Treating side effects of steroid medicatio

Phase 1

• Conditions: Adverse effects of prescribed glucocorticoid therapy; MedDRA version: 19.0Level: LLTClassification code 10068501Term: Cushing's syndrome, steroid-inducedSystem Organ Class: 100000004860; Therapeutic area: Body processes [G] - Metabolic Phenomena [G03]

• Registration Number: EUCTR2016-003060-40-GB
• Lead Sponsor: niversity of Oxford, Clinical Trials and Research Governance

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2016-12-22
• Last Update Posted: 27 July 2020

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: Male
• Target Recruitment: 32

Inclusion Criteria

Male volunteers without diabetes (HbA1C < 48mmol/mol at screening)
•BMI 20-30kg/m2
•Age 18-60years
•Individuals (identified from Oxford Biobank) with fasting insulin and / or glucose and / or insulin resistance as measured by HOMA IR in the 40th-60th percentile
•BP<160/100mmHg with stable antihypertensive therapy for >3months
•Stable lipid lowering therapy for >3 months
•No contraindications to AZD4017 or prednisolone treatment
•Study participants who are sexually active with a female partner of childbearing potential must be surgically sterilised, practicing abstinence, or agree, along with their partners, to use two forms of highly effective methods of birth control (i.e. condom plus another highly effective method defined below), and not rely on barrier methods and spermicide alone, from the time of screening until 1 week after final dose of study drug. Male study participants must also not donate sperm from the time of screening until 1 week after final dose of study drug.

Highly effective methods of contraception are defined as combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (either oral, intravaginal or transdermal), progestogen-only hormonal contraception associated with inhibition of ovulation (either oral [specifically Cerazette], injectable or implantable), intrauterine device (IUD), intrauterine hormone-releasing system (IUS), bilateral tubal occlusion, vasectomised partner or sexual abstinence.

Are the trial subjects under 18? no
Number of subjects for this age range: 0
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 32
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range 0

Exclusion Criteria

•Age <18 or >60years
•Body mass index <20 or >30kg/m2
•A diagnosis of diabetes (type 1 or type 2)
•A blood haemoglobin <120mg/dL
•Haemorrhagic disorders
•Anticoagulant treatment
•Renal impairment with eGFR <60ml/min
•Abnormal liver chemistry with AST, ALT and/or GGT and/or bilirubin >ULN
•Glucocorticoid therapy (including inhaled, topical or oral) within the last 6 months
•Concomitant anti-inflammatory medication including NSAIDs, disease modifying anti-rheumatic drugs (DMARDs) / steroid-sparing medications (e.g. methotrexate, sulphasalzine, hydroxychloroquine, azathioprine, leflunamide, biologics [anti-TNFa, IL-1ra])
•Any medical condition in the opinion of the investigator that might impact upon safety or validity of the results – recent (within 2 weeks) or active infection, known liver disease, known thyroid disease, active malignancy, existing inflammatory condition (e.g. inflammatory athropathy, inflammatory bowel disease, autoimmune disease, connective tissue disease)
•Participation in another IMP trial / study within the past 6 months

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: Our main research objectives is…<br><br>1. To demonstrate the beneficial effect of the selective 11ß-HSD1 inhibitor, AZD4017, upon the prednisolone-induced deterioration in glucose uptake into skeletal muscle and glucose production by the liver.<br><br><br>;Secondary Objective: Our secondary research objectives are...<br><br>1.To determine the impact of AZD4017 on the anti-inflammatory actions of Prednisolone. <br><br>2.To identify the tissue-specific (skeletal muscle, adipose) mechanisms underpinning the response to Prednisolone therapy administered in conjunction with AZD4017.;Primary end point(s): The change in glucose disposal as measured during a hyperinsulinaemic euglycaemic clamp.<br><br>;Timepoint(s) of evaluation of this end point: Investigations will be performed at baseline and after 7 days of treatment