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Type 1 DiabetesPhase 1/2DILT1DNCT01827735

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

A Phase 1/2 study testing Aldesleukin (Proleukin) in people with Type 1 Diabetes, run by Cambridge University Hospitals NHS Foundation Trust at 1 site in United Kingdom.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 to 50 years
Conditions the study is for
Type 1 Diabetes
What is being tested?
Aldesleukin (Proleukin)
Type of treatment
Injection or infusion
How many people
40 participants
Where
1 siteUnited Kingdom
Study dates
Mar 2013to May 2014
Phase
Phase 1/2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 50 years
  • All sexes
  • No healthy volunteers
  • Adult

Who may be able to join

  • 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)

Who cannot join

  • 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
Show all 14Show fewer
  • 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

Trial locations and contacts

1 site in 1 country.

United Kingdom1 site

  • Wellcome Trust Clinical Research Facility, Addenbrooke's Hospital

    Cambridge, CB2 0QQ

Other trials in United Kingdom

About this study

Official title: 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.

Conditions
Type 1 Diabetes
Being tested
Aldesleukin (Proleukin)
Keywords
Interleukin 2, Type 1 diabetes, T regulatory cells, Adaptive trial
Medical subject headings
Diabetes Mellitus, Type 1

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Aldesleukin (Proleukin)Drug

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

What is being measured

The primary outcome is the main question the study is designed to answer.

  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

    Measured: From Day 0 to Day 60

Secondary outcomes (10)

  1. T regulatory cell phenotype and stability

    Fluorescence-activated cell sorting assay

    Measured: From Day 0 to Day 60

  2. T effector cell number and phenotype

    Fluorescence-activated cell sorting assay

    Measured: From Day 0 - Day 60

  3. T cell subset proliferation and populations

    Fluorescence-activated cell sorting assay

    Measured: From Day 0 - Day 60

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

    Fluorescence-activated cell sorting assay

    Measured: From Day 0 - Day 60

  5. T regulatory cell function

    T suppression assay

    Measured: From Day 0 - Day 60

  6. IL-2 pathway genotype

    DNA sequencing

    Measured: From Day 0 - Day 60

  7. Lymphocyte Subsets

    Complete blood count

    Measured: From Day 0 to Day 60

  8. Serum Cytokines

    Enzyme-linked immuno sorbent assay

    Measured: From Day 0 to Day 60

  9. Glycaemic control

    Self monitoring blood glucose readings, HbA1c, insulin usage

    Measured: From Day 0 to Day 60

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

    Measured: From Day O to Day 60

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted10 Apr 2013 (estimated)
  2. Study startMar 2013
  3. Primary completionMay 2014
  4. Study completionMay 2014

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Basic science
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
40 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01827735
Sponsor's protocol ID
A092737
Other IDs
ISRCTN27852285
Acronym
DILT1D
Status last verified
Jun 2015
First submitted
4 Apr 2013
Last updated
23 Jun 2015
Results posted
No
Data monitoring committee
No

Publications

  • 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.

    PubMed 24898091

  • 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.

    PubMed 25881192

  • 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.

    PubMed 27727279

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Aldesleukin (Proleukin) in people with Type 1 Diabetes, run by Cambridge University Hospitals NHS Foundation Trust at 1 site in United Kingdom.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 23 Jun 2015. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01827735, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Jun 2015.

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