Receptor Trafficking in Incretin Action (RETRO study)
Research type
Research Study
Full title
Receptor Trafficking in Incretin Action (RETRO study)
IRAS ID
239932
Contact name
Stephen Bloom
Contact email
Sponsor organisation
Imperial College London
Duration of Study in the UK
2 years, 0 months, 1 days
Research summary
This is a study designed to investigate what role “trafficking” plays in controlling the effects of the glucagon-like peptide-1 (GLP-1) receptor. The GLP-1 receptor is a form of switch found on particular cells in the body, and has a number of effects, including making us feel full and allowing the body to make insulin to control blood glucose (sugar). “Trafficking” refers to the movement of receptors to and from the cell surface. When certain compounds, such as the hormone GLP-1, “activate” the GLP-1 receptor they cause it to disappear from the surface of cells – a form of trafficking known as “internalisation”. We suspect internalisation could make the body less responsive to GLP-1 over time ("tachyphylaxis").
To study this further, we designed molecules which are similar to GLP-1 but differ in how much internalisation they can produce. In this study, to be conducted in healthy volunteers, we plan to administer these molecules and monitor their effects on appetite and blood glucose over several hours. There will be three sub-studies, each of which addresses a particular aspect of GLP-1 biology. Each sub-study is further divided into two phases: the first phase (“dose finding”) aims to confirm the doses of each compound which give equivalent effects in the short term; these doses will then be tested over a slightly longer time-frame in the “double-blind” phase of the sub-study. This way, we can observe if any internalisation-related differences in effect emerge with time.
As part of a sub-study phase, participants will attend our research unit for three separate half-day to day-long visits, during which they will receive an injection of a fast-internalising compound (“exendin-4”), a slow-internalising compound (“exendin-phe1”), or an inactive placebo.
We hope the information gained from this study will in the future assist with development of better treatments for diabetes and obesity.
REC name
London - West London & GTAC Research Ethics Committee
REC reference
18/LO/0311
Date of REC Opinion
16 May 2018
REC opinion
Further Information Favourable Opinion