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NCT Number: NCT01827735

Regulatory T Cells in Type 1 Diabetes Patients Treated With IL-2

Type 1 diabetes is the most common severe chronic autoimmune disease worldwide and is caused by the autoimmune (loss of self tolerance) mediated destruction of the insulin producing pancreatic beta cells thus leading to insulin deficiency and development of hyperglycaemia. Currently, medical management of type 1 diabetes focuses on intensive insulin replacement therapy to limit complications (retinopathy, nephropathy, neuropathy); nevertheless clinical outcomes remain sub optimal. There are intensive efforts to design novel immunotherapies that can arrest the autoimmune process and thereby preserve residual insulin production leading to fewer complications and better clinical outcomes.

The vast majority of genes that contribute to susceptibility to type 1 diabetes have been found to encode proteins involved in immune regulation and function. In particular, several susceptibility proteins are involved in the interleukin 2 (IL-2) pathway that regulates T cell activation and tolerance to self antigens. Aldesleukin is a human recombinant IL-2 product produced by recombinant DNA technology using genetically engineered E. coli stain containing an analog of the human interleukin-2 gene. There is substantial nonclinical, preclinical and clinical data that ultra low dose IL-2 (aldesleukin) therapy can arrest the autoimmune mediated destruction of pancreatic beta cells by induction of functional T regulatory cells. However, prior to embarking on large proof of concept trials in type 1 diabetes it is essential that the optimum dose of IL-2 (aldesleukin) is determined. The objective of this study is to establish in patients with type 1 diabetes the optimal dose of IL-2 (aldesleukin) to administer in order to increase T regulatory cell response.

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Key information

Conditions

Type 1 Diabetes Autoimmune Diseases Diabetes Mellitus Diabetes Mellitus, Type 1 Endocrine System Diseases Glucose Metabolism Disorders Immune System Diseases Metabolic Diseases Nutritional and Metabolic Diseases

Age range

18 year–50 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1 / Phase 2

Primary location

Wellcome Trust Clinical Research Facility, Addenbrooke's Hospital

Cambridge, CB2 0QQ, United Kingdom

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Written informed consent
  • Type 1 diabetes
  • 18-50 years
  • Duration of diabetes less than 24 months from diagnosis
  • One positive autoantibody (anti-islet cell, anti-GAD, anti-IA2, anti-ZnT8)

Exclusion criteria

  • Hypersensitivity to aldesleukin or any of the excipients
  • History of severe cardiac disease
  • History of malignancy within the past 5 years (with the exception of localized carcinoma of the skin that had been resected for cure or cervical carcinoma in situ)
  • History or concurrent use of immunosuppressive agents or steroids
  • History of unstable diabetes with recurrent hypoglycaemia
  • Active autoimmune, hyper or hypothyroidism
  • Active clinical infection
  • Major pre-existing organ dysfunction or previous organ allograft
  • Females who are pregnant, lactating or intend to get pregnant during the study - Males who intend to father a pregnancy during the study
  • Donation of more than 500 ml of blood within 2 months prior to aldesleukin administration
  • Participation in a previous therapeutic clinical trial within 2 months prior to aldesleukin administration
  • Abnormal ECG Abnormal full blood count, chronic renal failure (Stage 3,4,5) and/or evidence impaired liver function
  • Positive Hepatitis B surface Antigen (HBsAg) or Hepatitis C serology or Human Immunodeficiency Virus (HIV) test
  • Any medical history or clinically relevant abnormality that is deemed by the principal investigator and/or medical monitor to make the patient ineligible for inclusion because of a safety concern

Treatment and study plan

Aldesleukin (Proleukin)

Drug

A single, subcutaneous dose will be given administered with the maximum dose allowed 1.5 X 106 IU/M2.

Primary outcomes

  1. The primary endpoint is based upon the percentage of CD4+T regulatory (defined as CD3+CD4+CD25highCD127low) cells within the CD3+CD4+T cell gate following treatment with IL-2.

    Time frame: From Day 0 to Day 60

    Fluorescence-activated cell sorting assay

Secondary outcomes

  1. T regulatory cell phenotype and stability

    Time frame: From Day 0 to Day 60

    Fluorescence-activated cell sorting assay

  2. T effector cell number and phenotype

    Time frame: From Day 0 - Day 60

    Fluorescence-activated cell sorting assay

  3. T cell subset proliferation and populations

    Time frame: From Day 0 - Day 60

    Fluorescence-activated cell sorting assay

  4. Intracellular T cell and natural killer(NK) cell signalling

    Time frame: From Day 0 - Day 60

    Fluorescence-activated cell sorting assay

  5. T regulatory cell function

    Time frame: From Day 0 - Day 60

    T suppression assay

  6. IL-2 pathway genotype

    Time frame: From Day 0 - Day 60

    DNA sequencing

  7. Lymphocyte Subsets

    Time frame: From Day 0 to Day 60

    Complete blood count

  8. Serum Cytokines

    Time frame: From Day 0 to Day 60

    Enzyme-linked immuno sorbent assay

  9. Glycaemic control

    Time frame: From Day 0 to Day 60

    Self monitoring blood glucose readings, HbA1c, insulin usage

  10. Number of Participants with Adverse Events as a Measure of Safety and Tolerability

    Time frame: From Day O to Day 60

Sponsors and collaborators

Lead sponsor

Cambridge University Hospitals NHS Foundation Trust

Other

Collaborators

  • Juvenile Diabetes Research Foundation
  • National Institute for Health Research, United Kingdom
  • University of Cambridge
  • Wellcome Trust

Registry information

Official study title

Adaptive Study of IL-2 Dose on Regulatory T Cells in Type 1 Diabetes (DILT1D)

Acronym: DILT1D

Important dates

Study start
2013
Primary completion
2014
Study completion
2014
First posted
Apr 10, 2013
Registry last updated
Jun 23, 2015

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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