Hydrocortisone for Glucocorticoid-induced adrenal insufficiency | Polymyalgia rheumatica | Giant cell arteritis

Inclusion criteria

• {"criterion_text":"- Age ≥ 50 years\n- Women must be postmenopausal\n- A diagnosis of polymyalgia rheumatica (PMR), giant cell arteritis (GCA), or both conditions combined\n- Treatment with prednisolone ≥12 weeks\n- 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."}

Exclusion criteria

• {"criterion_text":"- Known primary or secondary adrenal insufficiency\n- Known Cushing’\ts Syndrome\n- Known allergy towards study medication ingredients\n- Severe comorbidity defined as: Heart failure (New York Heart Association class IV); Kidney failure with an estimated glomerular filtration rate <30 mL/min (Chronic kidney disease stage 4-5); Liver disease in the form of cirrhosis; Active cancer; Known severe immune deficiency; A history of psychiatric disease requiring treatment by a psychiatric department (for affective disorders only if within the last year before study entry).\n- Alcohol consumption >21 units per week\n- Planned major surgery during the study period at study entry.\n- Use of drugs that interfere with cortisol metabolism/measurements defined as: Systemic oestrogen treatment (discontinued < 1 month before inclusion); Treatment with strong CYP3A4 inhibitors or inducers (defined in Table 2 in the study protocol); 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).\n- Inability to provide written informed consent."}

Primary endpoints

• {"endpoint_text":"- Ecological momentary assessments (EMA) of the Multidimensional Fatigue Inventory (MFI-20), the General Fatigue scale, in situations of stress (Stress EMA).","definition_or_measurement_approach":"EMA reporting will be done using a study smartphone application. When patients report stress, the app prompts participants to answer the four momentary MFI-20 General Fatigue questions five time daily at semi randomized timepoints for three days. A paper version is available for patients who cannot use a smartphone."}

Secondary endpoints

• {"endpoint_text":"- Key secondary outcome: EMA version of the MFI-20 General Fatigue scale at baseline (baseline EMA) and at fixed timepoints monthly (unstressed EMA)","definition_or_measurement_approach":""}
• {"endpoint_text":"- Key secondary outcome: SF-36v2 questionnaire","definition_or_measurement_approach":""}
• {"endpoint_text":"- Key secondary outcome: Daily ‘end-of-day’ smartphone app facilitated patient reported symptoms of adrenal insufficiency and intercurrent illness and stress. The questions about symptoms originate from the Danish version of the PRO-CTCAE questionnaire.","definition_or_measurement_approach":""}
• {"endpoint_text":"- Key secondary outcome: AddiQol-30 questionnaire","definition_or_measurement_approach":""}
• {"endpoint_text":"- Key secondary outcome: 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.","definition_or_measurement_approach":""}
• {"endpoint_text":"- Key secondary outcome: Number of ‘sick days’","definition_or_measurement_approach":""}
• {"endpoint_text":"- Key secondary outcome: ACTH test results depending on the length of the prednisolon pause: ACTH test results (basal and stimulated plasma cortisol) after 0, 1, or 2 days prednisolone pause; Prednisolone cross reactivity in Roche Elecsys cortisol II immunoassay in plasma 2 hours, 4 hours, 1 day and 2 days after last prednisolone intake; ACTH concentrations (central HPA axis recovery).","definition_or_measurement_approach":""}
• {"endpoint_text":"- Safety outcomes: Adrenal insufficiency: Incidence rate and grade of adrenal crises; Number of hospitalisations","definition_or_measurement_approach":""}
• {"endpoint_text":"- Safety outcome: Exogenous Cushing’s Syndrome - Body composition and muscle strength: Dual-energy X-ray absorptiometry (DXA) scan (fat percentage, body composition, bone mineral density); Waist- and hip circumference, weight, height, body mass index (BMI); Timed up and go; Handgrip strength; Short Physical Performance Battery and chair rising test.","definition_or_measurement_approach":""}
• {"endpoint_text":"- Safety outcome: Exogenous Cushing’s Syndrome - Bone quality: Bone markers in blood and urine","definition_or_measurement_approach":""}
• {"endpoint_text":"- Safety outcome: Exogenous Cushing’s Syndrome - Metabolic and cardiovascular risk: Automated office blood pressure; Coagulation and Inflammation markers in blood; Metabolic and cardiovascular markers in blood and urine.","definition_or_measurement_approach":""}
• {"endpoint_text":"- Safety outcome: Exogenous Cushing’s Syndrome - Patient reported symptoms: CushingQol questionnaire; Single item Sleep Quality Scale (SQS) questionnaire","definition_or_measurement_approach":""}

Other endpoints

• {"endpoint_text":"- Exploratory outcome: PMR/GCA treatment characteristics: Number of PMR/GCA disease flare up/relapse, and disease activity of the PMR/GCA.","definition_or_measurement_approach":""}
• {"endpoint_text":"- Exploratory outcome: Biological integrated cortisol status assessment: ACTH test for normalization of adrenal function; 24h urine; Salivary cortisol and cortisone during ACTH tests (determined by Roche immunoassay and LC-MS); Cortisol binding globulin (CBG) in plasma to calculate Free Cortisol Index (total P-cortisol concentration (nmol/l)/serum CBG (in mg/L). Circulating biomarkers of glucocorticoid effects and adverse effects (incl. glucocorticoid receptor gene polymorphisms).","definition_or_measurement_approach":""}

Denmark

Earliest CTIS Part Ii Submission Date

18-12-2024

Latest Decision Or Authorization Date

19-09-2025

Processing Time Days

275

Number Of Sites

3

Number Of Participants

345

Primary sponsor

Full Name

Rigshospitalet

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

Denmark

Third parties

• {"country":"Denmark","full_name":"Frederiksberg Hospital","duties_or_roles":"Sponsor duty code: 1","organisation_type":"Hospital/Clinic/Other health care facility"}