Allogeneic Islet Transplantation for the Treatment of Type 1 Diabetes

Phase 2

• Conditions: Patients With Type 1 Diabetes

• Registration Number: NCT01974674
• Lead Sponsor: Assistance Publique - Hôpitaux de Paris

Brief Summary

It is a multicentre, sequential, phase II clinical trial, aiming at evaluating the allogeneic islet transplantation for the treatment of type 1 diabetes.

19 patients with type 1 diabetes will be included and ideally distributed evenly: patients with unstable diabetes without renal insufficiency (AI group for "islet alone" by the international customary determination) and patients with a functioning kidney transplant (IAK group for "islet after kidney"). The main endpoint will be defined by the restoration of normal glycemic control without insulin at 6 months after graft.

Detailed Description

Not available

Study Timeline

• Study Start: 2013-07
• Study First Submitted: 2013-10-28
• Study First Submitted QC: 2013-10-31
• Study First Posted: 2013-11-01
• Status Verified: 2016-09
• Last Update Submitted: 2016-09-28
• Last Update Posted: 2016-09-29
• Primary Completion: 2016-12
• Study Completion: 2022-01

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 19

Inclusion Criteria

• Patients with type 1 diabetes
• 18 <Age <55 years
• Plasma C-peptide <0.2 ng/ml basal and stimulated glucagon
• Evolution of diabetes for more than 5 years
• Regular patient follow-up (> or equal to 2 visits per year from the same diabetologist)
• Patient who received the information and have given their consent in writing
• Absence of HIV, hepatitis B and hepatitis C, HTLV-1-2
• ABO compatibility with the donor
• Cross match negative
• Anti-HLA antibodies (class I and / or class II) detected by lymphocytotoxicity <20%
• PCR negative for the BK virus in the blood (so as not to amplify the BK virus replication with the ATG).
• Accepting patients effective contraception during the study period

For patients in group IA

• Glomerular filtration rate estimated by the MDRD> 50 ml/min/1.73m2

• No perception of hypoglycaemia (less than 0.54 mg/dl glucose) at least one value documented in the two years preceding and/or

• Occurrence of at least one severe hypoglycemic episode (with a third required) and unexplained in the two years before and/or at least two episodes of ketoacidosis per year

• Average HbA1c> 8.5% over two years, despite intensified treatment (basal pattern, bolus)

  • For patients in the IAK

• functional renal graft for at least 1 year

• glomerular filtration rate> 50 ml/min/1.73 m2

• proteinuria <0.5 g/day

• Absence of acute rejection in renal previous 6 months

Exclusion Criteria

• BMI > 28
• Need insulin > 1 U/kg per day
• Pregnancy, lactation
• Intention of childbearing for the two sexes
• Psychiatric Disorders
• Inability to communicate or cooperate with the investigator
• Lack of therapeutic compliance, including HbA1C > 12%
• Chronic liver disease
• Progressive heart disease myocardial infarction within 6 months prior to inclusion, unbalanced CHD)
• Proliferative retinopathy unstabilized
• History of cancer, whatever the date, except for basal or squamous cell skin cancers over 1 year.
• Systemic infection
• Chronic high risk of requiring corticosteroids
• Need for long-term corticosteroid, outside that specified in renal transplantation, the patients will be weaned before transplantation
• Anticoagulant vitamin K or antiplatelet treatments
• Disorders of hemostasis TP <60 % TCA > 1.5 times the control
• Anti-HLA antibodies ( class I and/or class II ) detected by lymphocytotoxicity > 20%
• Platelets < 100 giga/L and/or neutrophils <1.5 giga/L
• Chronic intoxication by alcohol, tobacco, or other substance (abstinence > 6 months required)
• Active infection by hepatitis B, hepatitis C and HIV, HTLV-1-HTLV2
• Ascites

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Primary Outcome Measures

Name	Time	Method
restoration of normal glycemic control without insulin	6 months after graft	the restoration of normal glycemic control without insulin therapy will be evaluated by measuring; - A fasting glucose (\> 8 hours) less than 1.25 g/L and a 2 hours glucose after oral intake of 75g of glucose, less than 2 g/L in a patient without insulin for at least 15 consecutive days during the the first 6 months from day 0.

Secondary Outcome Measures

Name	Time	Method
potential of each infusion of islets	within 2 years after inclusion	number of IEQ/kg of recipient required to reduce the daily insulin dose of 1 unit
Obtaining a remission of diabetes	within 2 years after inclusion	The remission of diabetes is defined by the normality of blood glucose or insulin without lHbA1c.; The normality of blood glucose is defined below 1.20 g/L and postprandial fasting glycemia less than 1.60 g/L in the book self-monitoring (including 6/7 blood glucoses during the previous 3 days evaluation visit).; Normal HbA1c is defined as less than 6.5%.
Decrease in the frequency, severity or poor perception of hypoglycaemia defined Hypo score	within the 2 years after inclusion
Restoration of normal glycemic control without insulin for a year	1 year
Obtaining an improvement in glycemic control	within 2 years after inclusion	HbA1c \<6.5%, with lower insulin doses by 30%
quality of life	within 2 years after inclusion	defined by questionnaires DQOL and SF-36
beta-cell function	2 years	based on beta-score
Improved metabolic profile determined by the OGTT and hyperglycemic clamp	within 2 years after inclusion
Reduction of oxidative stress assessed by the urinary excretion of 24 hours of 8-iso-PGF2 rates.	within 2 years after inclusion
degenerative complications of diabetes	2 years
Decreased glycemic variability	within 2 years after inclusion	defined on blood glucose and / or glucose holter
term graft survival	within 2 years of inclusion	defined by the rate of C-peptide

Trial Locations

Locations (1)

Saint Louis hospital; 🇫🇷 Paris, Ile de France, France