (females and males)
- Active infection including hepatitis B, hepatitis C, HIV or tuberculosis (TB). Positive tests are acceptable only if associated with a history of previous vaccination in the absence of any sign of active infection.
- Negative for Epstein-Barr Virus (EBV) to the determination of IgG
- Invasive aspergillosis, histoplasmosis, coccidioidomycosis year prior to study enrollment
- Any history of malignancy except basal or squamous cell carcinoma of the skin eradicated
- Alcohol or substance abuse known active
- Haemoglobin base below the lower limit of normal; lymphopenia (<1,000 / microL), neutropenia (<1,500 / microL), or thrombocytopenia (platelets <100,000 / microL).
- A history of lack of factor V
- Any coagulopathy or diseases requiring long-term anticoagulant therapy (eg, warfarin) after transplantation (treatment with low-dose aspirin is permitted) or patients with an international normalized ratio (INR)> 1.5
- Heart Disease serious coexisting:
recent myocardial infarction (within the last 6 months)
left ventricular ejection fraction <30%
- Calculus symptomatic gallbladder
- Acute or chronic pancreatitis
- Peptic ulcer symptomatic
- Severe diarrhea incessant vomiting or other gastrointestinal disorders potentially interfering with the ability to absorb oral medications
- Hyperlipidemia despite medical therapy (fasting low-density lipoprotein [LDL] cholesterol> 130 mg / dL, treated or untreated, and or fasting triglycerides> 200 mg / dL)
- Treatment for a medical condition requiring chronic use of systemic steroids, except for the use of 5 mg of prednisone per day, or an equivalent dose of hydrocortisone, for the replacement saline.
- Treatment with any anti-diabetic drug other than insulin within 4 weeks of enrollment
- Use of investigational drugs within 4 weeks of enrollment.
- The administration of live attenuated vaccine within 2 months thereafter
- Any medical condition that, in the opinion of the investigator, would interfere with the safe participation in the study.
- Treatment with any immunosuppressive regimen at enrollment

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: The aim of this study is to test the efficacy and safety of a marginal islet transplantation associated with immunosuppressive treatment / modulatory transient therapy for type 1 diabetes onset;Secondary Objective: - Assess the impact of treatment on the immune response of memory and autoimmune in new onset type 1 diabetes<br>- Identify biomarkers that reflect the sensitivity or resistance to the potential benefits of treatment on ß-cell function<br>;Primary end point(s): Change from baseline in the insulin secretory response evaluated as Area Under the Curve (AUC) to two hours of C-peptide plasma in response to mixed meal (MMTT)<br>The incidence and severity of adverse events (AE) on the procedure for islet transplantation or treatment-related immunosuppressive;Timepoint(s) of evaluation of this end point: Week 52 ± 2<br>Weeks 4 ± 1, 12± 2 and week 52 ± 2

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): Change from baseline in the insulin secretory response evaluated as Area Under the Curve (AUC) to two hours of C-peptide plasma in response to mixed meal (MMTT) one year after transplant<br>Change from baseline C-peptide stimulated (the highest value at any point in time during the MMTT after injection mixed meal)<br>Change from baseline in the secretory response gucagone evaluated as Area Under the Curve (AUC) to two hours of C-peptide plasma in response to mixed meal (MMTT);Timepoint(s) of evaluation of this end point: Weeks: 4 ± 1, 12± 2, 26±2 <br>Weeks: 4 ± 1, 12± 2, 26±2, 52 ± 2<br>Weeks: 4±1, 12±2, 26±2, 52±2