- ICH GCP
- Registro de ensayos clínicos de EE. UU.
- Ensayo clínico 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
Descripción general del estudio
Estado
Condiciones
Intervención / Tratamiento
Descripción detallada
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.
Tipo de estudio
Inscripción (Actual)
Fase
- Fase 2
Contactos y Ubicaciones
Ubicaciones de estudio
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Leeds, Reino Unido, LS9 7TF
- Leeds Teaching Hospitals Trust
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Criterios de participación
Criterio de elegibilidad
Edades elegibles para estudiar
Acepta Voluntarios Saludables
Géneros elegibles para el estudio
Descripción
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 de estudios
¿Cómo está diseñado el estudio?
Detalles de diseño
- Propósito principal: Tratamiento
- Asignación: Aleatorizado
- Modelo Intervencionista: Asignación paralela
- Enmascaramiento: Cuadruplicar
Armas e Intervenciones
Grupo de participantes/brazo |
Intervención / Tratamiento |
---|---|
Comparador activo: 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.
|
Comparador de placebos: 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 a juego
|
¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
---|---|---|
Skin 11β-HSD1 activity
Periodo de tiempo: Change between day 0 and day 28
|
Enzyme activity radioassay to evaluate AZD4107 efficacy in skin
|
Change between day 0 and day 28
|
Medidas de resultado secundarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
---|---|---|
Urinary cortisol / cortisone metabolites
Periodo de tiempo: 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
Periodo de tiempo: 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
Periodo de tiempo: 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
Periodo de tiempo: Day 42
|
Adverse Event-related participant withdrawals to evaluate safety
|
Day 42
|
Body mass index
Periodo de tiempo: Change between day 0 and day 35
|
Body mass index to evaluate safety
|
Change between day 0 and day 35
|
Waist-hip ratio
Periodo de tiempo: Change between day 0 and day 35
|
Waist-hip ratio to evaluate safety
|
Change between day 0 and day 35
|
Blood pressure (sphygmomanometer)
Periodo de tiempo: Change between day 0 and day 35
|
Blood pressure to evaluate safety
|
Change between day 0 and day 35
|
Sudomotor function
Periodo de tiempo: 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
Periodo de tiempo: 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
|
Epidermal barrier function
Periodo de tiempo: 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
Periodo de tiempo: 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
|
Change between day 0 and day 28
|
Skin thickness
Periodo de tiempo: 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
Periodo de tiempo: 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
Periodo de tiempo: 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
Periodo de tiempo: 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
Periodo de tiempo: Change between day 28 and day 35
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Conducted by Optical Coherence Tomography imaging for skin function
|
Change between day 28 and day 35
|
Skin RNA-seq gene expression profiling
Periodo de tiempo: Change between day 0 and day 28
|
For skin function
|
Change between day 0 and day 28
|
Colaboradores e Investigadores
Patrocinador
Fechas de registro del estudio
Fechas importantes del estudio
Inicio del estudio (Actual)
Finalización primaria (Actual)
Finalización del estudio (Actual)
Fechas de registro del estudio
Enviado por primera vez
Primero enviado que cumplió con los criterios de control de calidad
Publicado por primera vez (Actual)
Actualizaciones de registros de estudio
Última actualización publicada (Actual)
Última actualización enviada que cumplió con los criterios de control de calidad
Última verificación
Más información
Términos relacionados con este estudio
Términos MeSH relevantes adicionales
Otros números de identificación del estudio
- ED17/93260
Información sobre medicamentos y dispositivos, documentos del estudio
Estudia un producto farmacéutico regulado por la FDA de EE. UU.
Estudia un producto de dispositivo regulado por la FDA de EE. UU.
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