TICSI version 0.6
Research type
Research Study
Full title
Targeting Iatrogenic Cushing’s Syndrome with 11β-hydroxysteroid dehydrogenase type 1 Inhibition
IRAS ID
212634
Contact name
Jeremy Tomlinson
Contact email
Sponsor organisation
University of Oxford, Clinical Trials and Research Governance
Eudract number
2016-003060-40
Duration of Study in the UK
1 years, 10 months, 31 days
Research summary
Research Summary
2-3% of the population of the UK are prescribed steroid treatment to treat a wide variety of conditions. Whilst steroid treatment is very effective, it is associated with significant side effects that can include weight gain, the development of diabetes, high blood pressure, fat in the liver and thinning of the muscles. Currently there are no treatments available to limit these side effects.In working leading up to this study, we have shown that an enzyme called 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) generates additional steroid to those that are administered and this can further amplify the detrimental actions of steroids (notably in muscle, liver and fat). We have shown that animals that lack 11β-HSD1 are protected from the side effects of administered steroids. We believe therefore that inhibiting 11β-HSD1 may be an entirely new way to limit the side effects of prescribed steroids without compromising their desirable, anti-inflammatory actions.
An 11β-HSD1 inhibitor, AZD4017, has been developed by AstraZeneca, and in a partnership with University of Oxford, we will use this drug in healthy volunteers to see if we can limit the side effects of steroid treatment. Volunteers will be treated with a commonly prescribed steroid, prednisolone, alongside either AZD4014 or a placebo (dummy pill). Investigations will be performed before and after one week of treatment. The tests that we will perform will aim to show that in those volunteers treated with AZD4017, the effects of prednisolone to increase the risk of diabetes, thin the muscles and increase fat are less than in the placebo group. We aim to show that the desirable, anti-inflammatory actions of prednisolone will be no different between AZD4017 and placebo treated groups.
Lay Summary of results
The TICSI (Targeting Iatrogenic Cushing's Syndrome with 11-hydroxysteroid dehydrogenase type 1 Inhibition) trial has shown, for the first time that treatment with the 11-HSD1 inhibitor, AZD4014, can prevent many of the harmful side effects associated with the use of the most commonly prescribed oral steroid, prednisolone. Over a 7-day period, we were able to show that the adverse effects of prednisolone on glucose levels, bone health, blood lipid levels and blood pressure were significantly improved. Importantly, the majority of the desirable, anti-inflammatory actions of prednisolone were retained. Overall, the TICSI study provides the first evidence in humans to show that 11-HSD1 inhibition might offer a realistic strategy to prevent the significant side effects associated with prescribed steroids
REC name
East of England - Cambridge East Research Ethics Committee
REC reference
16/EE/0550
Date of REC Opinion
13 Jan 2017
REC opinion
Further Information Favourable Opinion