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

June 22, 2015 updated by: Dr Frank Waldron-Lynch, Cambridge University Hospitals NHS Foundation Trust

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

40

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

      • Cambridge, United Kingdom, CB2 0QQ
        • Wellcome Trust Clinical Research Facility, Addenbrooke's Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 50 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Basic Science
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
From Day 0 to Day 60

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
T regulatory cell phenotype and stability
Time Frame: From Day 0 to Day 60
Fluorescence-activated cell sorting assay
From Day 0 to Day 60
T effector cell number and phenotype
Time Frame: From Day 0 - Day 60
Fluorescence-activated cell sorting assay
From Day 0 - Day 60
T cell subset proliferation and populations
Time Frame: From Day 0 - Day 60
Fluorescence-activated cell sorting assay
From Day 0 - Day 60
Intracellular T cell and natural killer(NK) cell signalling
Time Frame: From Day 0 - Day 60
Fluorescence-activated cell sorting assay
From Day 0 - Day 60
T regulatory cell function
Time Frame: From Day 0 - Day 60
T suppression assay
From Day 0 - Day 60
IL-2 pathway genotype
Time Frame: From Day 0 - Day 60
DNA sequencing
From Day 0 - Day 60
Lymphocyte Subsets
Time Frame: From Day 0 to Day 60
Complete blood count
From Day 0 to Day 60
Serum Cytokines
Time Frame: From Day 0 to Day 60
Enzyme-linked immuno sorbent assay
From Day 0 to Day 60
Glycaemic control
Time Frame: From Day 0 to Day 60
Self monitoring blood glucose readings, HbA1c, insulin usage
From Day 0 to Day 60
Number of Participants with Adverse Events as a Measure of Safety and Tolerability
Time Frame: From Day O to Day 60
From Day O to Day 60

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

March 1, 2013

Primary Completion (Actual)

May 1, 2014

Study Completion (Actual)

May 1, 2014

Study Registration Dates

First Submitted

April 4, 2013

First Submitted That Met QC Criteria

April 5, 2013

First Posted (Estimate)

April 10, 2013

Study Record Updates

Last Update Posted (Estimate)

June 23, 2015

Last Update Submitted That Met QC Criteria

June 22, 2015

Last Verified

June 1, 2015

More Information

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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