Islet Cell Transplantation in Patients With Type I Diabetes With Previous Kidney Transplantation

This study is currently recruiting participants. (see Contacts and Locations)
Verified February 2009 by University Hospital, Lille
Sponsor:
Collaborator:
Institut National de la Santé Et de la Recherche Médicale, France
Information provided by (Responsible Party):
University Hospital, Lille
ClinicalTrials.gov Identifier:
NCT01123187
First received: May 11, 2010
Last updated: August 31, 2012
Last verified: February 2009
  Purpose

This single center phase 2 clinical trial, is designed for confirming the efficacy and safety of sequential islet allotransplantation with steroid free immunosuppression in patients with previous kidney transplantation.


Condition Intervention Phase
Type 1 Diabetes
Organ Transplantation
Immunosuppression
Procedure: islet transplantation
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase 2 Study of Islet Cell Transplantation in Patients With Type I Diabetes With Previous Kidney Transplantation With Steroid Free Immunosuppression

Resource links provided by NLM:


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 after the transplantation [ Time Frame: One year ] [ Designated as safety issue: No ]
    Percent of insulin-independent patients with a Glycosylated Hemoglobin (HbA1c) under 6.5% at one year after injection of approximately 10,000 islets equivalents / kg (IE/kg).


Secondary Outcome Measures:
  • The 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

  • Number of severe episodes of hypoglycemia [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
    Number of severe episodes of hypoglycemia (requiring the use of third)

  • Evaluation of Diabetes complications [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
    Evaluation of Diabetes complications: retinopathy, neuropathy, nephropathy

  • Lipid metabolism [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    Lipid metabolism assessed by measurement of total cholesterol and HDL cholesterol, triglycerides, ApoA1, apoB, apoE, free fatty acids and lipid.

  • Evaluation of kidney function [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
    Evaluation of kidney function (creatinine, creatinine clearance,proteinurie)


Estimated Enrollment: 19
Study Start Date: March 2003
Estimated Study Completion Date: March 2015
Estimated Primary Completion Date: March 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: islet transplantation 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

Detailed Description:

The beneficial effects of glycemic control on both survival and function of transplanted kidneys in patients with type 1 diabetes mellitus have been recognized.

The purpose of this study is to reverse hyperglycemia and insulin dependency, by islet cell transplantation, in patients with type 1 diabetes mellitus who have a stable kidney allograft.

The study primary efficacy endpoint is graft survival defined as insulin independence and HbA1c < 6.5% at 1 year post first transplant. Secondary outcomes are graft function and metabolic control

The immunosuppression protocol for the kidney graft was converted to sirolimus+tacrolimus regimen 6 months before islet transplantation to exclude negative effects on kidney graft function.

  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 mellitus. Documentation of negative basal and stimulated C-peptide and diagnosis of diabetes for at least 5 years.
  • Recipient of renal transplant with good function (creatinine clearance >/=60 ml/min)
  • Stable immunosuppression consisting of any combination of sirolimus, tacrolimus for at least 6 months, without major complications
  • Ability to give informed consent.
  • Age greater than or equal to 18 years or less than or equal to 65 years
  • No evidence of liver disease (liver enzymes < twice the upper limit of normal)

Exclusion Criteria:

  • Age below 18 years and above 65 years
  • Significant cardiovascular disease, including non-correctable coronary artery disease and/or recent myocardial infarction(within last 12 months); extensive peripheral vascular disease not correctable by surgery, unstable angina
  • Untreated proliferative retinopathy.
  • Recent Cerebrovascular accident (within last 12 months)
  • Recent unresolved acute infection, or chronic infection, including tuberculosis, HIV, HBV, HCV, CMV or positive skin test for TB
  • Any history of malignancy, except squamous or basal skin cancer or in situ cancer of the cervix.
  • History of non-compliance, or inability to demonstrate capacity to comply with strict blood glycemic control and insulin pump therapy.
  • Psychiatric illness that is untreated, or likely to interfere significantly with transplantation despite treatment.
  • Pregnant women, women intending future pregnancy, women of reproductive potential who are unable or unwilling to follow effective contraceptive measures for the duration of immunosuppressive therapy
  • Fasting C-peptide > 0.2 ng/ml
  • Creatinine > 25mg/l
  • Alkaline phosphatase, total bilirubin, Alanine Aminotransferase (ALT)or Aspartate Aminotransferase (AST) > twice the upper limit of normal
  • Significant liver disease (elevation of liver enzymes > twice the upper limit of normal for each of ALT and AST, liver masses including portal vein thrombosis, evidence of portal hypertension, or significant, untreated gallbladder disease (i.e., gallstones).
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01123187

Contacts
Contact: Violeta Raverdy, MD 0033 320 62 34 30 vraverdi@univ-lille2.fr
Contact: Francois Pattou, MD, Pr fpattou@univ-lille2.fr

Locations
France
University Hospital of Lille Recruiting
Lille, Nord, France, 59000
Sponsors and Collaborators
University Hospital, Lille
Institut National de la Santé Et de la Recherche Médicale, France
Investigators
Principal Investigator: François PATTOU, MD, PhD University Hospital, Lille
Principal Investigator: Marie-Christine VANTYGHEM, MD University Hospital, Lille
Principal Investigator: Christian NOEL, MD University Hospital, Lille
Principal Investigator: Julie KERR-CONTE, MD Université de Lille 2
  More Information

No publications provided

Responsible Party: University Hospital, Lille
ClinicalTrials.gov Identifier: NCT01123187     History of Changes
Other Study ID Numbers: CP 95/120, 98001, DGS 980032
Study First Received: May 11, 2010
Last Updated: August 31, 2012
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

Keywords provided by University Hospital, Lille:
diabetes type 1
kidney transplantation
islet
hypoglycemia

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 1
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Autoimmune Diseases
Immune System Diseases

ClinicalTrials.gov processed this record on August 28, 2014