A Phase 2 interventional study of islet transplantation and daclizumab - sirolimus - tacrolimus in Type 1 Diabetes, Hypoglycemia and Metabolic Diseases, sponsored by University Hospital, Lille. Completed at 1 site in France. Open to participants aged 18 Years to 65 Years. Per ClinicalTrials.gov, last updated 2012-04-27.
Sponsored by University Hospital, Lille · Phase 2, Interventional, and Treatment
The restoration of endogenous insulin secretion carries significant hopes for shifting the paradigm of life long exogenous insulin therapy in selected groups of patients with type 1 diabetes(T1D). After decades of frustrating clinical attempts, the Edmonton group set up in 2000 new standards for islet transplantation in patients with brittle T1D by achieving insulin independence in 80 percent of patients. These seminal results have however proved much more difficult to duplicate than initially expected.
This single center phase 2 clinical trial, duplicating the Edmonton protocol, is designed for confirming the consistent short term efficacy and safety of sequential islet allotransplantation with steroid free immunosuppression in patients with severe T1D.
The short term effectiveness of islet transplantation for alleviating hypoglycemia and controlling glucose homeostasis while limiting or even avoiding the nedd for exogenous insulin has been established despite protocol modifications in donor selection, islet preparation or recipient treatment, insulin independence with adequate metabolic control was however rarely prolonged beyond two years. The most frequently proposed explanations include chronic allogenic rejection, recurrence of autoimmunity and beta cell toxicity from administered immunosuppressive drugs.
Fourteen patients were enrolled in this single center phase 2 trial initiated in 2003. Eligible patients were males or females between 18 and 65 years of age, with type 1 diabeted documented for more than 5 years, arginine stimulated C-peptide lower than 0.2ng/ml, and hypoglycemia awareness or documented metabolic lability. Exclusion criteria included body mass index greater than 28Kg/m2, unstable arteriopathy or heart disease, active infection, previous transplantation, insulin daily requirements above 1.2 UI/kg, creatinin clearance below 60 ml/mn/m2 or urinary albumin excretion above 300 mg/day, malignancy, smoking, desire for pregnancy, psychiatric disorders and lack of compliance. The study primary efficacy endpoint was graft survival defined as insulin independence and HbA1c\<6.5%. Secondary outcomes were graft function and metabolic control.
3,522 studies on the registry are indexed under Diabetes Mellitus, Type 1; 577 are open to participants now.
This study's enrollment of 14 is below the median of 40 across 2,649 interventional studies indexed under Diabetes Mellitus, Type 1.
Browse Diabetes Mellitus, Type 1 studies →University Hospital, Lille is the lead sponsor of 625 studies on the registry; 141 are open to participants now.
Counted across the registry records on this site, refreshed daily.
Exclusion Criteria:
Each participant received up to three sequential fresh islet infusions within three months.
Procedure: islet transplantation · Drug: daclizumab - sirolimus - tacrolimus
Islet transplantation consisted of up to three sequential fresh islet infusions within three months. Access to the portal vein was gained under general anesthesia by percutaneous catheterisation of a peripheral portal branch under ultrasound guidance or by surgical catheterisation of a small mesenteric vein.
Also known as: surgical catheterisation, percutaneous catheterisation
Immunosuppressive consisted of Tacrolimus, target through level at 3-6 ng/ml, Sirolimus, target through level at 12-15 ng/ml for three months and at 7-10 ng/ml thereafter. A five-dose induction course of Daclizumab 1mg/Kg was administered biweekly beginning one hour prior to the first infusion
Also known as: Prograf, Rapamune, Zenapax
Composite Criteria: Insulin Independence and Glycosylated Hemoglobin (HbA1c) Under 6.5% at One Year
The percentage of insulin independents subjects with an HbA1c less than 6.5% at one year after last transplant
Time frame: 1 year
Hypoglycemic Events
Percentage of subjects free of severe hypoglycemic events from day 0 to day 365 with the day of transplant designated day 0
Time frame: day 0 to day 365
Plasma C-peptide
Level of plasma C-peptide at 1 year after the first transplant
Time frame: 1 year
HbA1c < 6.5%
The percentage of subjects with HbA1c \< 6.5% at 1 year after the first transplant
Time frame: 1 year
Percentage of Time Spent in Hypoglycemia (<0.70 mg/L)
percentage of time spent in hypoglycemia derived from CGMS (Continuous Glucose Monitoring System)
Time frame: 1 year
Number of Adverse Events
The number of adverse events related to the procedure and to the immunosuppression
Time frame: 1 year
Recruitment period: 2003-2006 University Lille Hospital
| Milestone | Single Arm Group |
|---|---|
| Started | 14 |
| Completed | 14 |
| Not completed | 0 |
The percentage of insulin independents subjects with an HbA1c less than 6.5% at one year after last transplant
| Percentage of patients | Single Arm Group |
|---|---|
| Composite Criteria: Insulin Independence and Glycosylated Hemoglobin (HbA1c) Under 6.5% at One Year | 71 ± 29 |
Percentage of subjects free of severe hypoglycemic events from day 0 to day 365 with the day of transplant designated day 0
| Percentage of patients | Single Arm Group |
|---|---|
| Hypoglycemic Events | 0 ± 0 |
Level of plasma C-peptide at 1 year after the first transplant
| ng/ml | Single Arm Group |
|---|---|
| Plasma C-peptide | 1.7 ± 0.9 |
The percentage of subjects with HbA1c \< 6.5% at 1 year after the first transplant
| Percentage of participants | Single Arm Group |
|---|---|
| HbA1c < 6.5% | 64.3 ± 35.7 |
percentage of time spent in hypoglycemia derived from CGMS (Continuous Glucose Monitoring System)
| percentage of time | Single Arm Group |
|---|---|
| Percentage of Time Spent in Hypoglycemia (<0.70 mg/L) | 11.37 ± 3.92 |
The number of adverse events related to the procedure and to the immunosuppression
| number events | Single Arm Group |
|---|---|
| Number of Adverse Events | 33 |
Collected over 1 year. Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Single Arm Group | — | 12/14 (85.7%) | 9/14 (64.3%) |
| Event | Single Arm Group |
|---|---|
| neutropeniaBlood and lymphatic system disorders | 4/14 |
| anemiaBlood and lymphatic system disorders | 3/14 |
| diarrheaGastrointestinal disorders | 3/14 |
| choleperitonitisHepatobiliary disorders | 1/14 |
| cholestasisGastrointestinal disorders | 1/14 |
| Increase of creatininRenal and urinary disorders | 1/14 |
| Increase of SGPTHepatobiliary disorders | 1/14 |
| Incarcerated herniaGastrointestinal disorders | 1/14 |
| InfectionInfections and infestations | 1/14 |
| hemocholecystHepatobiliary disorders | 1/14 |
| Event | Single Arm Group |
|---|---|
| oral ulcerationsSkin and subcutaneous tissue disorders | 5/14 |
| dermatosisSkin and subcutaneous tissue disorders | 4/14 |
| leg edemaSkin and subcutaneous tissue disorders | 2/14 |
| Age, Categorical(Participants) | Single Arm Group |
|---|---|
| <=18 years | 0 |
| Between 18 and 65 years | 14 |
| >=65 years | 0 |
| Age Continuous(years) | Single Arm Group |
|---|---|
| Mean | 44 ± 13 |
| Sex: Female, Male(Participants) | Single Arm Group |
|---|---|
| Female | 7 |
| Male | 7 |
| Region of Enrollment(participants) | Single Arm Group |
|---|---|
| France | 14 |
This study is completed, as verified in Feb 2009. You cannot join it, but the record below documents what was studied.
Get an email when the registry record changes — status, dates, results — or when someone posts here.
Sign in to followQuestions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.
Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.
Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.
University Hospital, Lille