Skip to main content
OpenTrials
Completed

NCT Number: NCT03313297

Glucocorticoids and Skin Healing in Diabetes (GC-SHealD)

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.

Completed

Looking for future studies?

Notify Me

Key information

Conditions

Diabetes Mellitus, Type 2 Diabetes Mellitus Endocrine System Diseases Glucose Metabolism Disorders Metabolic Diseases Nutritional and Metabolic Diseases

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Leeds Teaching Hospitals Trust

Leeds, LS9 7TF, United Kingdom

About this study

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

  • Oral AZD4017 inhibits 11β-HSD1 activity in skin
  • AZD4017 is safe and well-tolerated in patient with T2DM
  • Oral AZD4017 regulates skin function
  • 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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

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

Exclusion criteria

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

Treatment and study plan

AZD4017

Drug

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.

Placebo

Drug

Matching placebo

Primary outcomes

  1. Skin 11β-HSD1 activity

    Time frame: Change between day 0 and day 28

    Enzyme activity radioassay to evaluate AZD4107 efficacy in skin

Secondary outcomes

  1. Urinary cortisol / cortisone metabolites

    Time frame: Change between day 0 and day 35

    Urine samples for tetrahydrocortisol / tetrahydrocortisone metabolite ratios to evaluate systemic AZD4107 efficacy

  2. AZD4017 in plasma

    Time frame: Change between day 0 and day 28

    Quantification of AZD4017 concentration in plasma to evaluate systemic AZD4107 exposure

  3. AZD4017 in skin

    Time frame: Change between day 0 and day 28

    Quantification of AZD4017 concentration in plasma to evaluate skin AZD4107 exposure

  4. Discontinuation due to Adverse Event

    Time frame: Day 42

    Adverse Event-related participant withdrawals to evaluate safety

  5. Body mass index

    Time frame: Change between day 0 and day 35

    Body mass index to evaluate safety

  6. Waist-hip ratio

    Time frame: Change between day 0 and day 35

    Waist-hip ratio to evaluate safety

  7. Blood pressure (sphygmomanometer)

    Time frame: Change between day 0 and day 35

    Blood pressure to evaluate safety

  8. Sudomotor function

    Time frame: Change between day 0 and day 35

    Conducted with a Sudoscan device to measure c-fiber innervation in hands and feet for skin function

  9. Skin hydration

    Time frame: Change between day 0 and day 35

    Conducted with a Corneometer device to measure skin water content for skin function

  10. Epidermal barrier function

    Time frame: Change between day 0 and day 35

    Conducted with a Tewameter device to measure skin trans-epidermal water loss for skin function

  11. Epidermal barrier integrity

    Time frame: Change between day 0 and day 28

    Conducted by tape tripping to a pre-determined trans-epidermal water loss rate for skin function

  12. Skin thickness

    Time frame: Change between day 0 and day 35

    Conducted by Optical Coherence Tomography imaging for skin function

  13. Wound healing

    Time frame: Change between day 0 and day 2

    Conducted by Optical Coherence Tomography imaging for skin function

  14. Wound healing

    Time frame: Change between day 0 and day 7

    Conducted by Optical Coherence Tomography imaging for skin function

  15. Wound healing

    Time frame: Change between day 28 and day 30

    Conducted by Optical Coherence Tomography imaging for skin function

  16. Wound healing

    Time frame: Change between day 28 and day 35

    Conducted by Optical Coherence Tomography imaging for skin function

  17. Skin RNA-seq gene expression profiling

    Time frame: Change between day 0 and day 28

    For skin function

Sponsors and collaborators

Lead sponsor

University of Leeds

Other

Registry information

Official study 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

Acronym: GC-SHealD

Important dates

Study start
2018
Primary completion
2019
Study completion
2019
First posted
Oct 18, 2017
Registry last updated
Mar 22, 2019

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Related clinical trials

Published trials that share one or more normalized conditions with this study.