Adrenal InsufficiencyPhase 4NCT07703098
Hydrocortisone Versus Methylprednisolone for the Treatment of Glucocorticoid-Induced Adrenal Insufficiency
A Phase 4 study testing 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 people with Adrenal Insufficiency, run by University Medical Centre Ljubljana at 1 site in Slovenia.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Adrenal Insufficiency
- What is being tested?
- 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.
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 66 participants
- Where
- 1 siteSlovenia
- Study dates
- 1 Sep 2026to 1 Sep 2030
- Phase
- Phase 4
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age over 18 years.
- Suspected adrenal insufficiency due to receiving supraphysiological doses of methylprednisolone for more than 4 weeks.
- Receiving methylprednisolone 4 mg for at least the last 4 weeks.
- Morning cortisol lower than 300 nmol/L.
- Inadequate result of a short ACTH test performed on a physiological dose of methylprednisolone (cortisol rise after 30 min under 470 nmol/L AND after 60 min under 500 nmol/L).
- No further indication for treating the underlying disease, and retreatment with glucocorticoids is not expected in the next 2 years.
- Consent to participate in the research.
Who cannot join
- Known organic disease of the pituitary-adrenal axis.
- Body mass over 130 kg.
- Advanced comorbidities.
- Advanced heart failure (NYHA IV).
- Chronic kidney disease IV, eGFR under 30 ml/min.
- Liver cirrhosis.
Show all 14Show fewer
- Active malignant disease.
- Immune deficiencies.
- Planned major surgery during the study duration.
- Receiving drugs affecting cortisol metabolism or interfering with cortisol measurements (e.g., systemic estrogens, strong inducers or inhibitors of CYP3A4).
- Conditions affecting cortisol metabolism (pregnancy, liver disease, nephrotic syndrome).
- Alcohol dependence syndrome (consuming more than 21 units of alcohol per week).
- Shift (night) work.
- Presence of comorbidities with an expected life expectancy of less than 3 years.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Slovenia1 site
UMC Ljubljana
Ljubljana, 1000
živa dolenšek, MD, 003865223114, ziva.dolensek@kclj.si
Tomaž Kocjan, MD PHD, 0038615223114, tomaz.kocjan@kclj.si
About this study
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.
Read the detailed description
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.
- Conditions
- Adrenal Insufficiency
- Being tested
- 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 15 mg of hydrocortisone daily. The dose is split into 10 mg in the morning after breakfast and 5 mg after 6-7 hours.
- Keywords
- hydrocortisone, Glucocorticoid-Induced Adrenal Insufficiency, methylprednisolone
- Medical subject headings
- Adrenal Insufficiency
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
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).Drug
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.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.
| Study group | Role | What they receive |
|---|---|---|
| patients with hydrocortisone | Active comparator | 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. Receives: 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 with metylprednisolone | Experimental | 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). Receives: 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). |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 12 months
Secondary outcomes (14)
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.
Measured: 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%).
Measured: 24 months
Number of adrenal crises.
Measured: 24 months
Time required for HPA axis recovery based on the duration of previous glucocorticoid treatment.
Measured: 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.
Measured: 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.
Measured: 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
Measured: 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 (%)
Measured: Baseline, 3, 6, 12, 18, 24 months
Change from Baseline in Fasting Glucose
Plasma glucose concentrations are measured in mmol/L.
Measured: 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.
Measured: 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).
Measured: 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).
Measured: 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.
Measured: 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.
Measured: 3, 12 and 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Jul 2026
- Study start1 Sep 2026 (estimated)
- Primary completion1 Sep 2029 (estimated)
- Study completion1 Sep 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Adrenal InsufficiencyStudies of the same condition, open and under way.
- More trials run by University Medical Centre LjubljanaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 66 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University Medical Centre Ljubljana
- Sponsor type
- University, hospital or other
- Collaborators
- University of Ljubljana
- Responsible party
- Principal investigator, Živa Dolenšek, University Medical Centre Ljubljana
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07703098
- Sponsor's protocol ID
- 0120-87/2026-2711-4
- Status last verified
- Jul 2026
- First submitted
- 2 Jul 2026
- Last updated
- 14 Jul 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 14 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Hydrocortisone Versus Methylprednisolone for the Treatment of Glucocorticoid-Induced Adrenal Insufficiency
- ClinicalTrials.gov ID
- NCT07703098
- Acronym / sponsor ID
- 0120-87/2026-2711-4
- Conditions
- Adrenal Insufficiency
- Keywords
- hydrocortisone, Glucocorticoid-Induced Adrenal Insufficiency, methylprednisolone
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 66 participants (estimated)
- Lead sponsor
- University Medical Centre LjubljanaUniversity, hospital or other
- Collaborators
- University of Ljubljana
- Study start
- 1 Sep 2026 (estimated)
- Primary completion
- 1 Sep 2029 (estimated)
- Study completion
- 1 Sep 2030 (estimated)
- First posted
- 14 Jul 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| patients with hydrocortisone | Active comparator | 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 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 with metylprednisolone | Experimental | 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). |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Age over 18 years.
- Suspected adrenal insufficiency due to receiving supraphysiological doses of methylprednisolone for more than 4 weeks.
- Receiving methylprednisolone 4 mg for at least the last 4 weeks.
- Morning cortisol lower than 300 nmol/L.
- Inadequate result of a short ACTH test performed on a physiological dose of methylprednisolone (cortisol rise after 30 min under 470 nmol/L AND after 60 min under 500 nmol/L).
Key exclusion criteria (14 listed)
- Known organic disease of the pituitary-adrenal axis.
- Body mass over 130 kg.
- Advanced comorbidities.
- Advanced heart failure (NYHA IV).
- Chronic kidney disease IV, eGFR under 30 ml/min.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 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). | Drug | patients with metylprednisolone |
| 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 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 with hydrocortisone |
Primary outcome
Proportion of patients with recovery of the HPA axis.
Time frame: 12 months
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.
14 secondary outcomes
Secondary Analysis: Superiority of Methylprednisolone
Time frame: 12 months
Non-inferiority of Methylprednisolone at 24 Months
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
Time frame: Baseline, 3, 6, 12, 18, 24 months.
Predictive Value of Serum Dehydroepiandrosterone Sulfate (DHEA-S)
Time frame: Baseline, 3 months, 6 months, 12 months, 18 months and 24 months
Predictive Value of Morning Salivary Cortisone
Time frame: Baseline, 3 months, 6 months, 12 months, 18 months and 24 months
Change from Baseline in Glycated Hemoglobin (HbA1c)
Time frame: Baseline, 3, 6, 12, 18, 24 months
Change from Baseline in Fasting Glucose
Time frame: Baseline, 3, 6, 12, 18 and 24 months
Change from Baseline in Lipid Profile
Time frame: Baseline, 3 months, 6 months, 12 months, 18 months, 24 months
Change from Baseline in Body Fat Percentage and Visceral Fat Mass
Time frame: Baseline, 12 months and 24 months
Change from Baseline in Bone Mineral Density (BMD)
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)
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)
Time frame: 3, 12 and 24 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Jul 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing 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 people with Adrenal Insufficiency, run by University Medical Centre Ljubljana at 1 site in Slovenia.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 14 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Slovenia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Živa Dolenšek, MD (+38615223114, ziva.dolensek@kclj.si), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Proportion of patients with recovery of the HPA axis. (time frame: 12 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Jul 2026.