A Phase 4 interventional study of Hydrocortisone and Placebo for hydrocortisone in Adrenal Insufficiency, Polymyalgia Rheumatica and Giant Cell Arteritis, sponsored by Marianne Christina Klose. Recruiting at 3 sites in Denmark. Open to participants aged 50 Years and older. Per ClinicalTrials.gov, last updated 2026-03-16.
Sponsored by Marianne Christina Klose · Phase 4, Interventional, and Treatment
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)/giant cell arteritis (GCA) on ongoing 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.
The study will include patients with PMR/GCA on ongoing prednisolone treatment in a low dose of > 0 mg/day and ≤5mg/day. Eligible patients will undergo a Synacthen® test and 250 patients with a stimulated cortisol level \<420 nmol/l (biochemical adrenal insufficiency) will be randomised to either placebo or hydrocortisone supplemental doses during stress. Patients will continue prednisolone treatment and tapering hereof according to current clinical guidelines for PMR/GCA and add supplemental hydrocortisone/placebo in situations of stress according to study protocol. In situations of severe stress (potential adrenal crisis) patients will receive open label hydrocortisone treatment according to routine clinical care. The duration of RESCUE is 6 months but stops earlier if the patient stops prednisolone treatment earlier. In case of a flare of PMR/GCA during the study where prednisolone is increased to >5mg/day for e.g. 5 weeks the study is prolonged accordingly 5 weeks.
Ninety-five patients with stimulated cortisol ≥420 nmol/l (normal adrenal function) will be used as a reference group. The participants will undergo screening and baseline examinations, 3 month's reporting of HRQoL, and with patient consent follow-up through medical records on prednisolone treatment characteristics, and number of hospitalisations.
136 studies on the registry are indexed under Adrenal Insufficiency; 27 are open to participants now.
This study's planned enrollment of 250 is above the median of 44 across 71 interventional studies indexed under Adrenal Insufficiency.
Browse Adrenal Insufficiency studies →This is the only study on the registry with Marianne Christina Klose as lead sponsor.
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Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Periods have stopped for good: usually no period for 12 months in a row without another medical reason, sometimes confirmed by a blood test (FSH).
The New York Heart Association’s four classes of how much heart failure limits physical activity.
Studies set their own limit — many outside heart failure leave out class III–IV, while heart failure studies may ask for a particular class. Check the class this study names.
GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².
Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.
CYP3A is a group of enzymes, mainly CYP3A4, in the liver and gut that break down many medicines. Some medicines, supplements and foods (grapefruit, St John’s wort) slow them down or speed them up, which changes how much of a study drug stays in the body.
Studies list them so they can be avoided or switched; bring a list of everything you take, including supplements.
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Postmenopausal
Periods have stopped for good: usually no period for 12 months in a row without another medical reason, sometimes confirmed by a blood test (FSH).
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
NYHA class (heart failure)
The New York Heart Association’s four classes of how much heart failure limits physical activity.
Studies set their own limit — many outside heart failure leave out class III–IV, while heart failure studies may ask for a particular class. Check the class this study names.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
GFR and eGFR (kidney filtering)
GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².
Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
CYP3A (CYP3A4) inhibitors and inducers
CYP3A is a group of enzymes, mainly CYP3A4, in the liver and gut that break down many medicines. Some medicines, supplements and foods (grapefruit, St John’s wort) slow them down or speed them up, which changes how much of a study drug stays in the body.
Studies list them so they can be avoided or switched; bring a list of everything you take, including supplements.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Corticosteroids (steroids)
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Patients with polymyalgia rheumatica/giant cell arteritis with glucocorticoid-induced adrenal insufficiency (Synacthen test response \<420 nmol/l) that are randomised to receive hydrocortisone
Drug: Hydrocortisone
Patients with polymyalgia rheumatica/giant cell arteritis with glucocorticoid-induced adrenal insufficiency (Synacthen test response \<420 nmol/l) that are randomised to receive placebo
Drug: Placebo for hydrocortisone
Patients with polymyalgia rheumatica/giant cell arteritis with normal adrenal function (Synacthen test response ≥420 nmol/l)
Patients are randomised to either placebo or hydrocortisone supplemental doses in situations of stress. Patients will continue prednisolone treatment and tapering hereof according to current clinical guidelines for PMR/GCA , prednisolone is not part of the intervention.
Patients are randomised to either placebo or hydrocortisone supplemental doses in situations of stress. Patients will continue prednisolone treatment and tapering hereof according to current clinical guidelines for PMR/GCA , prednisolone is not part of the intervention.
ecological momentary assessments (EMA) of the Multidimensional Fatigue Inventory (MFI-20) General Fatigue scale, adjusted for EMA
EMA in situations of stress. EMA reporting will be conducted electronically on a smartphone.
Time frame: In situations of stress, participants are asked to answer the EMA items 5 times daily at semi-randomised time points, for 3 days. Diurnal profiles are generated and one diurnal profile summarizes responses during the day across all 'sick-days'.
Daily 'end-of-day' app-facilitated patient reported outcome (PRO) assessments
Key secondary outcome - obtain information about intercurrent illness, injury, or stress, and symptoms of fatigue, nausea, and general malaise. The questions about symptoms originate from the Danish version of the PRO-CTCAE.
Time frame: Patients are asked daily throughout the study period as 'end-of-day' assessments.
SF-36
Key secondary outcome
Time frame: At baseline, 3 months and 6 months
AddiQol-30
Key secondary outcome
Time frame: At baseline, 3 months and 6 months
PMR/GCA treatment characteristics -accumulated glucocorticoid dose
Key secondary outcome. accumulated glucocorticoid dose
Time frame: Information from 6 months before baseline to end-of study
PMR/GCA treatment characteristics -prednisolone treatment duration
Key secondary outcome. Duration of prednisolone treatment, duration of prednisolone tapering (5 mg - 0 mg)
Time frame: Information from 6 months before baseline to end-of study
Number of 'sick days'
Key secondary outcome
Time frame: Throughout study period (6 months)
Incidens of adrenal crises and hospitalisations
Incidence rate of adrenal crises and hospitalisations
Time frame: Throughout study period (6 months)
Adrenal crises grading
Grade of adrenal crises.
Time frame: Throughout study period (6 months)
Body composition and muscle strength - DXA scan
Safety outcome for exogenous Cushing's Syndrome (Dual-energy X-ray absorptiometry (DXA) scan: fat percentage, body composition
Time frame: Baseline and 6 months
Body composition and muscle strength - Waist, hip, height
Safety outcome for exogenous Cushing's Syndrome (Waist, hip, height)
Time frame: Baseline and 6 months
Body composition and muscle strength -weight
Safety outcome for exogenous Cushing's Syndrome (weight)
Time frame: Baseline and 6 months
Body composition and muscle strength - body mass index (BMI)
Safety outcome for exogenous Cushing's Syndrome (BMI)
Time frame: Baseline and 6 months
Body composition and muscle strength - Timed up and go
Safety outcome for exogenous Cushing's Syndrome (Timed up and go)
Time frame: Baseline and 6 months
Body composition and muscle strength - Handgrip strength
Safety outcome for exogenous Cushing's Syndrome (Handgrip strength)
Time frame: Baseline and 6 months
Body composition and muscle strength - Short Physical Performance Battery
Safety outcome for exogenous Cushing's Syndrome (Short Physical Performance Battery)
Time frame: Baseline and 6 months
Body composition and muscle strength - Chair rising test
Safety outcome for exogenous Cushing's Syndrome (Chair rising test)
Time frame: Baseline and 6 months
Bone quality - Dual-energy X-ray absorptiometry (DXA) scan
Safety outcome for exogenous Cushing's Syndrome (DXA scan, vertebral and hip)
Time frame: Baseline and 6 months
Bone quality - bone markers in blood and urine
Safety outcome for exogenous Cushing's Syndrome (bone markers in blood and urine)
Time frame: Baseline and 6 months
Metabolic and cardiovascular risk - Automated office blood pressure
Safety outcome for exogenous Cushing's Syndrome (Automated office blood pressure)
Time frame: Baseline and 6 months
Metabolic and cardiovascular risk (Coagulation and Inflammation markers in blood)
Safety outcome for exogenous Cushing's Syndrome (Coagulation and Inflammation markers in blood)
Time frame: Baseline and 6 months
Metabolic and cardiovascular risk - Metabolic and cardiovascular markers in blood and urine
Safety outcome for exogenous Cushing's Syndrome (Metabolic and cardiovascular markers in blood and urine)
Time frame: Baseline and 6 months
Patient reported symptoms of hypercortisolism - CushingQol
Safety outcome for exogenous Cushing's Syndrome (CushingQol)
Time frame: Baseline and 6 months
Patient reported symptoms of hypercortisolism - Single item Sleep Quality Scale (SQS))
Safety outcome for exogenous Cushing's Syndrome (Single item Sleep Quality Scale (SQS))
Time frame: Baseline and 6 months
Biological integrated cortisol status assessment - ACTH test
ACTH test for normalization of adrenal function
Time frame: At baseline, (3 months) and 6 months
Biological integrated cortisol status assessment - 24h urine
24h urine for cortisol and metabolites.
Time frame: At baseline, (3 months) and 6 months
Biological integrated cortisol status assessment - Salivary cortisol/cortisone
Salivary cortisol/cortisone
Time frame: At baseline, (3 months) and 6 months
Biological integrated cortisol status assessment - Circulating biomarkers of glucocorticoid effects and adverse effects
Circulating biomarkers of glucocorticoid effects and adverse effects.
Time frame: At baseline, (3 months) and 6 months
Biological integrated cortisol status assessment - P-cortisol after 24 hours prednisolone pause.
P-cortisol after 24 hours prednisolone pause.
Time frame: At baseline, (3 months) and 6 months
ecological momentary assessments (EMA) of the Multidimensional Fatigue Inventory (MFI-20) General Fatigue scale, adjusted for EMA
EMA in situations without stress, key-secondary putcome: EMA reporting will be conducted electronically on a smartphone
Time frame: EMA is used at fixed time points monthly. Participants are asked to answer the EMA items 5 times daily at semi-randomised time points, for 3 days. Diurnal profiles are generated and one diurnal profile summarizes responses during the day across all days.
Influence of the length of the prednisolone pause (0 vs. 1 vs. 2 days) on ACTH test outcome
Forty patients (all on 5 mg prednisolone/day) will undergo two extra ACTH tests after 0 and 2 days of prednisolone pause, meaning last prednisolone dose taken on the day of the test or 2 days before the test, respectively. The exact number of hours of prednisolone pause is registered for each visit. For these patients, samples for ACTH measurements are drawn at each ACTH test, before ACTH injection.
Time frame: The ACTH tests are performed at screening (1 day pause) and two extra ACTH tests in the following weeks, every second patient starting with the 2 days pause and every second with the 0 day pause.
Prednisolone cross reactivity in the Roche Elecsys cortisol II immunoassay
Prednisolone cross reactivity in the Roche Elecsys cortisol II immunoassay at different timepoints (hours) since last prednisolone dose is determined in fourty consecutive patients by measuring plasma prednisolone concentrations with LC-MS and cortisol concentrations with both LC-MS and Roche Elecsys cortisol II immunoassay. Blood samples will be collected at 2 and 4 hours plus 1 and 2 days after the last prednisolone dose.
Time frame: Blood samples are drawn at the screening, baseline and at the two extra ACTH test visits (0 and 2 days prednisolone pause)
Plan to share: Yes — Deidentified patient data will be made available after completion of the study and publication of the main results, upon reasonable request. Data sharing will comply with GDPR and national data protection regulations.
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Studies of the drug tested here: Hydrocortisone