Clinical trial NCT03313297: Glucocorticoids and Skin Healing in Diabetes (GC-SHealD)
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Diabetes Mellitus, Type 2
Keywords: skin
wound healing
11 beta-hydroxysteroid dehydrogenase type 1
Lead sponsor: University of Leeds
Sponsor class: OTHER
First posted: 2017-10-18
Enrollment: 28
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Double-blind, randomised, parallel group, placebo-controlled phase II pilot trial
Primary purpose: TREATMENT

Brief 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.

Eligibility criteria: 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

Primary outcomes:
measure: Skin 11β-HSD1 activity
timeFrame: Change between day 0 and day 28
Secondary outcomes:
measure: Urinary cortisol / cortisone metabolites
timeFrame: Change between day 0 and day 35
measure: AZD4017 in plasma
timeFrame: Change between day 0 and day 28
measure: AZD4017 in skin
timeFrame: Change between day 0 and day 28
measure: Discontinuation due to Adverse Event
timeFrame: Day 42
measure: Body mass index
timeFrame: Change between day 0 and day 35
measure: Waist-hip ratio
timeFrame: Change between day 0 and day 35
measure: Blood pressure (sphygmomanometer)
timeFrame: Change between day 0 and day 35
measure: Sudomotor function
timeFrame: Change between day 0 and day 35
measure: Skin hydration
timeFrame: Change between day 0 and day 35
measure: Epidermal barrier function
timeFrame: Change between day 0 and day 35
measure: Epidermal barrier integrity
timeFrame: Change between day 0 and day 28
measure: Skin thickness
timeFrame: Change between day 0 and day 35
measure: Wound healing
timeFrame: Change between day 0 and day 2
measure: Wound healing
timeFrame: Change between day 0 and day 7
measure: Wound healing
timeFrame: Change between day 28 and day 30
measure: Wound healing
timeFrame: Change between day 28 and day 35
measure: Skin RNA-seq gene expression profiling
timeFrame: Change between day 0 and day 28
Other outcomes:
Locations:
city: Leeds
country: United Kingdom
facility: Leeds Teaching Hospitals Trust
Study officials:
References: