DILfrequency
Research type
Research Study
Full title
Adaptive study of IL-2 dose frequency on regulatory T cells in type 1 diabetes (DILfrequency)
IRAS ID
154589
Contact name
Frank Waldron-Lynch
Contact email
Sponsor organisation
Cambridge University Hospitals NHS Foundation Trust
Duration of Study in the UK
3 years, 0 months, 1 days
Research summary
Type 1 diabetes (T1D) is the most common severe chronic autoimmune disease worldwide with a rapidly increasing incidence and prevalence, occuring in adults and children equally. The aetiology of T1D is an autoimmune (loss of self-tolerance) mediated destruction of the insulin-producing pancreatic beta cells leading to insulin deficiency and the development of hyperglycaemia. Currently, medical management of T1D focuses on intensive insulin replacement therapy to limit complications such as retinopathy, nephropathy, neuropathy. Despite improvements in the last 93 years, 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 T1D have been found to encode proteins involved in immune regulation and function. In particular, several susceptibility proteins are involved in the interleukin 1 (IL-2) pathway that regulates T cell activation and tolerance to self antigens.
Aldesleukin (Proleukin) is a human recombinant IL-2 product produced by recombinant DNA technology using genetically engineered E.coli strain containing an analogue of the human IL-2 gene. There is substantial non-clinical, preclinical and clinical data that ultra low dose of 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 T1D it is essential that the optimum dose and frequency of IL-2 is determined. In our previous study (DILT1D) we determined the optimal doses of IL-2 to administer in order to increase T regulatory cells. The objective of this DIL frequency study is to determine the optimal dosing frequency of ultra low IL-2 needed to maximise Tregulatory cell function.REC name
East of England - Cambridge East Research Ethics Committee
REC reference
14/EE/1057
Date of REC Opinion
12 Aug 2014
REC opinion
Further Information Favourable Opinion