Clinical trial NCT01123187: Islet Cell Transplantation in Patients With Type I Diabetes With Previous Kidney Transplantation
Official title: Phase 2 Study of Islet Cell Transplantation in Patients With Type I Diabetes With Previous Kidney Transplantation With Steroid Free Immunosuppression
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Type 1 Diabetes
Organ Transplantation
Immunosuppression
Keywords: diabetes type 1
kidney transplantation
islet
hypoglycemia
Lead sponsor: University Hospital, Lille
Sponsor class: OTHER
Collaborators: name: Institut National de la Santé Et de la Recherche Médicale, France
First posted: 2010-05-14
Enrollment: 14
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Islet transplantation
Primary purpose: TREATMENT

Brief summary: 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.

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 \< 8% 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 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).

Primary outcomes:
measure: Composite criteria: insulin independence and Glycosylated Hemoglobin (HbA1c) under 8% at one year after the transplantation
timeFrame: One year
Secondary outcomes:
measure: The number of adverse events
timeFrame: 1 year
measure: Number of severe episodes of hypoglycemia
timeFrame: 1 year
measure: Evaluation of Diabetes complications
timeFrame: 1 year
measure: Lipid metabolism
timeFrame: 1 year
measure: Evaluation of kidney function
timeFrame: 1 year
Other outcomes:
Locations:
city: Lille
country: France
facility: University Hospital of Lille
state: Nord
Study officials:
affiliation: University Hospital, Lille
name: François PATTOU, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: University Hospital, Lille
name: Marie-Christine VANTYGHEM, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University Hospital, Lille
name: Christian NOEL, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Université de Lille 2
name: Julie KERR-CONTE, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.