Hydrocortisone Versus Methylprednisolone for the Treatment of Glucocorticoid-Induced Adrenal Insufficiency

NCT07703098 | Not Yet Recruiting Phase 4

• 1 other identifier: 0120-87/2026-2711-4
• Study Type: interventional
• Target: 66
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Adrenal Insufficiency

Keywords

hydrocortisone; Glucocorticoid-Induced Adrenal Insufficiency; methylprednisolone

Outcome Measures

Primary Outcomes (1)

• 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.

  12 months

Secondary Outcomes (14)

• Secondary Analysis: Superiority of Methylprednisolone

  12 months

• Non-inferiority of Methylprednisolone at 24 Months

  24 months

• Number of adrenal crises.

  24 months

• Time required for HPA axis recovery based on the duration of previous glucocorticoid treatment.

  up to 24 months

• Predictive Value of Morning Serum Cortisol Concentration

  Baseline, 3, 6, 12, 18, 24 months.

Study Arms (2)

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.

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).

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).

Interventions

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 with hydrocortisone

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 with metylprednisolone

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• University of Ljubljana: collaborator
• University Medical Centre Ljubljana: lead

Study Sites (1)

UMC Ljubljana

Ljubljana, 1000, Slovenia

Location

MeSH Terms

Conditions

Adrenal Insufficiency

Condition Hierarchy (Ancestors)

Adrenal Gland Diseases; Endocrine System Diseases

Central Study Contacts

Živa Dolenšek, MD

CONTACT

+38615223114; ziva.dolensek@kclj.si

Tomaž Kocjan, MD PHD

CONTACT

0038615223114; tomaz.kocjan@kclj.si

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD

Study Record Dates

• First Submitted: July 2, 2026
• First Posted: July 14, 2026
• Study Start (Estimated): September 1, 2026
• Primary Completion (Estimated): September 1, 2029
• Study Completion (Estimated): September 1, 2030
• Last Updated: July 14, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will not share

Locations

SL (1)