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

Phase 3

Completed

• Conditions: Adrenal Insufficiency
• Interventions: Drug: Conventional glucocortidois; Drug: dual-release hydrocortisone

• Registration Number: NCT06260462
• Lead Sponsor: University of Palermo

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.

Study Timeline

• Study Start: 2012-01-01
• Primary Completion: 2022-09-30
• Study Completion: 2023-12-30
• Study First Submitted: 2024-01-24
• Status Verified: 2024-02
• Study First Submitted QC: 2024-02-13
• Last Update Submitted: 2024-02-13
• Study First Posted: 2024-02-15
• Last Update Posted: 2024-02-15

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 88

Inclusion Criteria

• Adrenal insufficiency

Exclusion Criteria

• Exclusion criteria were adrenocortical carcinoma and congenital adrenal hyperplasia

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Conventional steroid treatment	Conventional glucocortidois	Cortisone acetate and hydorocortisone will be administered in two daily doses
Dual-release hydrocortisone	dual-release hydrocortisone	Dual-release hydrocortisone will be administered once daily

Primary Outcome Measures

Name	Time	Method
Change of body weight	0, 5 years, 10 years	Single outcome measurement of body weight (kg).

Secondary Outcome Measures

Name	Time	Method
Change of anthropometric parameters	0, 5 years and 10 years	waist circumference
Change of cardiovascular parameters	0, 5 years and 10 years	Measurement of interventricular septum at diastole (IVSd) and the thickness of the posterior wall (PWT) by high-resolution M-B-mode transthoracic echocardiography
Change of bone metabolic parameters	0, 5 years and 10 years	Composite outcome including calcium, phosphorus, Vitamin D, PTH, creatinine (all measured in mg/dL)
Change of metabolic parameters	0, 5 years and 10 years	Composite outcome including evaluation of total cholesterol, HDL cholesterol, LDL cholesterol and triglycerides, HbA1c and fasting blood glucose
Change of insulin sensitivity parameters	0, 5 years and 10 years	the Isi-Matsuda index
Change of bone density	0, 5 years and 10 years	Bone mineral density quantified by Dual X-Ray Absorptiometry (DEXA)
Change of vascular parameters	0, 5 years and 10 years	Measurement carotid intima media thickness by high-resolution M-B-mode echography