Glucocorticoids and Skin Healing in Diabetes (GC-SHealD) (GC-SHealD)

March 21, 2019 updated by: Ana Tiganescu, PhD, University of Leeds

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

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.

Study Overview

Status

Completed

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

28

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

      • Leeds, United Kingdom, LS9 7TF
        • Leeds Teaching Hospitals Trust

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: AZD4017
400mg oral AZD4017 twice daily for 35 days
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 Comparator: Placebo
A placebo tablet containing microcrystalline cellulose and sodium stearyl fumarate to match the active tablets in size, shape and colour.
Matching placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Skin 11β-HSD1 activity
Time Frame: Change between day 0 and day 28
Enzyme activity radioassay to evaluate AZD4107 efficacy in skin
Change between day 0 and day 28

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
Change between day 0 and day 35
AZD4017 in plasma
Time Frame: Change between day 0 and day 28
Quantification of AZD4017 concentration in plasma to evaluate systemic AZD4107 exposure
Change between day 0 and day 28
AZD4017 in skin
Time Frame: Change between day 0 and day 28
Quantification of AZD4017 concentration in plasma to evaluate skin AZD4107 exposure
Change between day 0 and day 28
Discontinuation due to Adverse Event
Time Frame: Day 42
Adverse Event-related participant withdrawals to evaluate safety
Day 42
Body mass index
Time Frame: Change between day 0 and day 35
Body mass index to evaluate safety
Change between day 0 and day 35
Waist-hip ratio
Time Frame: Change between day 0 and day 35
Waist-hip ratio to evaluate safety
Change between day 0 and day 35
Blood pressure (sphygmomanometer)
Time Frame: Change between day 0 and day 35
Blood pressure to evaluate safety
Change between day 0 and day 35
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
Change between day 0 and day 35
Skin hydration
Time Frame: Change between day 0 and day 35
Conducted with a Corneometer device to measure skin water content for skin function
Change between day 0 and day 35
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
Change between day 0 and day 35
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
Change between day 0 and day 28
Skin thickness
Time Frame: Change between day 0 and day 35
Conducted by Optical Coherence Tomography imaging for skin function
Change between day 0 and day 35
Wound healing
Time Frame: Change between day 0 and day 2
Conducted by Optical Coherence Tomography imaging for skin function
Change between day 0 and day 2
Wound healing
Time Frame: Change between day 0 and day 7
Conducted by Optical Coherence Tomography imaging for skin function
Change between day 0 and day 7
Wound healing
Time Frame: Change between day 28 and day 30
Conducted by Optical Coherence Tomography imaging for skin function
Change between day 28 and day 30
Wound healing
Time Frame: Change between day 28 and day 35
Conducted by Optical Coherence Tomography imaging for skin function
Change between day 28 and day 35
Skin RNA-seq gene expression profiling
Time Frame: Change between day 0 and day 28
For skin function
Change between day 0 and day 28

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

April 10, 2018

Primary Completion (Actual)

February 27, 2019

Study Completion (Actual)

March 13, 2019

Study Registration Dates

First Submitted

October 5, 2017

First Submitted That Met QC Criteria

October 17, 2017

First Posted (Actual)

October 18, 2017

Study Record Updates

Last Update Posted (Actual)

March 22, 2019

Last Update Submitted That Met QC Criteria

March 21, 2019

Last Verified

March 1, 2019

More Information

Terms related to this study

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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