- ICH GCP
- Register voor klinische proeven in de VS.
- Klinische proef 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
Studie Overzicht
Toestand
Conditie
Interventie / Behandeling
Gedetailleerde beschrijving
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.
Studietype
Inschrijving (Werkelijk)
Fase
- Fase 2
Contacten en locaties
Studie Locaties
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Leeds, Verenigd Koninkrijk, LS9 7TF
- Leeds Teaching Hospitals Trust
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Deelname Criteria
Geschiktheidscriteria
Leeftijden die in aanmerking komen voor studie
Accepteert gezonde vrijwilligers
Geslachten die in aanmerking komen voor studie
Beschrijving
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
Studie plan
Hoe is de studie opgezet?
Ontwerpdetails
- Primair doel: Behandeling
- Toewijzing: Gerandomiseerd
- Interventioneel model: Parallelle opdracht
- Masker: Verviervoudigen
Wapens en interventies
Deelnemersgroep / Arm |
Interventie / Behandeling |
---|---|
Actieve vergelijker: 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.
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Placebo-vergelijker: Placebo
A placebo tablet containing microcrystalline cellulose and sodium stearyl fumarate to match the active tablets in size, shape and colour.
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Bijpassende placebo
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Wat meet het onderzoek?
Primaire uitkomstmaten
Uitkomstmaat |
Maatregel Beschrijving |
Tijdsspanne |
---|---|---|
Skin 11β-HSD1 activity
Tijdsspanne: Change between day 0 and day 28
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Enzyme activity radioassay to evaluate AZD4107 efficacy in skin
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Change between day 0 and day 28
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Secundaire uitkomstmaten
Uitkomstmaat |
Maatregel Beschrijving |
Tijdsspanne |
---|---|---|
Urinary cortisol / cortisone metabolites
Tijdsspanne: 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
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AZD4017 in plasma
Tijdsspanne: Change between day 0 and day 28
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Quantification of AZD4017 concentration in plasma to evaluate systemic AZD4107 exposure
|
Change between day 0 and day 28
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AZD4017 in skin
Tijdsspanne: 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
Tijdsspanne: Day 42
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Adverse Event-related participant withdrawals to evaluate safety
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Day 42
|
Body mass index
Tijdsspanne: Change between day 0 and day 35
|
Body mass index to evaluate safety
|
Change between day 0 and day 35
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Waist-hip ratio
Tijdsspanne: Change between day 0 and day 35
|
Waist-hip ratio to evaluate safety
|
Change between day 0 and day 35
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Blood pressure (sphygmomanometer)
Tijdsspanne: Change between day 0 and day 35
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Blood pressure to evaluate safety
|
Change between day 0 and day 35
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Sudomotor function
Tijdsspanne: Change between day 0 and day 35
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Conducted with a Sudoscan device to measure c-fiber innervation in hands and feet for skin function
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Change between day 0 and day 35
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Skin hydration
Tijdsspanne: Change between day 0 and day 35
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Conducted with a Corneometer device to measure skin water content for skin function
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Change between day 0 and day 35
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Epidermal barrier function
Tijdsspanne: Change between day 0 and day 35
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Conducted with a Tewameter device to measure skin trans-epidermal water loss for skin function
|
Change between day 0 and day 35
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Epidermal barrier integrity
Tijdsspanne: Change between day 0 and day 28
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Conducted by tape tripping to a pre-determined trans-epidermal water loss rate for skin function
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Change between day 0 and day 28
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Skin thickness
Tijdsspanne: 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
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Wound healing
Tijdsspanne: Change between day 0 and day 2
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Conducted by Optical Coherence Tomography imaging for skin function
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Change between day 0 and day 2
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Wound healing
Tijdsspanne: Change between day 0 and day 7
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Conducted by Optical Coherence Tomography imaging for skin function
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Change between day 0 and day 7
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Wound healing
Tijdsspanne: Change between day 28 and day 30
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Conducted by Optical Coherence Tomography imaging for skin function
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Change between day 28 and day 30
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Wound healing
Tijdsspanne: Change between day 28 and day 35
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Conducted by Optical Coherence Tomography imaging for skin function
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Change between day 28 and day 35
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Skin RNA-seq gene expression profiling
Tijdsspanne: Change between day 0 and day 28
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For skin function
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Change between day 0 and day 28
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Medewerkers en onderzoekers
Sponsor
Studie record data
Bestudeer belangrijke data
Studie start (Werkelijk)
Primaire voltooiing (Werkelijk)
Studie voltooiing (Werkelijk)
Studieregistratiedata
Eerst ingediend
Eerst ingediend dat voldeed aan de QC-criteria
Eerst geplaatst (Werkelijk)
Updates van studierecords
Laatste update geplaatst (Werkelijk)
Laatste update ingediend die voldeed aan QC-criteria
Laatst geverifieerd
Meer informatie
Termen gerelateerd aan deze studie
Aanvullende relevante MeSH-voorwaarden
Andere studie-ID-nummers
- ED17/93260
Informatie over medicijnen en apparaten, studiedocumenten
Bestudeert een door de Amerikaanse FDA gereguleerd geneesmiddel
Bestudeert een door de Amerikaanse FDA gereguleerd apparaatproduct
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