Clinical trial NCT01974674: Allogeneic Islet Transplantation for the Treatment of Type 1 Diabetes
Official title: Allogeneic Islet Transplantation for the Treatment of Type 1 Diabetes
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Patients With Type 1 Diabetes
Keywords: diabetes
transplantation
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
First posted: 2013-11-01
Enrollment: 19
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: restoration of normal glycemic control without insulin
timeFrame: 6 months after graft
Secondary outcomes:
measure: Restoration of normal glycemic control without insulin for a year
timeFrame: 1 year
measure: Obtaining an improvement in glycemic control
timeFrame: within 2 years after inclusion
measure: Obtaining a remission of diabetes
timeFrame: within 2 years after inclusion
measure: Improved metabolic profile determined by the OGTT and hyperglycemic clamp
timeFrame: within 2 years after inclusion
measure: Decreased glycemic variability
timeFrame: within 2 years after inclusion
measure: Reduction of oxidative stress assessed by the urinary excretion of 24 hours of 8-iso-PGF2 rates.
timeFrame: within 2 years after inclusion
measure: Decrease in the frequency, severity or poor perception of hypoglycaemia defined Hypo score
timeFrame: within the 2 years after inclusion
measure: quality of life
timeFrame: within 2 years after inclusion
measure: term graft survival
timeFrame: within 2 years of inclusion
measure: beta-cell function
timeFrame: 2 years
measure: potential of each infusion of islets
timeFrame: within 2 years after inclusion
measure: degenerative complications of diabetes
timeFrame: 2 years
Other outcomes:
Locations:
city: Paris
country: France
facility: Saint Louis hospital
state: Ile de France
Study officials:
References: