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Islet Allotransplantation With Steroid Free Immunosuppression

This study has been completed.
Sponsor:
Collaborator:
Institut National de la Santé Et de la Recherche Médicale, France
Information provided by (Responsible Party):
University Hospital, Lille
ClinicalTrials.gov Identifier:
NCT00446264
First received: March 9, 2007
Last updated: April 23, 2012
Last verified: February 2009
History of Changes
  Purpose

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.


Condition Intervention Phase
Type 1 Diabetes
Hypoglycemia
Metabolic Diseases
 Procedure: islet transplantation
Drug: daclizumab - sirolimus - tacrolimus
 Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Sequential Islet Transplantation With Steroid Free Immunosuppression for Type 1 Diabetes

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by University Hospital, Lille:

Primary Outcome Measures:
  • Composite Criteria: Insulin Independence and Glycosylated Hemoglobin (HbA1c) Under 6.5% at One Year [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    The percentage of insulin independents subjects with an HbA1c less than 6.5% at one year after last transplant


Secondary Outcome Measures:
  • Hypoglycemic Events [ Time Frame: day 0 to day 365 ] [ Designated as safety issue: Yes ]
    Percentage of subjects free of severe hypoglycemic events from day 0 to day 365 with the day of transplant designated day 0

  • Plasma C-peptide [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    Level of plasma C-peptide at 1 year after the first transplant

  • HbA1c < 6.5% [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    The percentage of subjects with HbA1c < 6.5% at 1 year after the first transplant

  • Percentage of Time Spent in Hypoglycemia (<0.70 mg/L) [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    percentage of time spent in hypoglycemia derived from CGMS (Continuous Glucose Monitoring System)

  • Number of Adverse Events [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
    The number of adverse events related to the procedure and to the immunosuppression


Enrollment: 14
Study Start Date: May 2003
Study Completion Date: February 2009
Primary Completion Date: October 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: islet transplantation
Each participant received up to three sequential fresh islet infusions within three months.
 Procedure: islet transplantation
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.
Other Names:
  • surgical catheterisation
  • percutaneous catheterisation
Drug: daclizumab - sirolimus - tacrolimus
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
Other Names:
  • Prograf
  • Rapamune
  • Zenapax

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • type 1 diabetes documented for more than 5 years
  • arginine stimulated C-peptide lower than 0.2 ng/mL
  • one of the following:hypoglycemia unawareness OR metabolic lability documented by one or more severe hypoglycemias or two or more hospital admissions for ketoacidosis within the previous year.

Exclusion Criteria:

  • body mass index greater than 28 kg/m2
  • non stable arteriopathy or heart disease
  • active infection
  • previous transplantation
  • hyperimmunization
  • insulin daily needs above 1.2 U/Kg
  • creatinine clearance below 60 ml/mn or urinary albumin excretion above 300 mg/d
  • malignancy
  • smoking
  • desire for pregnancy
  • psychiatric disorders
  • lack of compliance
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00446264

Locations
France
University Hospital of Lille
Lille, France, 59037
Sponsors and Collaborators
University Hospital, Lille
Institut National de la Santé Et de la Recherche Médicale, France
Investigators
Principal Investigator: Francois Pattou, MD University Hospital, Lille
Principal Investigator: Marie-Christine Vantyghem, MD PhD University Hospital, Lille
Principal Investigator: Julie Kerr-Conte, PhD Université de Lille 2
  More Information

No publications provided

Responsible Party: University Hospital, Lille
ClinicalTrials.gov Identifier: NCT00446264     History of Changes
Other Study ID Numbers: CP 01/48, PHRC, AFSSAPS 030209
Study First Received: March 9, 2007
Results First Received: May 18, 2009
Last Updated: April 23, 2012
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

Keywords provided by University Hospital, Lille:
diabetes
hypoglycemia

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 1
Hypoglycemia
Metabolic Diseases
Glucose Metabolism Disorders
Endocrine System Diseases
Autoimmune Diseases
Immune System Diseases
Sirolimus
Everolimus
Tacrolimus
 Daclizumab
Antibiotics, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Antifungal Agents
Anti-Infective Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Anti-Bacterial Agents

ClinicalTrials.gov processed this record on May 16, 2013