Trial record 2 of 3 for:    Tregs | Diabetes

Dose Finding Study of Il-2 at Ultra-low Dose in Children With Recently Diagnosed Type 1 Diabetes (DFIL2-Child)

This study is currently recruiting participants.
Verified March 2013 by Assistance Publique - Hôpitaux de Paris
Sponsor:
Information provided by (Responsible Party):
Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier:
NCT01862120
First received: December 10, 2012
Last updated: June 27, 2013
Last verified: March 2013
  Purpose

Human recombinant interleukin-2 (rhIL-2) is a biological signalling protein playing a key role in the regulation of the immune system. At high doses, rhIL-2 activates the immune effectors T cells (TEFFS) while at low doses rhIL-2 induces and activates regulatory T cells (TREGS), a population of immune cells controlling the immune Teff response. In patients with Type 1 Diabetes (T1D), TREGS fail to control the autoimmune destruction by TEFFS of pancreatic beta-cells producing insulin. The investigator recently showed that rhIL-2 at low dose is well tolerated in patients with an autoimmune disease and in adults with established T1D, inducing TREGS without effects on TEFFS. The investigators aim to use rhIL-2 at low dose to induce/stimulate TREGS in young recently diagnosed T1D patients. This study will investigate the dose effect relationship of low dose rhIL-2 on TREG induction such as to optimize the risk benefit ratio of this treatment in T1D. Through Treg induction, the investigators aim to protect the remaining/regenerating pancreatic β-cells from autoimmune destruction, thus improving or even curing T1D.


Condition Intervention Phase
Type 1 Diabetes
Drug: Dose D1 of interleukin-2
Drug: placebo
Drug: Dose D2 of Interleukin-2
Drug: Dose D3 of interleukin-2
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Subject)
Primary Purpose: Treatment
Official Title: Induction of Regulatory T Cells for the Treatment of Recently Diagnosed Type 1 Diabetes: Dose Finding Study of the Lowest Active Dose of IL-2 in Children

Resource links provided by NLM:


Further study details as provided by Assistance Publique - Hôpitaux de Paris:

Primary Outcome Measures:
  • Treg response following the induction cure period [ Time Frame: day 22 ] [ Designated as safety issue: No ]
    expressed as % total CD4 cells


Secondary Outcome Measures:
  • Fasting plasma concentration of C-peptide [ Time Frame: Baseline ] [ Designated as safety issue: Yes ]
  • Fasting plasma concentration of C-peptide [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
  • Fasting plasma concentration of C-peptide [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
  • Fasting plasma concentration of C-peptide [ Time Frame: day 466 ] [ Designated as safety issue: Yes ]
  • C-peptide AUC response to a mixed meal tolerance test [ Time Frame: Baseline ] [ Designated as safety issue: Yes ]
  • C-peptide AUC response to a mixed meal tolerance test [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
  • C-peptide AUC response to a mixed meal tolerance test [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
  • C-peptide AUC response to a mixed meal tolerance test [ Time Frame: day 466 ] [ Designated as safety issue: Yes ]
  • IDAA1C score [ Time Frame: Baseline ] [ Designated as safety issue: Yes ]
    is a score defined as A1C (percent) + [4 x insulin dose (units per kilogram per 24 h)] without unit

  • Fasting plasma concentration of C-peptide [ Time Frame: 3 months ] [ Designated as safety issue: Yes ]
  • Fasting plasma concentration of C-peptide [ Time Frame: 9 months ] [ Designated as safety issue: Yes ]
  • HbA1c [ Time Frame: Baseline ] [ Designated as safety issue: Yes ]
  • IDAA1C score [ Time Frame: 3 months ] [ Designated as safety issue: Yes ]
    is a score defined as A1C (percent) + [4 x insulin dose (units per kilogram per 24 h)] without unit

  • IDAA1C score [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
    is a score defined as A1C (percent) + [4 x insulin dose (units per kilogram per 24 h)] without unit

  • IDAA1C score [ Time Frame: 9 months ] [ Designated as safety issue: Yes ]
    is a score defined as A1C (percent) + [4 x insulin dose (units per kilogram per 24 h)] without unit

  • IDAA1C score [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
    is a score defined as A1C (percent) + [4 x insulin dose (units per kilogram per 24 h)] without unit

  • IDAA1C score [ Time Frame: day 466 ] [ Designated as safety issue: Yes ]
    is a score defined as A1C (percent) + [4 x insulin dose (units per kilogram per 24 h)] without unit

  • HbA1c [ Time Frame: 3 months ] [ Designated as safety issue: Yes ]
  • HbA1c [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
  • HbA1c [ Time Frame: 9 months ] [ Designated as safety issue: Yes ]
  • HbA1c [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
  • HbA1c [ Time Frame: day 466 ] [ Designated as safety issue: Yes ]
  • Treg response during the maintenance period [ Time Frame: month 1 from month 12 ] [ Designated as safety issue: No ]
    Treg response expressed as the % / CD4 will be measured several times (day 29, day 57, day 113, day 115, day 127, day 197, day 281, day 351, day 365,

  • Treg response after the last administration [ Time Frame: day 379 ] [ Designated as safety issue: No ]
  • Treg response after the last administration [ Time Frame: day 466 ] [ Designated as safety issue: No ]

Estimated Enrollment: 24
Study Start Date: June 2013
Estimated Study Completion Date: December 2014
Estimated Primary Completion Date: September 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: interleukin-2
Dose D1 of interleukin-2
Drug: Dose D1 of interleukin-2
Interleukin-2 by subcutaneous injection with: Single administration at day 1, followed at day 15 by an induction treatment of 5 days once daily repeated administration, and at day 30 by a maintenance treatment with a single administration every two weeks during one year.
Other Name: IL2
Experimental: Dose D2 of interleukin-2
Dose D2 of interleukin-2
Drug: Dose D2 of Interleukin-2
Interleukin-2 by subcutaneous injection with: Single administration at day 1, followed at day 15 by an induction treatment of 5 days, and at day 30 by a maintenance treatment with a single administration every two weeks during one year.
Experimental: Dose D3 of interleukin-2
Dose D3 of interleukin-2
Drug: Dose D3 of interleukin-2
Interleukin-2 by subcutaneous injection with: Single administration at day 1, followed at day 15 by an induction treatment of 5 days, and at day 30 by a maintenance treatment with a single administration every two weeks during one year.
Other Name: Il2
Placebo Comparator: placebo
placebo
Drug: placebo
subcutaneous injection with: Single administration at day 1, followed at day 15 by an induction treatment of 5 days, and at day 30 by a maintenance treatment with a single administration every two weeks during one year.

Detailed Description:

Main objective:

Define the lowest dose of rhIL-2 inducing TREGS in children with recently diagnosed type 1 diabetes.

Conduct of the study:

Three doses will be studied versus placebo in parallel groups of six patients. Each dose or placebo will be studied according to three periods of treatment:

  1. Acute tolerance following a single administration at day 1 [day 1- day 15].
  2. Induction of TREGS following a cure of 5 days repeated once daily administration [day 15 - day 30].
  3. Maintenance of TREGS following repeated administration once every two weeks for one year [day 30 - day 360].

At each treatment period, Treg response and tolerance will be evaluated. In addition, overall response on T1D parameters will be assessed throughout the study.

  Eligibility

Ages Eligible for Study:   7 Years to 12 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion criteria :

  • Age [7-12] years;

    • With a T1D diagnosis (as ADA)
    • Treated with insulin for ≤ 3 months,
    • With at least one auto-antibody among: anti-insulin, anti-GAD, anti-IA2, anti-ZnT8 ;
  • No clinically relevant abnormal findings for haematology, biochemistry, liver and kidney functions
  • Informed consent signed by the patient, the parents, and the investigator before any intervention necessary for the trial.

Exclusion criteria :

  • Contra-indications to IL-2 :

    • Hyper sensibility to IL-2 or its excipients,
    • Severe cardiopathy
    • Previous organ allograft
    • Ongoing infection requiring antibiotherapy,
    • O2 Saturation ≤ 90 %
    • Severe impairment of any vital organ
    • Documented history of other auto-immune diseases (except for auto-antibodies for, IAA, GADA, IA-2A, anti-ZnT8A, and stable thyroiditis with normal TSH (<10 mUI/L), T3 and, T4 levels.
    • Diabetes onset characteristics including:

      • Continuous nocturnal polyuria ≥ 3 months ;
      • Inaugural acidosis (with venous Ph < 7.25) ;
      • HbA1c at diagnostic ≥ 13%;
      • Weight loss ≥ 10 % at diagnosis ;
      • Positive autoantibodies to 21-hydroxylase
      • Stage 2 obesity
  • Non authorized concomitant treatment : immuno-modulators, cytotoxic drugs, drug modifying plasma glycemia
  • vaccination ≤ 4 weeks with life vaccin
  • Positive serology (IgM) to the Epstein-Barr virus (EBV) and/or cytomegalovirus (CMV), reflecting an acute infection.
  • Participation to another clinical investigation in previous 3 months
  • No affiliation to National Health Insurance
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01862120

Contacts
Contact: David Klatzmann, MD, PhD +33(0) 1 42 17 74 61 David.klatzmann@upmc.fr

Locations
France
Service d'Endocrinologie Pédiatrique Recruiting
Le Kremlin Bicetre, France, 94275
Service de Pédiatrie - CHU de Nîmes Recruiting
Nimes, France, 30029 cedex 9
Sponsors and Collaborators
Assistance Publique - Hôpitaux de Paris
Investigators
Principal Investigator: David Klatzmann, MD, PhD APHP
  More Information

No publications provided

Responsible Party: Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier: NCT01862120     History of Changes
Other Study ID Numbers: P101106
Study First Received: December 10, 2012
Last Updated: June 27, 2013
Health Authority: France: Ministry of Health

Keywords provided by Assistance Publique - Hôpitaux de Paris:
Recently diagnosed
Regulatory T Cells
Tolerance Induction
Paediatrics
Low dose
IL-2

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 1
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Autoimmune Diseases
Immune System Diseases
Interleukin-2
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Central Nervous System Agents

ClinicalTrials.gov processed this record on April 17, 2014