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Glucocorticoids and Skin Healing in Diabetes (GC-SHealD) (GC-SHealD)

2019年3月21日 更新者：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.

研究概览

地位

完全的

条件

干预/治疗

详细说明

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

  1. Oral AZD4017 inhibits 11β-HSD1 activity in skin
  2. AZD4017 is safe and well-tolerated in patient with T2DM
  3. Oral AZD4017 regulates skin function
  4. 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.

研究类型

介入性

注册 (实际的)

28

阶段

  • 阶段2

联系人和位置

本节提供了进行研究的人员的详细联系信息，以及有关进行该研究的地点的信息。

学习地点

  • 英国
      • Leeds、英国、LS9 7TF
        • Leeds Teaching Hospitals Trust

参与标准

研究人员寻找符合特定描述的人，称为资格标准。这些标准的一些例子是一个人的一般健康状况或先前的治疗。

资格标准

适合学习的年龄

18年 及以上 (成人、年长者)

接受健康志愿者

不

有资格学习的性别

全部

描述

Inclusion Criteria:

  1. Able and willing to consent
  2. Type 2 diabetes with HbA1c ≤11% (≤97 mmol/mol) at screening while taking standard therapy at a stable dose for ≥10 weeks

Exclusion Criteria:

  1. Women of child-bearing potential
  2. Active leg/foot ulceration
  3. Clinically relevant acute electrocardiogram anomalies
  4. Uncontrolled hypertension
  5. Endocrine disorder (other than type 2 diabetes ), including type 1 or secondary diabetes (except treated hypothyroidism)
  6. Gilbert's disease
  7. Alanine aminotransferase and/or aspartate aminotransferase and/or alkaline phosphatase >1.5x upper limit of normal (ULN)
  8. Bilirubin >1.5x ULN
  9. Estimated glomerular filtration rate <45 ml/min/m2
  10. Creatine kinase >2x ULN
  11. Drug abuse within the last year
  12. Any glucocorticoid treatment within 3 months of screening
  13. Anti-coagulant medication
  14. Probenecid therapy
  15. Medical/surgical procedure or trauma during drug administration or one week after drug cessation (excluding skin biopsies)
  16. Involvement in trial planning and/or conduct
  17. Participation in other clinical study within 1 month
  18. Deemed inappropriate to participate by the trial team

学习计划

本节提供研究计划的详细信息，包括研究的设计方式和研究的衡量标准。

研究是如何设计的？

设计细节

  • 主要用途：治疗
  • 分配：随机化
  • 介入模型：并行分配
  • 屏蔽：四人间

武器和干预

参与者组/臂
干预/治疗
有源比较器：AZD4017
400mg oral AZD4017 twice daily for 35 days
药品：AZD4017
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.
安慰剂比较：Placebo
A placebo tablet containing microcrystalline cellulose and sodium stearyl fumarate to match the active tablets in size, shape and colour.
药品：安慰剂
匹配安慰剂

研究衡量的是什么？

主要结果指标

结果测量
措施说明
大体时间
Skin 11β-HSD1 activity
大体时间：Change between day 0 and day 28
Enzyme activity radioassay to evaluate AZD4107 efficacy in skin
Change between day 0 and day 28

次要结果测量

结果测量
措施说明
大体时间
Urinary cortisol / cortisone metabolites
大体时间：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
大体时间：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
大体时间：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
大体时间：Day 42
Adverse Event-related participant withdrawals to evaluate safety
Day 42
Body mass index
大体时间：Change between day 0 and day 35
Body mass index to evaluate safety
Change between day 0 and day 35
Waist-hip ratio
大体时间：Change between day 0 and day 35
Waist-hip ratio to evaluate safety
Change between day 0 and day 35
Blood pressure (sphygmomanometer)
大体时间：Change between day 0 and day 35
Blood pressure to evaluate safety
Change between day 0 and day 35
Sudomotor function
大体时间：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
大体时间：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
大体时间：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
大体时间：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
大体时间：Change between day 0 and day 35
Conducted by Optical Coherence Tomography imaging for skin function
Change between day 0 and day 35
Wound healing
大体时间：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
大体时间：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
大体时间：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
大体时间：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
大体时间：Change between day 0 and day 28
For skin function
Change between day 0 and day 28

合作者和调查者

在这里您可以找到参与这项研究的人员和组织。

赞助

University of Leeds

研究记录日期

这些日期跟踪向 ClinicalTrials.gov 提交研究记录和摘要结果的进度。研究记录和报告的结果由国家医学图书馆 (NLM) 审查，以确保它们在发布到公共网站之前符合特定的质量控制标准。

研究主要日期

学习开始 (实际的)

2018年4月10日

初级完成 (实际的)

2019年2月27日

研究完成 (实际的)

2019年3月13日

研究注册日期

首次提交

2017年10月5日

首先提交符合 QC 标准的

2017年10月17日

首次发布 (实际的)

2017年10月18日

研究记录更新

最后更新发布 (实际的)

2019年3月22日

上次提交的符合 QC 标准的更新

2019年3月21日

最后验证

2019年3月1日

更多信息

与本研究相关的术语

关键字

其他相关的 MeSH 术语

其他研究编号

  • ED17/93260

药物和器械信息、研究文件

研究美国 FDA 监管的药品

不

研究美国 FDA 监管的设备产品

不

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