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

Type 1 Diabetes Clinical Trial

— DILT1D  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01827735
• Other study ID #: A092737
• Secondary ID: ISRCTN27852285
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: April 4, 2013
• Last updated: June 22, 2015
• Start date: March 2013
• Est. completion date: May 2014

Study information

• Verified date: June 2015
• Source: Cambridge University Hospitals NHS Foundation Trust
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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. 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 40
• Est. completion date: May 2014
• Est. primary completion date: May 2014
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 50 Years

Eligibility

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

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 1
• Type 1 Diabetes

Intervention

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

Locations

Country	Name	City	State
United Kingdom	Wellcome Trust Clinical Research Facility, Addenbrooke's Hospital	Cambridge

Sponsors (5)

Lead Sponsor	Collaborator
Cambridge University Hospitals NHS Foundation Trust	Juvenile Diabetes Research Foundation, National Institute for Health Research, United Kingdom, University of Cambridge, Wellcome Trust

Country where clinical trial is conducted

United Kingdom, 

References & Publications (2)

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 p — View Citation

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. — View Citation

Outcome

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

External Links

•   DILT1D trial facebook page
•   DILT1D trial Twitter update
•   DILT1D trial Web site