RESCUE - Effect of supplemental hydrocortisone during stress in prednisolone-induced adrenal insufficiency; A multicentre, randomised, double blinded, placebo-controlled clinical trial on health-related quality of life in patients with polymyalgia rheumatica/giant cell arteritis receiving ongoing low-dose prednisolone treatment.
试验速览
- 阶段
- 4 期
- 状态
- 招募中
- 入组人数
- 345
- 试验地点
- 3
- 主要终点
- Ecological momentary assessments (EMA) of the Multidimensional Fatigue Inventory (MFI-20), the General Fatigue scale, in situations of stress (Stress EMA). Details: EMA reporting will be done using a study smartphone applica-tion. When patients report stress, the app prompts participants to answer the four momentary MFI-20 General Fatigue questions five time daily at semi ran-domized timepoints for three days. A paper version is available for patients who cannot use a smartphone.
研究概览
简要总结
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 (PMR) and/or giant cell arteritis (GCA) diagnosed with glucocorticoid-induced adrenal insufficiency while on ongioing low-dose prednisolone treatment. The main emphasis is on fatigue (primary outcome) and daily variation hereof during periods of stress.
入排标准
- 年龄范围
- 18 years 至 65+ years（18-64 Years, 65+ Years）
- 接受健康志愿者
- 否
入选标准
- •Age ≥ 50 years
- •Women must be postmenopausal
- •A diagnosis of polymyalgia rheumatica (PMR), giant cell arteritis (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.
排除标准
- •Known primary or secondary adrenal insufficiency
- •Known Cushing’ s Syndrome
- •Known allergy towards study medication ingredients
- •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).
- •Alcohol consumption >21 units per week
- •Planned major surgery during the study period at study entry.
- •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).
- •Inability to provide written informed consent.
结局指标
主要结局
Ecological momentary assessments (EMA) of the Multidimensional Fatigue Inventory (MFI-20), the General Fatigue scale, in situations of stress (Stress EMA). Details: EMA reporting will be done using a study smartphone applica-tion. When patients report stress, the app prompts participants to answer the four momentary MFI-20 General Fatigue questions five time daily at semi ran-domized timepoints for three days. A paper version is available for patients who cannot use a smartphone.
Ecological momentary assessments (EMA) of the Multidimensional Fatigue Inventory (MFI-20), the General Fatigue scale, in situations of stress (Stress EMA). Details: EMA reporting will be done using a study smartphone applica-tion. When patients report stress, the app prompts participants to answer the four momentary MFI-20 General Fatigue questions five time daily at semi ran-domized timepoints for three days. A paper version is available for patients who cannot use a smartphone.
次要结局
- Key secondary outcome: EMA version of the MFI-20 General Fatigue scale at baseline (baseline EMA) and at fixed timepoints monthly (unstressed EMA)
- Key secondary outcome: SF-36v2 questionnaire
- 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.
- Key secondary outcome: AddiQol-30 questionnaire
- 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.
- Key secondary outcome: Number of ‘sick days’
- 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).
- Safety outcomes: Adrenal insufficiency: Incidence rate and grade of adrenal crises; Number of hospitalisations
- 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.
- Safety outcome: Exogenous Cushing’s Syndrome - Bone quality: Bone markers in blood and urine
- 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.
- Safety outcome: Exogenous Cushing’s Syndrome - Patient reported symptoms: CushingQol questionnaire; Single item Sleep Quality Scale (SQS) questionnaire
- Exploratory outcome: PMR/GCA treatment characteristics: Number of PMR/GCA disease flare up/relapse, and disease activity of the PMR/GCA.
- 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).
研究者
MD PhD Stina Willemoes Borresen (study coordinator) & MD DMSc Ulla Feldt-Rasmussen (sponsor)
Scientific
Rigshospitalet