Ignite Creation Date:
2024-05-05 @ 11:31 PM
Last Modification Date:
2024-10-26 @ 10:35 AM
Study NCT ID:
NCT01353833
Status:
COMPLETED
Last Update Posted:
2012-04-23
First Post:
2011-05-12
Brief Title:
Dose-effect Relationship of Low-dose IL-2 in Type 1 Diabetes
Sponsor:
Assistance Publique - Hôpitaux de Paris
Organization:
Assistance Publique - Hôpitaux de Paris
Study Overview
Official Title:
Dose-effect Relationship of Repeated Administration of Low-dose IL-2 Versus Placebo on the Kinetic of Regulatory T Cells in Patients With Type 1 Diabetes
Status:
COMPLETED
Status Verified Date:
2011-05
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
DF-IL2
Brief Summary:
IL-2 is an inducer of regulatory T cells Treg a population of lymphocytes that fail to control the autoimmune destruction of beta-cells in patients with Type 1 Diabetes T1D The investigators recently showed that low dose IL-2 is well tolerated in patients with an autoimmune disease The investigators aim to use IL-2 to inducestimulate Treg in T1D patients This study will investigate the dose effect relationship of low dose IL-2 for Treg induction such as to optimize the risk benefit ratio for this treatment in T1D By Treg induction the investigators aim to protect the remainingregenerating β-cells from autoimmune destruction thus improving or even curing T1D
Detailed Description:
Rationale
Type 1 diabetes T1D results from an autoimmune destruction of beta-pancreatic cells that regulatory T cells Treg fail to control This is in part due to a deficit in production of or response to interleukin 2 IL-2 This cytokine is essential to Treg development survival and function Importantly while IL-2 also contributes to the activation of effector T cells Teff IL-2IL-2 receptor signal transduction threshold is much lower for Treg than Teff Thus low-dose IL-2 could be a specific Treg inducerstimulator
The investigators then recently showed that low-dose IL-2 could cure recent onset diabetes in NOD mice that develop spontaneous diabetes considered as the best model of human T1D A 5-day treatment with IL-2 could cure over 30 of the mice versus 0 for controls
With these premises the investigators propose to explore if Treg induction could be obtained in patients who may have a deficit in production of or response to IL-2 Defining the dose effect relationship of low dose IL-2 for Treg induction will optimize the risk benefit ratio for IL-2 in T1D
Principal objective
To define the dose-effect relationship of low dose IL-2 for Treg induction in patient with recent onset diabetes
Evaluation Criteria
Efficacy Kinetic variation of Treg proportions within CD4 T cells in peripheral blood from Day0 to Day60
Tolerance Evaluation by clinical exams laboratory tests and monitoring of side effects The criterion for terminating the study will be the occurrence of one serious unexpected side effect in the month following IL-2 first administration in at least 2 patients
Study plan
After inclusion Day0 the patient receives a 5-day course of IL-2 or placebo Patients are randomized in 4 arms receiving either a placebo or IL-2 doses of 033 - 1 or 3 millions UIday Laboratory follow-up of peripheral blood T cell subsets will be performed at D0 to D6 daily D15 D22 and D60 by immunophenotyping and transcriptomics
Tolerance will be evaluated at D0-6 D15 D22 and D60
Methodology
Double blind placebo controlled randomized study with 4 parallel groups Patients will have T1D of autoimmune origin attested by the presence of auto-antibodies at least one of anti-islet anti-GAD anti-IA2 or anti-ZnT8 with a diagnostic inferior or equal to 24 months
Study length
Study length 9 months Patient participation 2 months Inclusion period 6 months
Type 1 diabetes T1D results from an autoimmune destruction of beta-pancreatic cells that regulatory T cells Treg fail to control This is in part due to a deficit in production of or response to interleukin 2 IL-2 This cytokine is essential to Treg development survival and function Importantly while IL-2 also contributes to the activation of effector T cells Teff IL-2IL-2 receptor signal transduction threshold is much lower for Treg than Teff Thus low-dose IL-2 could be a specific Treg inducerstimulator
The investigators then recently showed that low-dose IL-2 could cure recent onset diabetes in NOD mice that develop spontaneous diabetes considered as the best model of human T1D A 5-day treatment with IL-2 could cure over 30 of the mice versus 0 for controls
With these premises the investigators propose to explore if Treg induction could be obtained in patients who may have a deficit in production of or response to IL-2 Defining the dose effect relationship of low dose IL-2 for Treg induction will optimize the risk benefit ratio for IL-2 in T1D
Principal objective
To define the dose-effect relationship of low dose IL-2 for Treg induction in patient with recent onset diabetes
Evaluation Criteria
Efficacy Kinetic variation of Treg proportions within CD4 T cells in peripheral blood from Day0 to Day60
Tolerance Evaluation by clinical exams laboratory tests and monitoring of side effects The criterion for terminating the study will be the occurrence of one serious unexpected side effect in the month following IL-2 first administration in at least 2 patients
Study plan
After inclusion Day0 the patient receives a 5-day course of IL-2 or placebo Patients are randomized in 4 arms receiving either a placebo or IL-2 doses of 033 - 1 or 3 millions UIday Laboratory follow-up of peripheral blood T cell subsets will be performed at D0 to D6 daily D15 D22 and D60 by immunophenotyping and transcriptomics
Tolerance will be evaluated at D0-6 D15 D22 and D60
Methodology
Double blind placebo controlled randomized study with 4 parallel groups Patients will have T1D of autoimmune origin attested by the presence of auto-antibodies at least one of anti-islet anti-GAD anti-IA2 or anti-ZnT8 with a diagnostic inferior or equal to 24 months
Study length
Study length 9 months Patient participation 2 months Inclusion period 6 months
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 2010-024499-24 | EUDRACT_NUMBER | None | None |