Glucocorticoids and Skin Healing in Diabetes (GC-SHealD) (GC-SHealD)
21 mars 2019 mis à jour par: 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.
Aperçu de l'étude
Statut
Complété
Les conditions
Intervention / Traitement
Description détaillée
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.
Type d'étude
Interventionnel
Inscription (Réel)
28
Phase
- Phase 2
Contacts et emplacements
Cette section fournit les coordonnées de ceux qui mènent l'étude et des informations sur le lieu où cette étude est menée.
Lieux d'étude
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Leeds, Royaume-Uni, LS9 7TF
- Leeds Teaching Hospitals Trust
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Critères de participation
Les chercheurs recherchent des personnes qui correspondent à une certaine description, appelée critères d'éligibilité. Certains exemples de ces critères sont l'état de santé général d'une personne ou des traitements antérieurs.
Critère d'éligibilité
Âges éligibles pour étudier
18 ans et plus (Adulte, Adulte plus âgé)
Accepte les volontaires sains
Non
Sexes éligibles pour l'étude
Tout
La 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
Plan d'étude
Cette section fournit des détails sur le plan d'étude, y compris la façon dont l'étude est conçue et ce que l'étude mesure.
Comment l'étude est-elle conçue ?
Détails de conception
- Objectif principal: Traitement
- Répartition: Randomisé
- Modèle interventionnel: Affectation parallèle
- Masquage: Quadruple
Armes et Interventions
Groupe de participants / Bras |
Intervention / Traitement |
|---|---|
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Comparateur actif: AZD4017
400mg oral AZD4017 twice daily for 35 days
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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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Comparateur placebo: 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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Placebo correspondant
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Que mesure l'étude ?
Principaux critères de jugement
Mesure des résultats |
Description de la mesure |
Délai |
|---|---|---|
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Skin 11β-HSD1 activity
Délai: 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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Mesures de résultats secondaires
Mesure des résultats |
Description de la mesure |
Délai |
|---|---|---|
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Urinary cortisol / cortisone metabolites
Délai: Change between day 0 and day 35
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Urine samples for tetrahydrocortisol / tetrahydrocortisone metabolite ratios to evaluate systemic AZD4107 efficacy
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Change between day 0 and day 35
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AZD4017 in plasma
Délai: Change between day 0 and day 28
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Quantification of AZD4017 concentration in plasma to evaluate systemic AZD4107 exposure
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Change between day 0 and day 28
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AZD4017 in skin
Délai: Change between day 0 and day 28
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Quantification of AZD4017 concentration in plasma to evaluate skin AZD4107 exposure
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Change between day 0 and day 28
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Discontinuation due to Adverse Event
Délai: Day 42
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Adverse Event-related participant withdrawals to evaluate safety
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Day 42
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Body mass index
Délai: Change between day 0 and day 35
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Body mass index to evaluate safety
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Change between day 0 and day 35
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Waist-hip ratio
Délai: Change between day 0 and day 35
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Waist-hip ratio to evaluate safety
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Change between day 0 and day 35
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Blood pressure (sphygmomanometer)
Délai: Change between day 0 and day 35
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Blood pressure to evaluate safety
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Change between day 0 and day 35
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Sudomotor function
Délai: 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
Délai: 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
Délai: 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
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Change between day 0 and day 35
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Epidermal barrier integrity
Délai: 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
Délai: Change between day 0 and day 35
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Conducted by Optical Coherence Tomography imaging for skin function
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Change between day 0 and day 35
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Wound healing
Délai: 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
Délai: 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
Délai: 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
Délai: 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
Délai: 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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Collaborateurs et enquêteurs
C'est ici que vous trouverez les personnes et les organisations impliquées dans cette étude.
Parrainer
Dates d'enregistrement des études
Ces dates suivent la progression des dossiers d'étude et des soumissions de résultats sommaires à ClinicalTrials.gov. Les dossiers d'étude et les résultats rapportés sont examinés par la Bibliothèque nationale de médecine (NLM) pour s'assurer qu'ils répondent à des normes de contrôle de qualité spécifiques avant d'être publiés sur le site Web public.
Dates principales de l'étude
Début de l'étude (Réel)
10 avril 2018
Achèvement primaire (Réel)
27 février 2019
Achèvement de l'étude (Réel)
13 mars 2019
Dates d'inscription aux études
Première soumission
5 octobre 2017
Première soumission répondant aux critères de contrôle qualité
17 octobre 2017
Première publication (Réel)
18 octobre 2017
Mises à jour des dossiers d'étude
Dernière mise à jour publiée (Réel)
22 mars 2019
Dernière mise à jour soumise répondant aux critères de contrôle qualité
21 mars 2019
Dernière vérification
1 mars 2019
Plus d'information
Termes liés à cette étude
Termes MeSH pertinents supplémentaires
Autres numéros d'identification d'étude
- ED17/93260
Informations sur les médicaments et les dispositifs, documents d'étude
Étudie un produit pharmaceutique réglementé par la FDA américaine
Non
Étudie un produit d'appareil réglementé par la FDA américaine
Non
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