Back to resultsGlucocorticoids and Skin Healing in Diabetes (GC-SHealD) (GC-SHealD)
Primary Purpose
Diabetes Mellitus, Type 2
Status
Completed
Phase
Phase 2
Locations
United Kingdom
Study Type
Interventional
Intervention
AZD4017
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Diabetes Mellitus, Type 2 focused on measuring skin, wound healing, 11 beta-hydroxysteroid dehydrogenase type 1
Eligibility Criteria
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
Sites / Locations
- Leeds Teaching Hospitals Trust
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Placebo Comparator
Arm Label
AZD4017
Placebo
Arm Description
400mg oral AZD4017 twice daily for 35 days
A placebo tablet containing microcrystalline cellulose and sodium stearyl fumarate to match the active tablets in size, shape and colour.
Outcomes
Primary Outcome Measures
Skin 11β-HSD1 activity
Enzyme activity radioassay to evaluate AZD4107 efficacy in skin
Secondary Outcome Measures
Urinary cortisol / cortisone metabolites
Urine samples for tetrahydrocortisol / tetrahydrocortisone metabolite ratios to evaluate systemic AZD4107 efficacy
AZD4017 in plasma
Quantification of AZD4017 concentration in plasma to evaluate systemic AZD4107 exposure
AZD4017 in skin
Quantification of AZD4017 concentration in plasma to evaluate skin AZD4107 exposure
Discontinuation due to Adverse Event
Adverse Event-related participant withdrawals to evaluate safety
Body mass index
Body mass index to evaluate safety
Waist-hip ratio
Waist-hip ratio to evaluate safety
Blood pressure (sphygmomanometer)
Blood pressure to evaluate safety
Sudomotor function
Conducted with a Sudoscan device to measure c-fiber innervation in hands and feet for skin function
Skin hydration
Conducted with a Corneometer device to measure skin water content for skin function
Epidermal barrier function
Conducted with a Tewameter device to measure skin trans-epidermal water loss for skin function
Epidermal barrier integrity
Conducted by tape tripping to a pre-determined trans-epidermal water loss rate for skin function
Skin thickness
Conducted by Optical Coherence Tomography imaging for skin function
Wound healing
Conducted by Optical Coherence Tomography imaging for skin function
Wound healing
Conducted by Optical Coherence Tomography imaging for skin function
Wound healing
Conducted by Optical Coherence Tomography imaging for skin function
Wound healing
Conducted by Optical Coherence Tomography imaging for skin function
Skin RNA-seq gene expression profiling
For skin function
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03313297
Brief Title
Glucocorticoids and Skin Healing in Diabetes (GC-SHealD)
Acronym
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
2. Study Status
Record Verification Date
March 2019
Overall Recruitment Status
Completed
Study Start Date
April 10, 2018 (Actual)
Primary Completion Date
February 27, 2019 (Actual)
Study Completion Date
March 13, 2019 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Leeds
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
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
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Diabetes Mellitus, Type 2
Keywords
skin, wound healing, 11 beta-hydroxysteroid dehydrogenase type 1
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Model Description
Double-blind, randomised, parallel group, placebo-controlled phase II pilot trial
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Masking Description
Treatment groups will be allocated in a double-blind manner. Participants will be blinded to the treatment they receive (placebo or drug) throughout all stages of the study. Investigators will also be blinded to the treatment until all samples have been collected and processed. Blinding will be generated by a dedicated trials pharmacy representative who is not otherwise associated with this study.
Allocation
Randomized
Enrollment
28 (Actual)
8. Arms, Groups, and Interventions
Arm Title
AZD4017
Arm Type
Active Comparator
Arm Description
400mg oral AZD4017 twice daily for 35 days
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
A placebo tablet containing microcrystalline cellulose and sodium stearyl fumarate to match the active tablets in size, shape and colour.
Intervention Type
Drug
Intervention Name(s)
AZD4017
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Matching placebo
Primary Outcome Measure Information:
Title
Skin 11β-HSD1 activity
Description
Enzyme activity radioassay to evaluate AZD4107 efficacy in skin
Time Frame
Change between day 0 and day 28
Secondary Outcome Measure Information:
Title
Urinary cortisol / cortisone metabolites
Description
Urine samples for tetrahydrocortisol / tetrahydrocortisone metabolite ratios to evaluate systemic AZD4107 efficacy
Time Frame
Change between day 0 and day 35
Title
AZD4017 in plasma
Description
Quantification of AZD4017 concentration in plasma to evaluate systemic AZD4107 exposure
Time Frame
Change between day 0 and day 28
Title
AZD4017 in skin
Description
Quantification of AZD4017 concentration in plasma to evaluate skin AZD4107 exposure
Time Frame
Change between day 0 and day 28
Title
Discontinuation due to Adverse Event
Description
Adverse Event-related participant withdrawals to evaluate safety
Time Frame
Day 42
Title
Body mass index
Description
Body mass index to evaluate safety
Time Frame
Change between day 0 and day 35
Title
Waist-hip ratio
Description
Waist-hip ratio to evaluate safety
Time Frame
Change between day 0 and day 35
Title
Blood pressure (sphygmomanometer)
Description
Blood pressure to evaluate safety
Time Frame
Change between day 0 and day 35
Title
Sudomotor function
Description
Conducted with a Sudoscan device to measure c-fiber innervation in hands and feet for skin function
Time Frame
Change between day 0 and day 35
Title
Skin hydration
Description
Conducted with a Corneometer device to measure skin water content for skin function
Time Frame
Change between day 0 and day 35
Title
Epidermal barrier function
Description
Conducted with a Tewameter device to measure skin trans-epidermal water loss for skin function
Time Frame
Change between day 0 and day 35
Title
Epidermal barrier integrity
Description
Conducted by tape tripping to a pre-determined trans-epidermal water loss rate for skin function
Time Frame
Change between day 0 and day 28
Title
Skin thickness
Description
Conducted by Optical Coherence Tomography imaging for skin function
Time Frame
Change between day 0 and day 35
Title
Wound healing
Description
Conducted by Optical Coherence Tomography imaging for skin function
Time Frame
Change between day 0 and day 2
Title
Wound healing
Description
Conducted by Optical Coherence Tomography imaging for skin function
Time Frame
Change between day 0 and day 7
Title
Wound healing
Description
Conducted by Optical Coherence Tomography imaging for skin function
Time Frame
Change between day 28 and day 30
Title
Wound healing
Description
Conducted by Optical Coherence Tomography imaging for skin function
Time Frame
Change between day 28 and day 35
Title
Skin RNA-seq gene expression profiling
Description
For skin function
Time Frame
Change between day 0 and day 28
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Facility Information:
Facility Name
Leeds Teaching Hospitals Trust
City
Leeds
ZIP/Postal Code
LS9 7TF
Country
United Kingdom
12. IPD Sharing Statement
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Glucocorticoids and Skin Healing in Diabetes (GC-SHealD)
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