Islet Allotransplantation With Steroid Free Immunosuppression

April 23, 2012 updated by: University Hospital, Lille

Sequential Islet Transplantation With Steroid Free Immunosuppression for Type 1 Diabetes

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

14

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • France
      • Lille, France, 59037
        • University Hospital of Lille

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Composite Criteria: Insulin Independence and Glycosylated Hemoglobin (HbA1c) Under 6.5% at One Year
Time Frame: 1 year
The percentage of insulin independents subjects with an HbA1c less than 6.5% at one year after last transplant
1 year

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Hypoglycemic Events
Time Frame: day 0 to day 365
Percentage of subjects free of severe hypoglycemic events from day 0 to day 365 with the day of transplant designated day 0
day 0 to day 365
Plasma C-peptide
Time Frame: 1 year
Level of plasma C-peptide at 1 year after the first transplant
1 year
HbA1c < 6.5%
Time Frame: 1 year
The percentage of subjects with HbA1c < 6.5% at 1 year after the first transplant
1 year
Percentage of Time Spent in Hypoglycemia (<0.70 mg/L)
Time Frame: 1 year
percentage of time spent in hypoglycemia derived from CGMS (Continuous Glucose Monitoring System)
1 year
Number of Adverse Events
Time Frame: 1 year
The number of adverse events related to the procedure and to the immunosuppression
1 year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University Hospital, Lille

Collaborators

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

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

May 1, 2003

Primary Completion (Actual)

October 1, 2007

Study Completion (Actual)

February 1, 2009

Study Registration Dates

First Submitted

March 9, 2007

First Submitted That Met QC Criteria

March 9, 2007

First Posted (Estimate)

March 12, 2007

Study Record Updates

Last Update Posted (Estimate)

April 27, 2012

Last Update Submitted That Met QC Criteria

April 23, 2012

Last Verified

February 1, 2009

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CP 01/48
  • PHRC (French Ministry of Health)
  • AFSSAPS 030209 (Other Identifier: AFSSAPS)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Metabolic Diseases

Clinical Trials on islet transplantation

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Iran

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe