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

Обзор

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.

Подробное описание

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.

Вмешательства

• Препарат 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).
• Препарат 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.

Первичные конечные точки

• Proportion of patients with recovery of the HPA axis. [Срок оценки: 12 months]

Вторичные конечные точки (12)

• Secondary Analysis: Superiority of Methylprednisolone [Срок оценки: 12 months]
• Non-inferiority of Methylprednisolone at 24 Months [Срок оценки: 24 months]
• Number of adrenal crises. [Срок оценки: 24 months]
• Time required for HPA axis recovery based on the duration of previous glucocorticoid treatment. [Срок оценки: up to 24 months]
• Predictive Value of Morning Serum Cortisol Concentration [Срок оценки: Baseline, 3, 6, 12, 18, 24 months.]
• Predictive Value of Serum Dehydroepiandrosterone Sulfate (DHEA-S) [Срок оценки: Baseline, 3 months, 6 months, 12 months, 18 months and 24 months]
• Predictive Value of Morning Salivary Cortisone [Срок оценки: Baseline, 3 months, 6 months, 12 months, 18 months and 24 months]
• Change from Baseline in Glycated Hemoglobin (HbA1c) [Срок оценки: Baseline, 3, 6, 12, 18, 24 months]
• Change from Baseline in Fasting Glucose [Срок оценки: Baseline, 3, 6, 12, 18 and 24 months]
• Change from Baseline in Lipid Profile [Срок оценки: Baseline, 3 months, 6 months, 12 months, 18 months, 24 months]
• Change from Baseline in Body Fat Percentage and Visceral Fat Mass [Срок оценки: Baseline, 12 months and 24 months]
• Change from Baseline in Bone Mineral Density (BMD) [Срок оценки: baseline, 12 and 24 months]

Критерии участия

Критерии включения

• 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.

Критерии исключения

• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Словения · 1 центр

• UMC Ljubljana — Ljubljana

Идентификаторы

NCT: NCT07703098 · 0120-87/2026-2711-4

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗