NCT03313297

Glucocorticoids and Skin Healing in Diabetes (GC-SHealD)

A Double-blind, Randomized, Placebo-controlled Phase II Pilot Trial Investigating Efficacy, Safety and Feasibility of 11β-hydroxysteroid Dehydrogenase Type 1 Inhibition by AZD4017 to Improve Skin Function and Wound Healing in Patients With Type 2 Diabetes

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 28 (actual)
• Sponsor: University of Leeds · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

The study aims to investigate effects of inhibiting glucocorticoid activation on skin function and wound healing in patients with type 2 diabetes. Half of patients will be given a drug to inhibit glucocorticoid activation and the other half will be given a placebo.

Detailed description

Glucocorticoids are known to impair skin function and wound healing which are also compromised in patients with type 2 diabetes. The enzyme 11 beta-hydroxysteroid dehydrogenase type 1 (11β-HSD1) activates glucocorticoids in target tissues including skin. Pre-clinical data demonstrate that 11β-HSD1 inhibition improves skin function and wound healing but this has not been investigated in man. Using the 11β-HSD1 inhibitor AZD4017, we will investigate if 1. Oral AZD4017 inhibits 11β-HSD1 activity in skin 2. AZD4017 is safe and well-tolerated in patient with T2DM 3. Oral AZD4017 regulates skin function 4. Systemic glucocorticoid levels and skin 11β-HSD1 activity, independently or in combination correlate with measures of skin function Study feasibility will also be assessed; if successful, data from this pilot study will inform power calculations for a future trial to investigate the ability of 11β-HSD1 inhibition to promote foot ulcer healing in type 2 diabetes.

Conditions

• Diabetes Mellitus, Type 2

Interventions

Type	Name	Description
DRUG	AZD4017	AZD4017 is a novel orally bioavailable small molecule inhibitor of 11β-HSD1 enzyme activity. It is potent and highly selective in vitro and in vivo. The half maximal inhibitory concentration (IC50) for inhibition of 11β-HSD1 activity (cortisone to cortisol conversion) is 2nM. AZD4017 is selective (\> 2000x) for 11β-HSD1 over human recombinant 11β-HSD2 and the closely-homologous enzymes 17β-hydroxysteroid dehydrogenase 1 and 17β-hydroxysteroid dehydrogenase 3 in vitro.
DRUG	Placebo	Matching placebo

Timeline

• Start date: 2018-04-10
• Primary completion: 2019-02-27
• Completion: 2019-03-13
• First posted: 2017-10-18
• Last updated: 2019-03-22

Locations

1 site across 1 country: United Kingdom