NCT06260462

Effects of Steroid Replacement Therapy on Metabolic, Cardiovascular and Bone Outcomes in Adrenal Insufficiency

Conventional Glucocorticoids vs. Dual-release Hydrocortisone Effects on Metabolic, Cardiovascular, and Bone Outcomes in Treatment-naïve Patients With Adrenal Insufficiency: a 10-year Prospective Randomised Study

• Status: Completed
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 88 (actual)
• Sponsor: University of Palermo · Academic / Other
• Sex: All
• Age: 18 Years – 75 Years
• Healthy volunteers: Not accepted

Summary

The current study is a randomized, open study aimed to compare the effects of conventional glucocorticoid replacement treatment and dual-release hydrocortisone on anthropometric, metabolic, cardiovascular and bone outcomes in treatment-naïve patients with primary adrenal insufficiency and secondary adrenal insufficiency in a 10 year-observation period.

Detailed description

Adrenal insufficiency (AI) can be caused by a disease involving the adrenal gland resulting in inadequate secretion of adrenal cortex hormones, primary adrenal insufficiency (PAI). Secondary adrenal insufficiency (SAI) results from a decreased level of adrenocorticotrophin hormone (ACTH) released from the pituitary gland. The mainstay of treatment of PAI and SAI is glucocorticoid (GC) replacement therapy. Conventional steroid replacement therapy includes cortisone acetate and hydrocortisone administered 2-3 times a day with the highest dose in the morning and the lowest dose in the afternoon. These dosing regimens have been designed to mimic the peak of cortisol secretion in the morning and avoid overdosing during the night hours, even though a higher risk of developing comorbidities has been shown, notably in patients treated with higher evening doses. In patients with AI on conventional steroid replacement therapy, mortality remains higher than in the general population, mainly due to non-physiological daily GC overexposure and to inadequate cortisol exposure during stress-related events and illness. Studies aiming to evaluate the long-term clinical outcomes of patients with AI on conventional steroid replacement therapy clearly showed increased comorbidities, mainly related to the dose used. By contrast, dual-release hydrocortisone (DR-HC) is characterized by once-daily administration with high release of hydrocortisone immediately after intake and a very low release in the evening and nocturnal hours. The switch from conventional GC therapy to DR-HC has been shown to be associated with improvement in BMI, hepatic, bone and glucometabolic parameters and QoL. However, long-term clinical outcomes of patients treated with DR-HC in patients naïve to steroid treatment are not known.

Conditions

• Adrenal Insufficiency

Interventions

Type	Name	Description
DRUG	dual-release hydrocortisone	Oral tablets 20-25-30-40 mg/day
DRUG	Conventional glucocortidois	Oral tablets 10-15-20-25-37,5-50-62,5 mg/day

Timeline

• Start date: 2012-01-01
• Primary completion: 2022-09-30
• Completion: 2023-12-30
• First posted: 2024-02-15
• Last updated: 2024-02-15