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NCT Number: NCT06260462

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

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.

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Key information

Conditions

Adrenal Insufficiency Adrenal Gland Diseases Endocrine System Diseases

Age range

18 year–75 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Adrenal insufficiency

Exclusion criteria

  • Exclusion criteria were adrenocortical carcinoma and congenital adrenal hyperplasia

Treatment and study plan

dual-release hydrocortisone

Drug

Oral tablets 20-25-30-40 mg/day

Other names: Plenadren

Conventional glucocortidois

Drug

Oral tablets 10-15-20-25-37,5-50-62,5 mg/day

Other names: hydrocortisone, cortisone acetate

Primary outcomes

  1. Change of body weight

    Time frame: 0, 5 years, 10 years

    Single outcome measurement of body weight (kg).

Secondary outcomes

  1. Change of anthropometric parameters

    Time frame: 0, 5 years and 10 years

    waist circumference

  2. Change of metabolic parameters

    Time frame: 0, 5 years and 10 years

    Composite outcome including evaluation of total cholesterol, HDL cholesterol, LDL cholesterol and triglycerides, HbA1c and fasting blood glucose

  3. Change of insulin sensitivity parameters

    Time frame: 0, 5 years and 10 years

    the Isi-Matsuda index

  4. Change of cardiovascular parameters

    Time frame: 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

  5. Change of bone metabolic parameters

    Time frame: 0, 5 years and 10 years

    Composite outcome including calcium, phosphorus, Vitamin D, PTH, creatinine (all measured in mg/dL)

  6. Change of bone density

    Time frame: 0, 5 years and 10 years

    Bone mineral density quantified by Dual X-Ray Absorptiometry (DEXA)

  7. Change of vascular parameters

    Time frame: 0, 5 years and 10 years

    Measurement carotid intima media thickness by high-resolution M-B-mode echography

Sponsors and collaborators

Lead sponsor

University of Palermo

Other

Registry information

Official study 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

Important dates

Study start
2012
Primary completion
2022
Study completion
2023
First posted
Feb 15, 2024
Registry last updated
Feb 15, 2024

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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