Glucocorticoids and Skin Healing in Diabetes (GC-SHealD)

University of Leeds

Status and phase: Completed; Phase 2

Conditions: Diabetes Mellitus, Type 2

Treatments: Drug: Placebo; Drug: AZD4017

Study type: Interventional

Funder types: Other

Identifiers

NCT03313297

ED17/93260

Details and patient eligibility

About

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.

Full 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.

Enrollment: 28 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Able and willing to consent
2. Type 2 diabetes with HbA1c ≤11% (≤97 mmol/mol) at screening while taking standard therapy at a stable dose for ≥10 weeks

Exclusion criteria

1. Women of child-bearing potential
2. Active leg/foot ulceration
3. Clinically relevant acute electrocardiogram anomalies
4. Uncontrolled hypertension
5. Endocrine disorder (other than type 2 diabetes ), including type 1 or secondary diabetes (except treated hypothyroidism)
6. Gilbert's disease
7. Alanine aminotransferase and/or aspartate aminotransferase and/or alkaline phosphatase >1.5x upper limit of normal (ULN)
8. Bilirubin >1.5x ULN
9. Estimated glomerular filtration rate <45 ml/min/m2
10. Creatine kinase >2x ULN
11. Drug abuse within the last year
12. Any glucocorticoid treatment within 3 months of screening
13. Anti-coagulant medication
14. Probenecid therapy
15. Medical/surgical procedure or trauma during drug administration or one week after drug cessation (excluding skin biopsies)
16. Involvement in trial planning and/or conduct
17. Participation in other clinical study within 1 month
18. Deemed inappropriate to participate by the trial team

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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28 participants in 2 patient groups, including a placebo group

AZD4017

Active Comparator group

Description:

400mg oral AZD4017 twice daily for 35 days

Treatment:

Drug: AZD4017

Placebo

Placebo Comparator group

Description:

A placebo tablet containing microcrystalline cellulose and sodium stearyl fumarate to match the active tablets in size, shape and colour.

Treatment:

Drug: Placebo