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
Overview
- Phase
- Phase 3
- Intervention
- Conventional glucocortidois
- Conditions
- Adrenal Insufficiency
- Sponsor
- University of Palermo
- Enrollment
- 88
- Primary Endpoint
- Change of body weight
- Status
- Completed
- Last Updated
- 2 years ago
Overview
Brief 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.
Investigators
Carla Giordano
professor
University of Palermo
Eligibility Criteria
Inclusion Criteria
- •Adrenal insufficiency
Exclusion Criteria
- •Exclusion criteria were adrenocortical carcinoma and congenital adrenal hyperplasia
Arms & Interventions
Conventional steroid treatment
Cortisone acetate and hydorocortisone will be administered in two daily doses
Intervention: Conventional glucocortidois
Dual-release hydrocortisone
Dual-release hydrocortisone will be administered once daily
Intervention: dual-release hydrocortisone
Outcomes
Primary Outcomes
Change of body weight
Time Frame: 0, 5 years, 10 years
Single outcome measurement of body weight (kg).
Secondary Outcomes
- Change of anthropometric parameters(0, 5 years and 10 years)
- Change of cardiovascular parameters(0, 5 years and 10 years)
- Change of bone metabolic parameters(0, 5 years and 10 years)
- Change of metabolic parameters(0, 5 years and 10 years)
- Change of insulin sensitivity parameters(0, 5 years and 10 years)
- Change of bone density(0, 5 years and 10 years)
- Change of vascular parameters(0, 5 years and 10 years)