NCT01827735

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
40

participants targeted

Target at P50-P75 for phase_1

Timeline
Completed

Started Mar 2013

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

March 1, 2013

Completed
1 month until next milestone

First Submitted

Initial submission to the registry

April 4, 2013

Completed
6 days until next milestone

First Posted

Study publicly available on registry

April 10, 2013

Completed
1.1 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

May 1, 2014

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

May 1, 2014

Completed
Last Updated

June 23, 2015

Status Verified

June 1, 2015

Enrollment Period

1.2 years

First QC Date

April 4, 2013

Last Update Submit

June 22, 2015

Conditions

Type 1 Diabetes

Keywords

Interleukin 2Type 1 diabetesT regulatory cellsAdaptive trial

Outcome Measures

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.

    Fluorescence-activated cell sorting assay

    From Day 0 to Day 60

Secondary Outcomes (10)

  • T regulatory cell phenotype and stability

    From Day 0 to Day 60

  • T effector cell number and phenotype

    From Day 0 - Day 60

  • T cell subset proliferation and populations

    From Day 0 - Day 60

  • Intracellular T cell and natural killer(NK) cell signalling

    From Day 0 - Day 60

  • T regulatory cell function

    From Day 0 - Day 60

  • +5 more secondary outcomes

Interventions

Aldesleukin (Proleukin)DRUG

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

Eligibility Criteria

Age18 Years - 50 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64)

You may qualify if:

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

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Wellcome Trust Clinical Research Facility, Addenbrooke's Hospital

Cambridge, CB2 0QQ, United Kingdom

Location

Related Publications (3)

  • Waldron-Lynch F, Kareclas P, Irons K, Walker NM, Mander A, Wicker LS, Todd JA, Bond S. Rationale and study design of the Adaptive study of IL-2 dose on regulatory T cells in type 1 diabetes (DILT1D): a non-randomised, open label, adaptive dose finding trial. BMJ Open. 2014 Jun 4;4(6):e005559. doi: 10.1136/bmjopen-2014-005559.

    PMID: 24898091BACKGROUND

  • Heywood J, Evangelou M, Goymer D, Kennet J, Anselmiova K, Guy C, O'Brien C, Nutland S, Brown J, Walker NM, Todd JA, Waldron-Lynch F. Effective recruitment of participants to a phase I study using the internet and publicity releases through charities and patient organisations: analysis of the adaptive study of IL-2 dose on regulatory T cells in type 1 diabetes (DILT1D). Trials. 2015 Mar 11;16:86. doi: 10.1186/s13063-015-0583-7.

    PMID: 25881192RESULT

  • Todd JA, Evangelou M, Cutler AJ, Pekalski ML, Walker NM, Stevens HE, Porter L, Smyth DJ, Rainbow DB, Ferreira RC, Esposito L, Hunter KM, Loudon K, Irons K, Yang JH, Bell CJ, Schuilenburg H, Heywood J, Challis B, Neupane S, Clarke P, Coleman G, Dawson S, Goymer D, Anselmiova K, Kennet J, Brown J, Caddy SL, Lu J, Greatorex J, Goodfellow I, Wallace C, Tree TI, Evans M, Mander AP, Bond S, Wicker LS, Waldron-Lynch F. Regulatory T Cell Responses in Participants with Type 1 Diabetes after a Single Dose of Interleukin-2: A Non-Randomised, Open Label, Adaptive Dose-Finding Trial. PLoS Med. 2016 Oct 11;13(10):e1002139. doi: 10.1371/journal.pmed.1002139. eCollection 2016 Oct.

    PMID: 27727279DERIVED

Related Links

MeSH Terms

Conditions

Diabetes Mellitus, Type 1

Interventions

aldesleukin

Condition Hierarchy (Ancestors)

Diabetes MellitusGlucose Metabolism DisordersMetabolic DiseasesNutritional and Metabolic DiseasesEndocrine System DiseasesAutoimmune DiseasesImmune System Diseases

Study Officials

  • Frank Waldron-Lynch

    University of Cambridge

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NA
Masking
NONE
Purpose
BASIC SCIENCE
Intervention Model
SINGLE GROUP
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Academic Consultant Endocrinologist

Study Record Dates

First Submitted

April 4, 2013

First Posted

April 10, 2013

Study Start

March 1, 2013

Primary Completion

May 1, 2014

Study Completion

May 1, 2014

Last Updated

June 23, 2015

Record last verified: 2015-06

Locations

GB(1)