- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01827735
Regulatory T Cells in Type 1 Diabetes Patients Treated With IL-2 (DILT1D)
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
Study Type
Enrollment (Actual)
Phase
- Phase 2
- Phase 1
Contacts and Locations
Study Locations
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Cambridge, United Kingdom, CB2 0QQ
- Wellcome Trust Clinical Research Facility, Addenbrooke's Hospital
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
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
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
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Fluorescence-activated cell sorting assay
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From Day 0 to Day 60
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
T regulatory cell phenotype and stability
Time Frame: From Day 0 to Day 60
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Fluorescence-activated cell sorting assay
|
From Day 0 to Day 60
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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
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Fluorescence-activated cell sorting assay
|
From Day 0 - Day 60
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T regulatory cell function
Time Frame: From Day 0 - Day 60
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T suppression assay
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From Day 0 - Day 60
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IL-2 pathway genotype
Time Frame: From Day 0 - Day 60
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DNA sequencing
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From Day 0 - Day 60
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Lymphocyte Subsets
Time Frame: From Day 0 to Day 60
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Complete blood count
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From Day 0 to Day 60
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Serum Cytokines
Time Frame: From Day 0 to Day 60
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Enzyme-linked immuno sorbent assay
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From Day 0 to Day 60
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Glycaemic control
Time Frame: From Day 0 to Day 60
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Self monitoring blood glucose readings, HbA1c, insulin usage
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From Day 0 to Day 60
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Number of Participants with Adverse Events as a Measure of Safety and Tolerability
Time Frame: From Day O to Day 60
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From Day O to Day 60
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Collaborators and Investigators
Collaborators
Investigators
- Principal Investigator: Frank Waldron-Lynch, University of Cambridge
Publications and helpful links
General 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.
- 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.
- 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.
Helpful Links
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- A092737
- ISRCTN27852285 (Registry Identifier: ISRCTN)
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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