A Phase 4 interventional study of Hydrocortisone and Placebo in Adrenal Insufficiency, Polymyalgia Rheumatica (PMR) and Giant Cell Arteritis (GCA), sponsored by Marianne Andersen. Recruiting at 3 sites in Denmark. Open to participants aged 50 Years and older. Per ClinicalTrials.gov, last updated 2025-12-22.
Sponsored by Marianne Andersen · Phase 4, Interventional, and Treatment
Cortisol, a glucocorticoid (GC) hormone secreted from the adrenal glands, is essential for survival. Cortisol also possesses anti-inflammatory actions and GC formulations (prednisolone) are used to treat many inflammatory diseases and conditions. Indeed, three percent of the Danish population (≈ 180.000 individuals) redeems at least one prescription of synthetic GC per year and at least 20,000 patients annually discontinue GC treatment. Pharmacological GC therapy suppresses endogenous cortisol production and thereby induce relative adrenal insufficiency (GIA). The risk of GIA as determined by the adrenal corticotrophic hormone (ACTH) stimulation test has previously been reported to ≈ 25 %, but testing after GC treatment is not routinely performed. Indeed, new evidence suggest that the risk of GIA after planned cessation of prednisolone treatment for polymyalgia rheumatic (PMR) or giant cell arteritis (GCA) is substantially lower, probably 2%. The reason for this discrepancy is undoubtedly selection bias in the previous publications and the use of inaccurate cortisol assays. At the same time, however, it was observed that 25% exhibited pronounced symptoms of adrenal insufficiency based on a questionnaire specific for detecting symptoms of adrenal insufficiency, the so-called AddiQoL-30. Concomitantly, the basal cortisol levels in the same group were significantly lower as compared to the group, who exhibited milder or no symptoms attributable to adrenal insufficiency. This observation aligns with the clinical experience that PMR/GCA patients often complain of fatigue after planned cessation of prednisolone treatment. This often occurs in the absence of objective symptoms or signs of residual PMR/GCA disease activity. The scenario has been designated as "the steroid withdrawal syndrome". This may represent a state of relative adrenal insufficiency prompted by long term, high dose prednisolone treatment. The proper way to tackle this clinical conundrum is to perform a proper randomized trial, which so far has not been conducted.
Therefore, investigators of this study will perform the first placebo-controlled randomised controlled trial (RCT) in patients with PMR and GCA after planned cessation of GC treatment. Investigators argue that neither watchful waiting nor routine hydrocortisone replacement are infallible. The study will be the first evidence-based guidance and aid to GIA patients and thus meet an important need for many thousand patients.
136 studies on the registry are indexed under Adrenal Insufficiency; 27 are open to participants now.
This study's planned enrollment of 100 is above the median of 44 across 71 interventional studies indexed under Adrenal Insufficiency.
Browse Adrenal Insufficiency studies →Marianne Andersen is the lead sponsor of 5 studies on the registry; 2 are open to participants now.
Counted across the registry records on this site, refreshed daily.
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.
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.
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.
Included patients with an AddiQoL-30 score \< 85 and/or short Synacthen test stimulated plasma cortisol levels \> 100 and \< 420 nmol/L that are radomized to recieve placebo tablets.
Drug: Placebo
Included patients with an AddiQoL-30 score \< 85 and/or short Synacthen test stimulated plasma cortisol levels \> 100 and \< 420 nmol/L that are radomized to recieve hydrocortisone tablets.
Drug: Hydrocortisone
Patients with an AddiQoL-30 score \> 85 and short Synacthen test stimulated plasma cortisol level \> 420 nmol/L. Patients undergo baseline examination only.
Patients with pronounced adrenal insufficiency (short Synacthen test stimulated plasma cortisol levels \< 100 nmol/L) - regardless of AddiQoL-30 score. These patients undergo baseline examination and commence open hydrocortisone replacement according to standard clinical practice.
Patients are randomized to oral hydrocortisone (10 mg twice daily) or placebo for 16 weeks.
Patients are randomized to oral hydrocortisone (10 mg twice daily) or placebo for 16 weeks.
Adrenal insufficiency symptoms
Symptoms measured by the Addison's disease-specific quality of life questionnaire (AddiQoL-30), which consists of 30 questions focusing on common symptoms of adrenal insufficiency related to quality of life. Each item belongs to one of following subthemes: fatigue, symptoms, emotions and miscellaneous. Each question can be scored from 1 (none of the time/strongly disagree) to 6 (all of the time/strongly agree) and yields a score between 1 - 4 arbitrary units. This adds up to a total score ranging from 30 (worst quality of life) to 120 (best quality of life).
Time frame: Screening and 16 weeks
Patient-reported symptoms via mobile phone app - PRO-CTCAETM
Symptoms of fatigue, nausea, dizziness, and "feeling generally unwell" assessed by the Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAETM). Each symptom is evaluated in terms of frequency and severity with a score from 1 (never/nothing) to 5 (almost constant/very strong).
Time frame: Patients are asked daily throughout the study period.
Patient-reported symptoms via mobile phone app - EMA-MFI
Four statements regarding diurnal fatigue based on the validated General Fatigue Scale from the Multidimensional Fatigue Inventory (MFI-20) adapted for Ecological Momentary Assessments (EMA). Each statement is answered by a visuel scale from left (yes, that is correct) to right (no, that is not correct).
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.
Cushing quality of life (CushingQoL)
Cushing quality of life (CushingQoL) is a disease-specific questionnaire for patients with endogenous cortisol excess. It consists of 12 items about mental and physical adverse effects of cortisol excess. The total score os normalised to a scale ranging from 0 (lowest quality of lige) to 100 (highest quality of life).
Time frame: Baseline and 16 weeks
The short form 36 (SF-36)
SF-36 is a genereic qeustionnaire evaluating general health perception with 36 items related to 8 dimensions: physical functioning for the limitation in performing all physical activities; role physical for problems with work or other daily activities; bodily pain; general health; vitality; social functioning; role emotional; and mental health.
Time frame: Baseline and 16 weeks
Sleep Quality Scale (SQS)
SQS is a single item questionnaire consisting of a numerical rating scale to evaluate the overall sleep quality over the last 7 nights. The scale is ranging from 0 (terrible sleep) to 10 (excellent sleep).
Time frame: Baseline and 16 weeks
International Physical Activity Questionnaire, short form, 7 days (IPAQ-7s)
The IPAQ-7s records types and intensity of physical activity. The questionnaire consists of seven open items covering 4 types of activity (energetic activity, moderate activity, walk, and sitting). The first three is measured in "number of days per week", "hours per day", and "minutes per day". The last activity (sitting) is measured in "hours per day" and "minutes per day".
Time frame: Baseline and 16 weeks
Incidence of adrenal crises
Incidence of adrenal crises, including information on hospitalizations, number of sick days, diagnoses and therapy.
Time frame: 16 weeks
Cardiovascular health - Blood pressure
Office blood pressure (OBP) and automated blood pressure (AOBP). Blood pressure measurements will be performed with (OBP) and without (AOBP) the presence of investigator. Unit is mmHg.
Time frame: Baseline and 16 weeks
Cardiovascular health - PWV
Arterial stiffness and pulse wave velocity (PWV). PVW is measured three times, unit is m/s.
Time frame: Baseline and 16 weeks
Body composition - DXA scan
Body composition by dual X-ray absorptiometry (DXA) scan. Body composition is measured in the distribution of fat and lean mass in grams (g).
Time frame: Only performed at baseline visit
Bone quality - DXA scan
Bone quality by dual X-ray absorptiometry (DXA) scan. Bone mineral density (g/cm\^2) and T-score of the lumbal spine and hip.
Time frame: Only performed at baseline visit
HR-pQCT
High-resolution peripheral quantitative computed tomography (HR-pQCT) in order to obtain three-dimensional BMD.
Time frame: Only performed at baseline visit
Muscle function and physical activity - Handgrip strength.
Handgrip strength is measured in kg using a hydraulic hand dynamometer.
Time frame: Baseline and 16 weeks.
Muscle function and physical activity - TUG
Timed Up and Go (TUG) test measures the time taken to stand up, walk three meters in a straight line, and immediately return to the chair.
Time frame: Baseline and 16 weeks.
Muscle function and physical activity - SPPB
The Short Physical Performance Battery including Chair Rising Test (SPPB) evaluates the lower extremity function of the patient.
Time frame: Baseline and 16 weeks.
Muscle function and physical activity - Actigraph
Patients are asked to wear an accelerometer device on their non-dominant wrist to measure physical activity and sleep. Time of physical activity and sleep will be measured in minutes.
Time frame: Baseline and 16 weeks, duration: 7 days
Muscle function and physical activity - Muscle power
The muscle power of the dominant arm and upper back, as well as elbow, hip, and knee extension and flexion, are evaluated by use of a exercise machine. Power is measured in watt.
Time frame: Baseline and 16 weeks.
Muscle function and physical activity - Isometric muscle strength
The isometric muscle strength of the dominant arm and upper back, as well as elbow, hip, and knee extension and flexion, are evaluated by use of a exercise machine. Strength is measured in kg.
Time frame: Baseline and 16 weeks.
Normalization of adrenal function evaluated by SST
Short Synacthen® test. Cortisol is measured in nmol/L before (0 min) and after (30 min) administration of 1 ml Synacthen (0.25 mg/ml).
Time frame: Screening/Baseline and 16 weeks
Blood samples (unit: 10E12/L)
Standardised fasting morning blood samples will be drawn after the patient has been resting in a sitting position for 15 minutes. Erythrocytes.
Time frame: Baseline and 16 weeks
Blood samples (unit: fmol)
Standardised fasting morning blood samples will be drawn after the patient has been resting in a sitting position for 15 minutes. MCH.
Time frame: Baseline and 16 weeks
Blood samples (unit: 10E9/L).
Standardised fasting morning blood samples will be drawn after the patient has been resting in a sitting position for 15 minutes. Leokocytes; neutrophils; lymphocytes; monocytes; basophilocytes; eosinophils; metamyelocytes; thrombocytes.
Time frame: Baseline and 16 weeks
Blood samples (unit: mmol/L)
Standardised fasting morning blood samples will be drawn after the patient has been resting in a sitting position for 15 minutes. Hemoglobin; MCHC; glucose; glucose derived from HbA1c, cholesterol; HDL; LDL; non-HDL; triglycerid; calcium ion, free.
Time frame: Baseline and 16 weeks
Blood samples (unit: mmol/mol)
Standardised fasting morning blood samples will be drawn after the patient has been resting in a sitting position for 15 minutes. HbA1c.
Time frame: Baseline and 16 weeks
Blood samples (unit: IU/L)
Standardised fasting morning blood samples will be drawn after the patient has been resting in a sitting position for 15 minutes. FSH; LH.
Time frame: Baseline and 16 weeks
Blood samples (unit: µg/L).
Standardised fasting morning blood samples will be drawn after the patient has been resting in a sitting position for 15 minutes. IGF-1.
Time frame: Baseline and 16 weeks
Blood samples (unit: pmol/L)
Standardised fasting morning blood samples will be drawn after the patient has been resting in a sitting position for 15 minutes. ACTH.
Time frame: Baseline and 16 weeks
Blood samples (unit: 10E-3IU/L)
Standardised fasting morning blood samples will be drawn after the patient has been resting in a sitting position for 15 minutes. Prolactin; TSH.
Time frame: Baseline and 16 weeks
Blood samples (unit: nmol/L)
Standardised fasting morning blood samples will be drawn after the patient has been resting in a sitting position for 15 minutes. SHBG; testosterone; T4; estradiol.
Time frame: Baseline and 16 weeks
Blood samples (unit: mg/L)
Standardised fasting morning blood samples will be drawn after the patient has been resting in a sitting position for 15 minutes. C-reactive protein (CRP).
Time frame: Baseline and 16 weeks
Diurnal urine samples
24 hours urine sampling are stored at -80C until analysis. Cortisol metabolites will be measured in nmol/24h.
Time frame: Baseline and 16 weeks
Hair samples
Two hair samples are collected. Each sample is a section of hair strands approximately 3 mm in diameter and cut as close as possible to the scalp with a scissor. The hair samples are collected from the posterior vertex area. The cut end of the hair strands is marked. The samples are stored in a dry and cool place for later analysis of hair cortisol levels.
Time frame: Baseline and 16 weeks
Saliva samples
Fasting saliva samples are collected to measure salivary cortisol.
Time frame: Baseline and 16 weeks
Continous glucose monitoring (CGM)
Patients will wear a Dexcom G6 sensor to measure glucose levels.
Time frame: Baseline and 16 weeks, duration: 7 days
Muscle biopsies
Patients attending Aarhus University Hospital will be requested to provide muscle and fat biopsies. During sterile conditions and local anaesthesia, muscle biopsies (≈ 500 mg) are obtained from the vastus lateralis of the quadriceps femoris muscle 10-15 cm proximal to the patella using a Bergström biopsy needle.
Time frame: Baseline and 16 weeks
Fat biopsies
Patients attending Aarhus University Hospital will be requested to provide muscle and fat biopsies. Adipose tissue biopsies (≈ 20 ml) are obtained by liposuction from the abdominal subcutaneous fat depots during local anaesthesia.
Time frame: Baseline and 16 weeks
Physical examination - Height
Height is measured in cm.
Time frame: Baseline and 16 weeks
Physical examination - Weight
Weight is measured in kg.
Time frame: Baseline and 16 weeks
Physical examination - waist and hip circumference.
Waist and hip circumference are measured in cm.
Time frame: Baseline and 16 weeks
Plan to share: No — Deidentified participant 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.
Started Feb 2022 (actual). Primary completion is estimated for Jan 2026, 47 months after the start.
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Studies of the drug tested here: Hydrocortisone
Marianne Andersen