Glucocorticoids and Skin Healing in Diabetes (GC-SHealD)

NCT03313297 | Completed Phase 2 DMC

• 1 other identifier: ED17/93260
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Diabetes Mellitus, Type 2

Keywords

skin; wound healing; 11 beta-hydroxysteroid dehydrogenase type 1

Outcome Measures

Primary Outcomes (1)

• Skin 11β-HSD1 activity

  Enzyme activity radioassay to evaluate AZD4107 efficacy in skin

  Change between day 0 and day 28

Secondary Outcomes (17)

• 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

• Body mass index

  Change between day 0 and day 35

Study Arms (2)

AZD4017

ACTIVE COMPARATOR

400mg oral AZD4017 twice daily for 35 days

Drug: AZD4017

Placebo

PLACEBO COMPARATOR

A placebo tablet containing microcrystalline cellulose and sodium stearyl fumarate to match the active tablets in size, shape and colour.

Drug: Placebo

Interventions

AZD4017 DRUG

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.

AZD4017

Placebo DRUG

Matching placebo

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• University of Leeds: lead

Study Sites (1)

Leeds Teaching Hospitals Trust

Leeds, LS9 7TF, United Kingdom

Location

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Interventions

2-(1-(5-(cyclohexylcarbamoyl)-6-propylsulfanylpyridin-2-yl)-3-piperidyl)acetic acid

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: 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.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Scientific Lead

Model Details: Double-blind, randomised, parallel group, placebo-controlled phase II pilot trial

Study Record Dates

• First Submitted: October 5, 2017
• First Posted: October 18, 2017
• Study Start: April 10, 2018
• Primary Completion: February 27, 2019
• Study Completion: March 13, 2019
• Last Updated: March 22, 2019

Record last verified: 2019-03

Locations

GB (1)