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
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 28
- 试验地点
- 1
- 主要终点
- Skin 11β-HSD1 activity
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
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.
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
AZD4017
400mg oral AZD4017 twice daily for 35 days
干预措施: AZD4017 (Drug)
Placebo
A placebo tablet containing microcrystalline cellulose and sodium stearyl fumarate to match the active tablets in size, shape and colour.
干预措施: Placebo (Drug)
结局指标
主要结局
Skin 11β-HSD1 activity
时间窗: Change between day 0 and day 28
Enzyme activity radioassay to evaluate AZD4107 efficacy in skin
次要结局
- Urinary cortisol / cortisone metabolites(Change between day 0 and day 35)
- AZD4017 in plasma(Change between day 0 and day 28)
- AZD4017 in skin(Change between day 0 and day 28)
- Discontinuation due to Adverse Event(Day 42)
- Sudomotor function(Change between day 0 and day 35)
- Waist-hip ratio(Change between day 0 and day 35)
- Body mass index(Change between day 0 and day 35)
- Blood pressure (sphygmomanometer)(Change between day 0 and day 35)
- Skin hydration(Change between day 0 and day 35)
- Epidermal barrier function(Change between day 0 and day 35)
- Epidermal barrier integrity(Change between day 0 and day 28)
- Skin thickness(Change between day 0 and day 35)
- Wound healing(Change between day 28 and day 35)
- Skin RNA-seq gene expression profiling(Change between day 0 and day 28)
研究者
Ana Tiganescu, PhD
Scientific Lead
University of Leeds