NCT00446264

Brief Summary

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
14

participants targeted

Target at below P25 for phase_2

Timeline
Completed

Started May 2003

Longer than P75 for phase_2

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

May 1, 2003

Completed
3.9 years until next milestone

First Submitted

Initial submission to the registry

March 9, 2007

Completed
3 days until next milestone

First Posted

Study publicly available on registry

March 12, 2007

Completed
7 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

October 1, 2007

Completed
1.3 years until next milestone

Study Completion

Last participant's last visit for all outcomes

February 1, 2009

Completed
1.3 years until next milestone

Results Posted

Study results publicly available

May 12, 2010

Completed
Last Updated

April 27, 2012

Status Verified

February 1, 2009

Enrollment Period

4.4 years

First QC Date

March 9, 2007

Results QC Date

May 18, 2009

Last Update Submit

April 23, 2012

Conditions

Type 1 DiabetesHypoglycemiaMetabolic Diseases

Keywords

diabeteshypoglycemia

Outcome Measures

Primary Outcomes (1)

  • 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

    1 year

Secondary Outcomes (5)

  • Hypoglycemic Events

    day 0 to day 365

  • Plasma C-peptide

    1 year

  • HbA1c < 6.5%

    1 year

  • Percentage of Time Spent in Hypoglycemia (<0.70 mg/L)

    1 year

  • Number of Adverse Events

    1 year

Study Arms (1)

islet transplantation

EXPERIMENTAL

Each participant received up to three sequential fresh islet infusions within three months.

Procedure: islet transplantationDrug: daclizumab - sirolimus - tacrolimus

Interventions

islet transplantationPROCEDURE

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
islet transplantation
daclizumab - sirolimus - tacrolimusDRUG

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
islet transplantation

Eligibility Criteria

Age18 Years - 65 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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.

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

University Hospital of Lille

Lille, 59037, France

Location

Related Publications (4)

  • Vantyghem MC, Chetboun M, Gmyr V, Jannin A, Espiard S, Le Mapihan K, Raverdy V, Delalleau N, Machuron F, Hubert T, Frimat M, Van Belle E, Hazzan M, Pigny P, Noel C, Caiazzo R, Kerr-Conte J, Pattou F; Members of the Spanish Back Pain Research Network Task Force for the Improvement of Inter-Disciplinary Management of Spinal Metastasis. Ten-Year Outcome of Islet Alone or Islet After Kidney Transplantation in Type 1 Diabetes: A Prospective Parallel-Arm Cohort Study. Diabetes Care. 2019 Nov;42(11):2042-2049. doi: 10.2337/dc19-0401.

    PMID: 31615852DERIVED

  • Benomar K, Chetboun M, Espiard S, Jannin A, Le Mapihan K, Gmyr V, Caiazzo R, Torres F, Raverdy V, Bonner C, D'Herbomez M, Pigny P, Noel C, Kerr-Conte J, Pattou F, Vantyghem MC. Purity of islet preparations and 5-year metabolic outcome of allogenic islet transplantation. Am J Transplant. 2018 Apr;18(4):945-951. doi: 10.1111/ajt.14514. Epub 2017 Nov 11.

    PMID: 28941330DERIVED

  • Caiazzo R, Vantyghem MC, Raverdi V, Bonner C, Gmyr V, Defrance F, Leroy C, Sergent G, Hubert T, Ernst O, Noel C, Kerr-Conte J, Pattou F. Impact of Procedure-Related Complications on Long-term Islet Transplantation Outcome. Transplantation. 2015 May;99(5):979-84. doi: 10.1097/TP.0000000000000458.

    PMID: 25393157DERIVED

  • Vantyghem MC, Raverdy V, Balavoine AS, Defrance F, Caiazzo R, Arnalsteen L, Gmyr V, Hazzan M, Noel C, Kerr-Conte J, Pattou F. Continuous glucose monitoring after islet transplantation in type 1 diabetes: an excellent graft function (beta-score greater than 7) Is required to abrogate hyperglycemia, whereas a minimal function is necessary to suppress severe hypoglycemia (beta-score greater than 3). J Clin Endocrinol Metab. 2012 Nov;97(11):E2078-83. doi: 10.1210/jc.2012-2115. Epub 2012 Sep 20.

    PMID: 22996144DERIVED

MeSH Terms

Conditions

Diabetes Mellitus, Type 1HypoglycemiaMetabolic DiseasesDiabetes Mellitus

Interventions

Islets of Langerhans TransplantationTacrolimusSirolimusDaclizumab

Condition Hierarchy (Ancestors)

Glucose Metabolism DisordersNutritional and Metabolic DiseasesEndocrine System DiseasesAutoimmune DiseasesImmune System Diseases

Intervention Hierarchy (Ancestors)

Cell TransplantationCell- and Tissue-Based TherapyBiological TherapyTherapeuticsEndocrine Surgical ProceduresSurgical Procedures, OperativeTransplantationMacrolidesLactonesOrganic ChemicalsAntibodies, Monoclonal, HumanizedAntibodies, MonoclonalAntibodiesImmunoglobulinsImmunoproteinsBlood ProteinsProteinsAmino Acids, Peptides, and ProteinsSerum GlobulinsGlobulins

Results Point of Contact

Title
Violeta Raverdy
Organization
University of Lille
vraverdi@univ-lille2.fr
00 33 3 20 62 34 30

Study Officials

  • 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

    PRINCIPAL INVESTIGATOR

Publication Agreements

PI is Sponsor Employee
Yes
Restrictive Agreement
No

Study Design

Study Type
interventional
Phase
phase 2
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

March 9, 2007

First Posted

March 12, 2007

Study Start

May 1, 2003

Primary Completion

October 1, 2007

Study Completion

February 1, 2009

Last Updated

April 27, 2012

Results First Posted

May 12, 2010

Record last verified: 2009-02

Locations

FR(1)