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Type 1 DiabetesPhase 2NCT00446264

Islet Allotransplantation With Steroid Free Immunosuppression

A Phase 2 study testing islet transplantation and daclizumab - sirolimus - tacrolimus in people with Type 1 Diabetes and Hypoglycemia, run by University Hospital, Lille at 1 site in France.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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). Read more about this study

Who is it for?
Ages 18 to 65 years
Conditions the study is for
Type 1 Diabetes, Hypoglycemia, Metabolic Diseases
What is being tested?
islet transplantation and daclizumab - sirolimus - tacrolimus
Could I receive a placebo?
No, everyone receives an active treatment
How many people
14 participants
Where
1 siteFrance
Study dates
May 2003to Feb 2009
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 65 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.

Who cannot join

  • 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
Show all 12Show fewer
  • creatinine clearance below 60 ml/mn or urinary albumin excretion above 300 mg/d
  • malignancy
  • smoking
  • desire for pregnancy
  • psychiatric disorders
  • lack of compliance

Trial locations and contacts

1 site in 1 country.

France1 site

  • University Hospital of Lille

    Lille, 59037

Other trials in France

About this study

Official title: 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.

Read the 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.

Being tested
islet transplantation, daclizumab - sirolimus - tacrolimus
Keywords
diabetes, hypoglycemia
Medical subject headings
Diabetes Mellitus, Type 1, Hypoglycemia, Metabolic Diseases, Diabetes Mellitus

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • islet transplantationProcedure or surgery

    Also called surgical catheterisation, percutaneous catheterisation

    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.

  • daclizumab - sirolimus - tacrolimusDrug

    Also called Prograf, Rapamune, Zenapax

    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

Study groups in NCT00446264
Study groupRoleWhat they receive
islet transplantationExperimentalEach participant received up to three sequential fresh islet infusions within three months.
Receives: Procedure: islet transplantation; Drug: daclizumab - sirolimus - tacrolimus

What is being measured

The primary outcome is the main question the study is designed to answer.

  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

    Measured: 1 year

Secondary outcomes (5)

  1. Hypoglycemic Events

    Percentage of subjects free of severe hypoglycemic events from day 0 to day 365 with the day of transplant designated day 0

    Measured: day 0 to day 365

  2. Plasma C-peptide

    Level of plasma C-peptide at 1 year after the first transplant

    Measured: 1 year

  3. HbA1c < 6.5%

    The percentage of subjects with HbA1c < 6.5% at 1 year after the first transplant

    Measured: 1 year

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

    percentage of time spent in hypoglycemia derived from CGMS (Continuous Glucose Monitoring System)

    Measured: 1 year

  5. Number of Adverse Events

    The number of adverse events related to the procedure and to the immunosuppression

    Measured: 1 year

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted12 Mar 2007 (estimated)
  2. Study startMay 2003
  3. Primary completionOct 2007
  4. Study completionFeb 2009

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
14 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00446264
Sponsor's protocol ID
CP 01/48
Other IDs
PHRC, AFSSAPS 030209
Status last verified
Feb 2009
First submitted
9 Mar 2007
Last updated
27 Apr 2012
Data monitoring committee
Yes

Publications

  • 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.

    PubMed 31615852

  • 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.

    PubMed 28941330

  • 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.

    PubMed 25393157

  • 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.

    PubMed 22996144

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing islet transplantation and daclizumab - sirolimus - tacrolimus in people with Type 1 Diabetes and Hypoglycemia, run by University Hospital, Lille at 1 site in France.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 3 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 27 Apr 2012. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 12 May 2010). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Composite Criteria: Insulin Independence and Glycosylated Hemoglobin (HbA1c) Under 6.5% at One Year (time frame: 1 year). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00446264, which also lists 4 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Apr 2012.

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