Diabetes Mellitus, Type 2Phase 2GC-SHealDNCT03313297
Glucocorticoids and Skin Healing in Diabetes (GC-SHealD)
A Phase 2 study testing AZD4017 in people with Diabetes Mellitus, Type 2, run by University of Leeds at 1 site in United Kingdom.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Diabetes Mellitus, Type 2
- What is being tested?
- AZD4017
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 28 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 10 Apr 2018to 13 Mar 2019
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 18Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
About this study
Official title: 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.
Read the detailed description
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.
- Conditions
- Diabetes Mellitus, Type 2
- Being tested
- AZD4017, Placebo
- Keywords
- skin, wound healing, 11 beta-hydroxysteroid dehydrogenase type 1
- Medical subject headings
- Diabetes Mellitus, Type 2
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AZD4017Drug
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.
PlaceboDrug
Matching placebo
| Study group | Role | What they receive |
|---|---|---|
| AZD4017 | Active comparator | 400mg oral AZD4017 twice daily for 35 days Receives: 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. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Skin 11β-HSD1 activity
Enzyme activity radioassay to evaluate AZD4107 efficacy in skin
Measured: Change between day 0 and day 28
Secondary outcomes (17)
Urinary cortisol / cortisone metabolites
Urine samples for tetrahydrocortisol / tetrahydrocortisone metabolite ratios to evaluate systemic AZD4107 efficacy
Measured: Change between day 0 and day 35
AZD4017 in plasma
Quantification of AZD4017 concentration in plasma to evaluate systemic AZD4107 exposure
Measured: Change between day 0 and day 28
AZD4017 in skin
Quantification of AZD4017 concentration in plasma to evaluate skin AZD4107 exposure
Measured: Change between day 0 and day 28
Discontinuation due to Adverse Event
Adverse Event-related participant withdrawals to evaluate safety
Measured: Day 42
Body mass index
Body mass index to evaluate safety
Measured: Change between day 0 and day 35
Waist-hip ratio
Waist-hip ratio to evaluate safety
Measured: Change between day 0 and day 35
Blood pressure (sphygmomanometer)
Blood pressure to evaluate safety
Measured: Change between day 0 and day 35
Sudomotor function
Conducted with a Sudoscan device to measure c-fiber innervation in hands and feet for skin function
Measured: Change between day 0 and day 35
Skin hydration
Conducted with a Corneometer device to measure skin water content for skin function
Measured: Change between day 0 and day 35
Epidermal barrier function
Conducted with a Tewameter device to measure skin trans-epidermal water loss for skin function
Measured: Change between day 0 and day 35
Epidermal barrier integrity
Conducted by tape tripping to a pre-determined trans-epidermal water loss rate for skin function
Measured: Change between day 0 and day 28
Skin thickness
Conducted by Optical Coherence Tomography imaging for skin function
Measured: Change between day 0 and day 35
Wound healing
Conducted by Optical Coherence Tomography imaging for skin function
Measured: Change between day 0 and day 2
Wound healing
Conducted by Optical Coherence Tomography imaging for skin function
Measured: Change between day 0 and day 7
Wound healing
Conducted by Optical Coherence Tomography imaging for skin function
Measured: Change between day 28 and day 30
Wound healing
Conducted by Optical Coherence Tomography imaging for skin function
Measured: Change between day 28 and day 35
Skin RNA-seq gene expression profiling
For skin function
Measured: Change between day 0 and day 28
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Oct 2017
- Study start10 Apr 2018
- Primary completion27 Feb 2019
- Study completion13 Mar 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Diabetes Mellitus, Type 2Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Double-blind, randomised, parallel group, placebo-controlled phase II pilot trial
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 28 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Leeds
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Ana Tiganescu, PhD, University of Leeds
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03313297
- Sponsor's protocol ID
- ED17/93260
- Acronym
- GC-SHealD
- Status last verified
- Mar 2019
- First submitted
- 5 Oct 2017
- Last updated
- 22 Mar 2019
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 22 Mar 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT03313297
- Acronym / sponsor ID
- GC-SHealD / ED17/93260
- Conditions
- Diabetes Mellitus, Type 2
- Keywords
- skin, wound healing, 11 beta-hydroxysteroid dehydrogenase type 1
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 28 participants (actual)
- Lead sponsor
- University of LeedsUniversity, hospital or other
- Study start
- 10 Apr 2018 (actual)
- Primary completion
- 27 Feb 2019 (actual)
- Study completion
- 13 Mar 2019 (actual)
- First posted
- 18 Oct 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- Double-blind, randomised, parallel group, placebo-controlled phase II pilot trial
| Arm | Type | Receives |
|---|---|---|
| AZD4017 | Active comparator | Drug: AZD4017400mg oral AZD4017 twice daily for 35 days |
| Placebo | Placebo comparator | Drug: PlaceboA placebo tablet containing microcrystalline cellulose and sodium stearyl fumarate to match the active tablets in size, shape and colour. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- 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
Key exclusion criteria (18 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AZD4017AZD4017 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. | Drug | AZD4017 |
| PlaceboMatching placebo | Drug | Placebo |
Primary outcome
Skin 11β-HSD1 activity
Time frame: Change between day 0 and day 28
Enzyme activity radioassay to evaluate AZD4107 efficacy in skin
17 secondary outcomes
Urinary cortisol / cortisone metabolites
Time frame: Change between day 0 and day 35
AZD4017 in plasma
Time frame: Change between day 0 and day 28
AZD4017 in skin
Time frame: Change between day 0 and day 28
Discontinuation due to Adverse Event
Time frame: Day 42
Body mass index
Time frame: Change between day 0 and day 35
Waist-hip ratio
Time frame: Change between day 0 and day 35
Blood pressure (sphygmomanometer)
Time frame: Change between day 0 and day 35
Sudomotor function
Time frame: Change between day 0 and day 35
Skin hydration
Time frame: Change between day 0 and day 35
Epidermal barrier function
Time frame: Change between day 0 and day 35
Epidermal barrier integrity
Time frame: Change between day 0 and day 28
Skin thickness
Time frame: Change between day 0 and day 35
Wound healing
Time frame: Change between day 0 and day 2
Wound healing
Time frame: Change between day 0 and day 7
Wound healing
Time frame: Change between day 28 and day 30
Wound healing
Time frame: Change between day 28 and day 35
Skin RNA-seq gene expression profiling
Time frame: Change between day 0 and day 28
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Mar 2019.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing AZD4017 in people with Diabetes Mellitus, Type 2, run by University of Leeds at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 22 Mar 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Skin 11β-HSD1 activity (time frame: Change between day 0 and day 28). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Mar 2019.