Adrenal InsufficiencyPhase 3NCT06260462
Effects of Steroid Replacement Therapy on Metabolic, Cardiovascular and Bone Outcomes in Adrenal Insufficiency
A Phase 3 study testing dual-release hydrocortisone and Conventional glucocortidois in people with Adrenal Insufficiency, run by University of Palermo.
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… Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Adrenal Insufficiency
- What is being tested?
- dual-release hydrocortisone and Conventional glucocortidois
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 88 participants
- Where
- No sites listed yet
- Study dates
- 1 Jan 2012to 30 Dec 2023
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Adrenal insufficiency
Who cannot join
- Exclusion criteria were adrenocortical carcinoma and congenital adrenal hyperplasia
About this study
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
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.
Read the 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
- Being tested
- dual-release hydrocortisone, Conventional glucocortidois
- Medical subject headings
- Adrenal Insufficiency
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
dual-release hydrocortisoneDrug
Also called Plenadren
Oral tablets 20-25-30-40 mg/day
Conventional glucocortidoisDrug
Also called hydrocortisone, cortisone acetate
Oral tablets 10-15-20-25-37,5-50-62,5 mg/day
| Study group | Role | What they receive |
|---|---|---|
| Conventional steroid treatment | Experimental | Cortisone acetate and hydorocortisone will be administered in two daily doses Receives: Drug: Conventional glucocortidois |
| Dual-release hydrocortisone | Experimental | Dual-release hydrocortisone will be administered once daily Receives: Drug: dual-release hydrocortisone |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change of body weight
Single outcome measurement of body weight (kg).
Measured: 0, 5 years, 10 years
Secondary outcomes (7)
Change of anthropometric parameters
waist circumference
Measured: 0, 5 years and 10 years
Change of metabolic parameters
Composite outcome including evaluation of total cholesterol, HDL cholesterol, LDL cholesterol and triglycerides, HbA1c and fasting blood glucose
Measured: 0, 5 years and 10 years
Change of insulin sensitivity parameters
the Isi-Matsuda index
Measured: 0, 5 years and 10 years
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
Measured: 0, 5 years and 10 years
Change of bone metabolic parameters
Composite outcome including calcium, phosphorus, Vitamin D, PTH, creatinine (all measured in mg/dL)
Measured: 0, 5 years and 10 years
Change of bone density
Bone mineral density quantified by Dual X-Ray Absorptiometry (DEXA)
Measured: 0, 5 years and 10 years
Change of vascular parameters
Measurement carotid intima media thickness by high-resolution M-B-mode echography
Measured: 0, 5 years and 10 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Feb 2024
- Study start1 Jan 2012
- Primary completion30 Sep 2022
- Study completion30 Dec 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Adrenal InsufficiencyStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 88 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Palermo
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Carla Giordano, University of Palermo
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06260462
- Sponsor's protocol ID
- 10 years adrenal insufficiency
- Status last verified
- Feb 2024
- First submitted
- 24 Jan 2024
- Last updated
- 15 Feb 2024
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Study protocol could be available on request
Publications
Guarnotta V, Di Stefano C, Tomasello L, Maniscalco L, Pizzolanti G, Arnaldi G, Giordano C. Conventional steroids vs. dual-release hydrocortisone on metabolic, cardiovascular, and bone outcomes in adrenal insufficiency: a 10-year study. Eur J Endocrinol. 2024 Aug 30;191(3):300-311. doi: 10.1093/ejendo/lvae107.
PubMed 39171906
Study at a glance
From the registry record, last updated by the sponsor on 15 Feb 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT06260462
- Acronym / sponsor ID
- 10 years adrenal insufficiency
- Conditions
- Adrenal Insufficiency
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 88 participants (actual)
- Lead sponsor
- University of PalermoUniversity, hospital or other
- Study start
- 1 Jan 2012 (actual)
- Primary completion
- 30 Sep 2022 (actual)
- Study completion
- 30 Dec 2023 (actual)
- First posted
- 15 Feb 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Conventional steroid treatment | Experimental | Drug: Conventional glucocortidoisCortisone acetate and hydorocortisone will be administered in two daily doses |
| Dual-release hydrocortisone | Experimental | Drug: dual-release hydrocortisoneDual-release hydrocortisone will be administered once daily |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- Adrenal insufficiency
Key exclusion criteria (1 listed)
- Exclusion criteria were adrenocortical carcinoma and congenital adrenal hyperplasia
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| dual-release hydrocortisoneAlso: PlenadrenOral tablets 20-25-30-40 mg/day | Drug | Dual-release hydrocortisone |
| Conventional glucocortidoisAlso: hydrocortisone, cortisone acetateOral tablets 10-15-20-25-37,5-50-62,5 mg/day | Drug | Conventional steroid treatment |
Primary outcome
Change of body weight
Time frame: 0, 5 years, 10 years
Single outcome measurement of body weight (kg).
7 secondary outcomes
Change of anthropometric parameters
Time frame: 0, 5 years and 10 years
Change of metabolic parameters
Time frame: 0, 5 years and 10 years
Change of insulin sensitivity parameters
Time frame: 0, 5 years and 10 years
Change of cardiovascular parameters
Time frame: 0, 5 years and 10 years
Change of bone metabolic parameters
Time frame: 0, 5 years and 10 years
Change of bone density
Time frame: 0, 5 years and 10 years
Change of vascular parameters
Time frame: 0, 5 years and 10 years
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Feb 2024.
- Derived from this study: PubMed 39171906Guarnotta V, Di Stefano C, Tomasello L, Maniscalco L, Pizzolanti G, Arnaldi G, Giordano C. Conventional steroids vs. dual-release hydrocortisone on metabolic, cardiovascular, and bone outcomes in adrenal insufficiency: a 10-year study. Eur J Endocrinol. 2024 Aug 30;191(3):300-311. doi: 10.1093/ejendo/lvae107.
- Individual participant dataSharing planned: Yes. Study protocol could be available on request
Related trials for Adrenal Insufficiency
RecruitingObservational study
Longitudinal Study of Ultra-rare Inherited Metabolic and Degenerative Neurological Diseases.
Inherited Disease, Rare Diseases
RecruitingObservational study
Natural History Study of Patients With Excess Androgen
Congenital Adrenal Hyperplasia (CAH), Familial Male-Limited Precocious Puberty (FMPP)
RecruitingObservational study
Adrenal Diseases in the Population of Modena: A Clinical-Epidemiological Database of Patients Referred to the Adrenal Disorders Outpatient Clinic of the Clinical Unit of Endocrinology at the Modena University Hospital (AOU Modena)
Cushing s Syndrome, Cushing Disease
RecruitingObservational study
Kidney Stiffness Measured by Ultrasound in Patients With High Blood Pressure and Healthy Volunteers
Arterial Hypertension, Chronic Kidney Disease, Primary Aldosteronism
Not yet recruiting
IT and IV Lentiviral Gene Therapy for X-ALD
X-linked Adrenoleukodystrophy
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing dual-release hydrocortisone and Conventional glucocortidois in people with Adrenal Insufficiency, run by University of Palermo.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 15 Feb 2024. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change of body weight (time frame: 0, 5 years, 10 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06260462, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Feb 2024.