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

Adrenal Insufficiency Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT06260462
• Other study ID #: 10 years adrenal insufficiency
• Status: Completed
• Phase: Phase 3
• Start date: January 1, 2012
• Est. completion date: December 30, 2023

Study information

• Verified date: February 2024
• Source: University of Palermo
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 88
• Est. completion date: December 30, 2023
• Est. primary completion date: September 30, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

• Adrenal insufficiency

Exclusion Criteria:

• Exclusion criteria were adrenocortical carcinoma and congenital adrenal hyperplasia

Related Conditions & MeSH terms

• Adrenal Insufficiency

Intervention

Drug:
• dual-release hydrocortisone
Oral tablets 20-25-30-40 mg/day
• Conventional glucocortidois
Oral tablets 10-15-20-25-37,5-50-62,5 mg/day

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
University of Palermo

Outcome

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