Long-term Function of Beta Cell Allografts in Non-uremic Type 1 Diabetic Patients

• Status: Unknown status
• Trial end date: 2014-12-01
• Target enrollment: 0
• Participant gender: All

Summary

The present proof of concept study addresses the following specific aims:

The general objectives of this work are:

1. To increase and maintain the functional beta-cell mass after islet transplantation under a condition of low-dose tacrolimus

2. To co-investigate the potential of alternative sites for encapsulated beta-cells

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

Details

• Lead Sponsor: AZ-VUB
• Treatments: Rituximab

Criteria

Inclusion Criteria:

• Age 18-65 years, male or female, Caucasian or not; only subjects < 50 yrs will be allocated to the rituximab treatment arm

• Body weight < 100 kg; patients with a bodyweight of < 80kg, will receive priority

• Patients with a BMI ≤ 27 kg/m2 will receive priority

• Type 1 insulin-dependent diabetes

• C-peptide < 0.07 nmol/l (<0.2 µg/l) 6 min. after glucagon IV (1mg) (glycemia > 180 mg/dl)

• Intensive insulin therapy for more than two years, patients with insulin pump during at least 2 months before inclusion will receive priority

• Patients should have at least one of the following chronic complications of diabetes:

• Plasma creatinine <2 mg/dl and albuminuria 30-1000 mg/ 24hrs on 3 separate determinations (>1 month) outside an episode of illness, despite intake of ACE inhibitors; mean systolic blood pressure should be under 130 mmHg and mean diastolic blood pressure under 85 mmHg, when measured at home with ambulatory BP monitoring

• Moderate or severe non-proliferative or proliferative retinopathy

• Hypoglycemic unawareness

• Cooperative and reliable patient giving informed consent by signature

Exclusion Criteria:

• Smoker

• EBV antibody negativity

• HIV 1 & 2 antibody positivity

• CMV IgM positivity

• Plasma creatinine ≥ 2 mg/dl and/or albuminuria ≥1000 mg/24 hrs

• History of thrombosis or pulmonary embolism

• History of malignancy, tuberculosis or chronic viral hepatitis

• History of any other serious illness which could be relevant for the protocol

• Presence of HLA antibodies

• Blood donation within one month prior to screening or during the study

• Symptoms and/or signs of infection, particularly (present or past) endocarditis, osteomyelitis, past tuberculosis with requirement for therapy

• Any history of hepatic or neoplastic disease

• Any history of renal disease (except diabetes)

• Abnormal liver function tests and /or NMR of liver

• Hemoglobinopathy

• History of any illness that, in the opinion of the investigator, might confound the results of the study or pose additional risks to the patient

• Pregnancy or use of inadequate contraception by female patients of childbearing potential

• Use of illicit drugs or overconsumption of alcohol (> 3 beers/day) or history of drug or alcohol abuse

• Being legally incapacitated, having significant emotional problems at the time of the study, or having a history of psychiatric disorders

• Having received antidepressant medications during the last 6 months

• Having participated the last 12 months or participating in another clinical study