Glucocorticoid-induced adrenal insufficiency MedDRA version: 20.0 Level: LLT Classification code 10001369 Term: Adrenal insufficiency NOS System Organ Class: 100000004860
Conditions
Interventions
Trade Name: Hydrokortison orion
Product Name: hydrokortison
Product Code: H02AB09
Pharmaceutical Form: Tablet
INN or Proposed INN: hydrocortisone
Other descriptive name: HYDROCORTISONE
Concentration
Sponsors
Copenhagen University Hospital Rigshospitalet
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Age = 50 years • Women must be postmenopausal (FSH is measured at the screening visit) • A diagnosis of PMR/GCA, or both conditions combined. • Treatment with prednisolone =12 weeks • Ongoing prednisolone treatment, with current daily prednisolone dose > 0 mg and =5 mg. The dose must have been =5 mg for minimum 2 weeks at the time of the screening visit. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 162 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 163
Exclusion criteria
Exclusion criteria: • Known primary or secondary adrenal insufficiency • Known Cushing’ s Syndrome • Known allergy towards study medication ingredients • Severe comorbidity (Heart failure (New York Heart Association class IV); Kidney failure with an estimated glomerular filtration rate 21 units per week • Planned major surgery during the study period at study entry. • Use of drugs that interfere with cortisol metabolism/measurements (Systemic oestrogen treatment (discontinued < 1 month before inclusion); Treatment with strong CYP3A4 inhibitors or inducers; Use of other glucocorticoid formulations: Inhaled corticosteroids, intraarticular or intramuscular injections, steroid creams European steroid group IV-V used in the genital area. Permitted glucocorticoid formulations: Eye-drops, nasal spray, glucocorticoid creams European steroid group I-III, and European steroid group IV-V used in the non-genital area only. • Inability to provide written informed consent.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: In this double-blinded randomised placebo-controlled clinical trial, the aim is to determine the effect of supplemental hydrocortisone compared with placebo during mild to moderate physical or mental stress on health related quality of life in patients with polymyalgia rheumatica/giant cell arteritis (PMR/GCA) on ongioing low-dose prednisolone diagnosed with glucocorticoid-induced adrenal insufficiency. The main emphasis is on fatigue (primary outcome) and daily variation hereof during periods of stress.;Secondary Objective: Key secondary aims are • to determine the association between adrenal function and HRQoL at baseline • to determine the effect of hydrocortisone stress doses not only in situations of stress, but for general daily symptom reporting and generic and disease specific HRQoL reported with 4 weeks reference periods. • To determine the association between HRQoL and the severity of glucocorticoid-induced adrenal insufficiency (e.g. mild, moderate and severe) i) at baseline and ii) in patients receiving hydrocortisone stress doses compared with placebo. • To determine the effect of treating adrenal insufficiency with hydrocortisone stress doses on the ease of tapering prednisolone treatment for PMR/GCA. • To determine the effect of stress doses on patient safety regarding hypo- and hypercortisolism (adrenal crises, sick days and hospitalisations, and exogenous cushingoid signs and symptoms) Further aims are to investigate biomarkers of glucocorticoid sensitivity and action ;Primary end point(s): Symptoms of adrenal insufficiency: daily variation of fatigue (Ecological Momentary Assessments (EMA) of the Multidimensional Fatigue Inventory 20 questions (MFI-20) General Fatigue scale);Timepoint(s) of evaluation of this end point: Days with ilness or stress | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Key secondary outcomes • SF-36, the Physical Health Component Summary • PRO-CTCAE symptoms fatigue, nausea and pain • AddiQol-30 • PMR/GCA treatment characteristics (duration of prednisolone tapering from 5 mg to complete withdrawal, accumulated dose of glucocorticoid treatment, duration of prednisolone treatment for PMR/GCA) • Number of ‘sick days’ Safety outcomes Adrenal insufficiency • Incidence rate and grade of adrenal crises • Number of hospitalisations Exogenous Cushing’s Syndrome • Body composition and muscle strength (Dual-energy X-ray absorptiometry (DXA) scan: fat percentage, body composition, bone mineral density, Waist, hip, weight, height, body mass index (BMI), Timed up and go, Handgrip strength, Short Physical Performance Battery and chair rising test • Bone quality (Bone markers in blood and urine) • Metabolic and cardiovascular risk (Automated office blood pressure, Coagulation and Inflammation markers in blood, Metabolic and cardiovascular markers in blood and urine) • Patient reported symptoms (CushingQol, Single item Sleep Quality Scale (SQS) Exploratory outcomes • Health-Related Quality of Life measured by SF-36 eight domain scores and Mental Health Component Summary • PMR/GCA treatment characteristics: Number of PMR/GCA disease flare up/relapse, and disease activity of the PMR/GCA. • Biological integrated cortisol status assessment (ACTH test for normalization of adrenal function, 24h urine, Salivary cortisol, Circulating biomarkers of glucocorticoid effects and adverse effects, P-cortisol after 24 hours prednisolone pause analysed with several methods);Timepoint(s) of evaluation of this end point: baseline, 3 months, 6 months | — |
Countries
Denmark
Contacts
Public ContactDepartment of Medical Endocrinology
Copenhagen University Hospital Rigshospitalet
Outcome results
None listed