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.
調査の概要
詳細な説明
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
- 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.
研究の種類
介入
入学 (実際)
28
段階
- フェーズ2
連絡先と場所
このセクションには、調査を実施する担当者の連絡先の詳細と、この調査が実施されている場所に関する情報が記載されています。
研究場所
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Leeds、イギリス、LS9 7TF
- Leeds Teaching Hospitals Trust
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参加基準
研究者は、適格基準と呼ばれる特定の説明に適合する人を探します。これらの基準のいくつかの例は、人の一般的な健康状態または以前の治療です。
適格基準
就学可能な年齢
18年歳以上 (大人、高齢者)
健康ボランティアの受け入れ
いいえ
受講資格のある性別
全て
説明
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
研究計画
このセクションでは、研究がどのように設計され、研究が何を測定しているかなど、研究計画の詳細を提供します。
研究はどのように設計されていますか？
デザインの詳細
- 主な目的：処理
- 割り当て：ランダム化
- 介入モデル：並列代入
- マスキング：4倍
武器と介入
参加者グループ / アーム |
介入・治療 |
|---|---|
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アクティブコンパレータ：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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プラセボコンパレーター：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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一致するプラセボ
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この研究は何を測定していますか？
主要な結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
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Skin 11β-HSD1 activity
時間枠：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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二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
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Urinary cortisol / cortisone metabolites
時間枠：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
時間枠：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
時間枠：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
時間枠：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
時間枠：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
時間枠：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)
時間枠：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
時間枠：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
時間枠：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
時間枠：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
時間枠：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
時間枠：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
時間枠：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
時間枠：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
時間枠：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
時間枠：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
時間枠：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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協力者と研究者
ここでは、この調査に関係する人々や組織を見つけることができます。
スポンサー
研究記録日
これらの日付は、ClinicalTrials.gov への研究記録と要約結果の提出の進捗状況を追跡します。研究記録と報告された結果は、国立医学図書館 (NLM) によって審査され、公開 Web サイトに掲載される前に、特定の品質管理基準を満たしていることが確認されます。
主要日程の研究
研究開始 (実際)
2018年4月10日
一次修了 (実際)
2019年2月27日
研究の完了 (実際)
2019年3月13日
試験登録日
最初に提出
2017年10月5日
QC基準を満たした最初の提出物
2017年10月17日
最初の投稿 (実際)
2017年10月18日
学習記録の更新
投稿された最後の更新 (実際)
2019年3月22日
QC基準を満たした最後の更新が送信されました
2019年3月21日
最終確認日
2019年3月1日
詳しくは
この情報は、Web サイト clinicaltrials.gov から変更なしで直接取得したものです。研究の詳細を変更、削除、または更新するリクエストがある場合は、register@clinicaltrials.gov。 までご連絡ください。 clinicaltrials.gov に変更が加えられるとすぐに、ウェブサイトでも自動的に更新されます。