A Phase 4 interventional study of Patients will receive 3 mg of methylprednisolone once daily. The dose is administered in the morning (1 ½ tablets of 2 mg Medrol after breakfast). and Patients will receive 15 mg of hydrocortisone daily. The dose is split into 10 mg in the morning after breakfast and 5 mg after 6-7 hours. in Adrenal Insufficiency, sponsored by University Medical Centre Ljubljana. Not yet recruiting at 1 site in Slovenia. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-07-14.
Sponsored by University Medical Centre Ljubljana · Phase 4, Interventional, and Treatment
This study aims to compare the use of methylprednisolone and hydrocortisone as replacement therapies in patients with glucocorticoid-induced adrenal insufficiency.
The primary goal is to evaluate and compare the recovery of the hypothalamic-pituitary-adrenal (HPA) axis.
Glucocorticoids in supraphysiological doses are the most frequent cause of adrenal insufficiency due to the suppression of the hypothalamic-pituitary-adrenal (HPA) axis.
In cases of confirmed adrenal insufficiency, current guidelines recommend replacement therapy with physiological doses of short- and intermediate-acting glucocorticoids to prevent adrenal crises without inhibiting HPA axis recovery.
While hydrocortisone is the most commonly used short-acting glucocorticoid, methylprednisolone is widely prescribed in Slovenia.
Because methylprednisolone lacks mineralocorticoid effects, it appears to be a particularly suitable choice for patients with glucocorticoid-induced adrenal insufficiency, where mineralocorticoid secretion is not impaired.
This randomized, prospective, open-label interventional study will primarily evaluate non-inferiority regarding HPA axis recovery after 12 months, with a long-term assessment at 24 months.
Patients will undergo testing at baseline, 3, 6,12, 18, 24 months (or until HPA axis recovery), including laboratory tests, short ACTH tests, body composition measurements, and quality of life questionnaires.
136 studies on the registry are indexed under Adrenal Insufficiency; 27 are open to participants now.
This study's planned enrollment of 66 is above the median of 44 across 71 interventional studies indexed under Adrenal Insufficiency.
Browse Adrenal Insufficiency studies →University Medical Centre Ljubljana is the lead sponsor of 296 studies on the registry; 72 are open to participants now.
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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.
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.
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.
The study doctor’s estimate of how long someone is likely to live. Criteria use it so that people can stay in the study long enough for it to answer its question.
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.
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.
Life expectancy
The study doctor’s estimate of how long someone is likely to live. Criteria use it so that people can stay in the study long enough for it to answer its question.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Patients will receive 15 mg of hydrocortisone daily. The dose is split into 10 mg in the morning after breakfast and 5 mg after 6-7 hours.
Drug: Patients will receive 15 mg of hydrocortisone daily. The dose is split into 10 mg in the morning after breakfast and 5 mg after 6-7 hours.
Patients will receive 3 mg of methylprednisolone once daily. The dose is administered in the morning (1 ½ tablets of 2 mg methylprednisolone after breakfast).
Drug: Patients will receive 3 mg of methylprednisolone once daily. The dose is administered in the morning (1 ½ tablets of 2 mg Medrol after breakfast).
Patients will receive 3 mg of methylprednisolone once daily. The dose is administered in the morning (1 ½ tablets of 2 mg methylprednisolone after breakfast).
Patients will receive 15 mg of hydrocortisone daily. The dose is split into 10 mg in the morning after breakfast and 5 mg after 6-7 hours.
Proportion of patients with recovery of the HPA axis.
Replacement therapy for glucocorticoid-induced adrenal insufficiency with methylprednisolone in a physiologically equivalent morning dose is being evaluated for non-inferiority compared to hydrocortisone. Methylprednisolone is considered not inferior regarding the proportion of patients with HPA axis recovery after 12 months, provided the difference between the groups does not exceed the pre-specified non-inferiority margin of 10%. Recovery of the HPA axis is assessed via a short ACTH test, defined as a cortisol rise to at least 470 nmol/L after 30 minutes or at least 500 nmol/L after 60 minutes.
Time frame: 12 months
Secondary Analysis: Superiority of Methylprednisolone
If the non-inferiority of methylprednisolone is confirmed, we will also evaluate the superiority of methylprednisolone as part of the secondary analyses: The proportion of patients with recovery of the HPA axis will be higher after 12 months in the group receiving methylprednisolone.
Time frame: 12 months
Non-inferiority of Methylprednisolone at 24 Months
Methylprednisolone is not inferior to hydrocortisone in the treatment of glucocorticoid-induced adrenal insufficiency after 24 months. The difference in the proportion of patients with HPA axis recovery between the groups does not exceed the pre-specified non-inferiority margin (15%).
Time frame: 24 months
Number of adrenal crises.
Time frame: 24 months
Time required for HPA axis recovery based on the duration of previous glucocorticoid treatment.
Time frame: up to 24 months
Predictive Value of Morning Serum Cortisol Concentration
Morning serum cortisol levels (in nmol/L) measured to evaluate their predictive value for the short ACTH test outcome.
Time frame: Baseline, 3, 6, 12, 18, 24 months.
Predictive Value of Serum Dehydroepiandrosterone Sulfate (DHEA-S)
Morning serum DHEA-S levels measured to evaluate their predictive value for the short ACTH test outcome.
Time frame: Baseline, 3 months, 6 months, 12 months, 18 months and 24 months
Predictive Value of Morning Salivary Cortisone
Cortisone levels in morning saliva evaluated as a potential non-invasive predictor for the short ACTH test outcome
Time frame: Baseline, 3 months, 6 months, 12 months, 18 months and 24 months
Change from Baseline in Glycated Hemoglobin (HbA1c)
Long-term glycemic control assessed by measuring HbA1c levels, expressed as a percentage (%)
Time frame: Baseline, 3, 6, 12, 18, 24 months
Change from Baseline in Fasting Glucose
Plasma glucose concentrations are measured in mmol/L.
Time frame: Baseline, 3, 6, 12, 18 and 24 months
Change from Baseline in Lipid Profile
Metabolic assessment including total cholesterol, high-density lipoprotein (HDL), low-density lipoprotein (LDL), and triglycerides, measured in mmol/L via a standard fasting blood test.
Time frame: Baseline, 3 months, 6 months, 12 months, 18 months, 24 months
Change from Baseline in Body Fat Percentage and Visceral Fat Mass
Body composition (total body fat percentage and visceral fat mass) measured using Dual-Energy X-ray Absorptiometry (DXA).
Time frame: Baseline, 12 months and 24 months
Change from Baseline in Bone Mineral Density (BMD)
Bone mineral density measured using Dual-Energy X-ray Absorptiometry (DXA).
Time frame: baseline, 12 and 24 months
Change from Baseline in Quality of Life Assessed by the 36-Item Short Form Health Survey (SF-36)
the SF-36 is a self-administered questionnaire measuring health-related quality of life across eight domains. Scores range from 0 to 100, where higher scores indicate a better health state and lower disability.
Time frame: Time Frame: Baseline, 6, 12, 24 months.
Change from Baseline in Treatment Satisfaction Assessed by the Treatment Satisfaction Questionnaire for Medication (TSQM - 1.4)
The TSQM is a validated questionnaire assessing patient satisfaction with medication across domains such as effectiveness, side effects, and convenience. Scores for each domain range from 0 to 100, where higher scores indicate greater satisfaction with the treatment.
Time frame: 3, 12 and 24 months
Plan to share: No
No publications or documents are linked to this record.
Start is estimated for Sep 2026; primary completion for Sep 2029, 36 months later.
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