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

21. marts 2019 opdateret af: 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.

Studieoversigt

Status

Afsluttet

Betingelser

Intervention / Behandling

Detaljeret beskrivelse

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.

Undersøgelsestype

Interventionel

Tilmelding (Faktiske)

28

Fase

  • Fase 2

Kontakter og lokationer

Dette afsnit indeholder kontaktoplysninger for dem, der udfører undersøgelsen, og oplysninger om, hvor denne undersøgelse udføres.

Studiesteder

Deltagelseskriterier

Forskere leder efter personer, der passer til en bestemt beskrivelse, kaldet berettigelseskriterier. Nogle eksempler på disse kriterier er en persons generelle helbredstilstand eller tidligere behandlinger.

Berettigelseskriterier

Aldre berettiget til at studere

18 år og ældre (Voksen, Ældre voksen)

Tager imod sunde frivillige

Ingen

Køn, der er berettiget til at studere

Alle

Beskrivelse

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

Studieplan

Dette afsnit indeholder detaljer om studieplanen, herunder hvordan undersøgelsen er designet, og hvad undersøgelsen måler.

Hvordan er undersøgelsen tilrettelagt?

Design detaljer

  • Primært formål: Behandling
  • Tildeling: Randomiseret
  • Interventionel model: Parallel tildeling
  • Maskning: Firedobbelt

Våben og indgreb

Deltagergruppe / Arm
Intervention / Behandling
Aktiv komparator: AZD4017
400mg oral AZD4017 twice daily for 35 days
Medicin: 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.
Placebo komparator: Placebo
A placebo tablet containing microcrystalline cellulose and sodium stearyl fumarate to match the active tablets in size, shape and colour.
Medicin: Placebo
Matchende placebo

Hvad måler undersøgelsen?

Primære resultatmål

Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
Skin 11β-HSD1 activity
Tidsramme: Change between day 0 and day 28
Enzyme activity radioassay to evaluate AZD4107 efficacy in skin
Change between day 0 and day 28

Sekundære resultatmål

Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
Urinary cortisol / cortisone metabolites
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: Day 42
Adverse Event-related participant withdrawals to evaluate safety
Day 42
Body mass index
Tidsramme: Change between day 0 and day 35
Body mass index to evaluate safety
Change between day 0 and day 35
Waist-hip ratio
Tidsramme: Change between day 0 and day 35
Waist-hip ratio to evaluate safety
Change between day 0 and day 35
Blood pressure (sphygmomanometer)
Tidsramme: Change between day 0 and day 35
Blood pressure to evaluate safety
Change between day 0 and day 35
Sudomotor function
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: Change between day 0 and day 28
For skin function
Change between day 0 and day 28

Samarbejdspartnere og efterforskere

Det er her, du vil finde personer og organisationer, der er involveret i denne undersøgelse.

Sponsor

University of Leeds

Datoer for undersøgelser

Disse datoer sporer fremskridtene for indsendelser af undersøgelsesrekord og resumeresultater til ClinicalTrials.gov. Studieregistreringer og rapporterede resultater gennemgås af National Library of Medicine (NLM) for at sikre, at de opfylder specifikke kvalitetskontrolstandarder, før de offentliggøres på den offentlige hjemmeside.

Studer store datoer

Studiestart (Faktiske)

10. april 2018

Primær færdiggørelse (Faktiske)

27. februar 2019

Studieafslutning (Faktiske)

13. marts 2019

Datoer for studieregistrering

Først indsendt

5. oktober 2017

Først indsendt, der opfyldte QC-kriterier

17. oktober 2017

Først opslået (Faktiske)

18. oktober 2017

Opdateringer af undersøgelsesjournaler

Sidste opdatering sendt (Faktiske)

22. marts 2019

Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier

21. marts 2019

Sidst verificeret

1. marts 2019

Mere information

Begreber relateret til denne undersøgelse

Nøgleord

Yderligere relevante MeSH-vilkår

Andre undersøgelses-id-numre

  • ED17/93260

Lægemiddel- og udstyrsoplysninger, undersøgelsesdokumenter

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