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Regulatory T Cells in Type 1 Diabetes Patients Treated With IL-2 (DILT1D)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01827735
Recruitment Status : Completed
First Posted : April 10, 2013
Last Update Posted : June 23, 2015
Sponsor:
Collaborators:
University of Cambridge
Juvenile Diabetes Research Foundation
National Institute for Health Research, United Kingdom
Wellcome Trust
Information provided by (Responsible Party):
Dr Frank Waldron-Lynch, Cambridge University Hospitals NHS Foundation Trust

Study Description
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Brief Summary:

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.


Condition or disease Intervention/treatment Phase
Type 1 Diabetes Drug: Aldesleukin (Proleukin) Phase 1 Phase 2

Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 40 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
Official Title: Adaptive Study of IL-2 Dose on Regulatory T Cells in Type 1 Diabetes (DILT1D)
Study Start Date : March 2013
Actual Primary Completion Date : May 2014
Actual Study Completion Date : May 2014

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Diabetes Type 1
Drug Information available for: Aldesleukin

Arms and Interventions
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Intervention Details:
  • Drug: Aldesleukin (Proleukin)
    A single, subcutaneous dose will be given administered with the maximum dose allowed 1.5 X 106 IU/M2.

Outcome Measures
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Primary Outcome Measures :
  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 Outcome Measures :
  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 ]

Eligibility Criteria
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Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 50 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01827735


Locations
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United Kingdom
Wellcome Trust Clinical Research Facility, Addenbrooke's Hospital
Cambridge, United Kingdom, CB2 0QQ
Sponsors and Collaborators
Cambridge University Hospitals NHS Foundation Trust
University of Cambridge
Juvenile Diabetes Research Foundation
National Institute for Health Research, United Kingdom
Wellcome Trust
Investigators
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Principal Investigator: Frank Waldron-Lynch University of Cambridge
More Information
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Additional Information:

Publications of Results:

Other Publications:

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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Responsible Party: Dr Frank Waldron-Lynch, Academic Consultant Endocrinologist, Cambridge University Hospitals NHS Foundation Trust
ClinicalTrials.gov Identifier: NCT01827735    
Other Study ID Numbers: A092737
ISRCTN27852285 ( Registry Identifier: ISRCTN )
First Posted: April 10, 2013    Key Record Dates
Last Update Posted: June 23, 2015
Last Verified: June 2015
Keywords provided by Dr Frank Waldron-Lynch, Cambridge University Hospitals NHS Foundation Trust:
Interleukin 2
Type 1 diabetes
T regulatory cells
Adaptive trial
Additional relevant MeSH terms:
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Diabetes Mellitus
Diabetes Mellitus, Type 1
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Autoimmune Diseases
Immune System Diseases
 Aldesleukin
Antineoplastic Agents
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents