- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03313297
Glucocorticoids and Skin Healing in Diabetes (GC-SHealD) (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
Study Overview
Status
Conditions
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
- 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.
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
-
-
-
Leeds, United Kingdom, LS9 7TF
- Leeds Teaching Hospitals Trust
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-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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
Study Plan
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
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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
Sponsor
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- ED17/93260
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
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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