Congenital Adrenal HyperplasiaPhase 4CareOnTIMENCT03760835
Congenital Adrenal Hyperplasia Once Daily Hydrocortisone Treatment
A Phase 4 study testing Conventional Glucocorticoids (immediate release hydrocortisone, cortisone acetate, prednisone, prednisolone, dexamethasone) and Dual release hydrocortisone (plenadren) in people with Congenital Adrenal Hyperplasia, run by Federico II University at 1 site in Italy.
Trial summary
This is a controlled, open study designed to compare the effects of dual-release hydrocortisone preparations versus conventional glucocorticoid therapy on clinical, anthropometric parameters, metabolic syndrome, hormonal profile, bone status, quality of life, reproductive, sexual and psychological functions and… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Congenital Adrenal Hyperplasia
- What is being tested?
- Conventional Glucocorticoids (immediate release hydrocortisone, cortisone acetate, prednisone, prednisolone, dexamethasone) and Dual release hydrocortisone (plenadren)
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 150 participants
- Where
- 1 siteItaly
- Study dates
- 11 Aug 2016to 31 Dec 2027
- Phase
- Phase 4
- Are there results?
- Not yet: the study is under way
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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- males and females aged >18 years;
- established diagnosis of adrenal insufficiency in congenital adrenal hyperplasia due to 21-hydroxylase deficiency;
- stably treated with conventional glucocorticoids, available to change their regimen according to random allocation
- written informed consent/assent to participate in the study in compliance with local regulations.
Who cannot join
- clinical or laboratory signs of severe cerebral, respiratory, hepatobiliary or pancreatic diseases, renal dysfunction, gastrointestinal emptying, or motility disturbances (i.e. chronic diarrhea), significant psychiatric illnesses;
- history of/or current alcohol and/or drug abuse;
- night shift workers;
- underlying diseases that could necessitate treatment with glucocorticoids;
- therapies with hepatic enzyme induction drugs interfering with glucocorticoid kinetics, or immunosuppressive steroid therapy;
- patients with a documented intolerance/known hypersensitivity to dual release hydrocortisone;
- vulnerable populations, such as elderly, cancer patients, pregnant and lactating women;
- history of non-compliance to medical regimens, or potentially unreliable patients
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Italy1 site, 1 recruiting
- Recruiting
Federico II University
Naples, 80131
Rosario Pivonello, MD,PhD,Professor, +390817464983, rosario.pivonello@unina.it
Rosario Pivonello, MD, PhD, Professor
About this study
Official title: Congenital Adrenal Hyperplasia: Innovative Once Daily Dual Release Hydrocortisone Treatment
This is a controlled, open study designed to compare the effects of dual-release hydrocortisone preparations versus conventional glucocorticoid therapy on clinical, anthropometric parameters, metabolic syndrome, hormonal profile, bone status, quality of life, reproductive, sexual and psychological functions and treatment compliance in patients affected by congenital adrenal hyperplasia due to 21 OH deficiency.
Read the detailed description
Congenital adrenal hyperplasia due to 21-hydroxylase deficiency is an autosomal recessive disorder characterized by cortisol and in some cases aldosterone deficiency, associated with androgen excess. Treatment goals are to replace cortisol deficiency, to control androgen levels, while avoiding the adverse effects of exogenous glucocorticoids. A variety of glucocorticoid treatments have been used in an attempt to control the overnight increase in adrenal androgens. However, there is no consensus on the optimum management of congenital adrenal hyperplasia adults. Current evidence in patients with adrenal insufficiency suggests that the inability of current regimens to replace physiological circadian cortisol levels, leads to adverse clinical outcomes, including metabolic syndrome, insulin resistance, increased risk factors for cardiovascular diseases, bone and immune alterations, sleep disturbances and quality of life impairment. Moreover, the risk for poor treatment compliance, in case of multiple daily doses treatment regimens, should not be excluded. In this trial a dual-release hydrocortisone preparation, that been able to mimic the circadian pattern of circulating cortisol, was studied in patients with adrenal insufficiency due to congenital adrenal hyperplasia.
All patients with a diagnosis of congenital adrenal hyperplasia due to 21-hydroxylase deficiency, irrespective of glucocorticoid treatment, are eligible for the inclusion in the study and may be asked to participate in the study. Patients are followed during the course of routine clinical practice for the duration of time that the study is active.
ARM1: Conventional glucocorticoid therapy is continued as before entering the study
ARM2: Dual release hydrocortisone oral tablets is administered once-daily in the fasting state. The dose is kept the same as patients had before entering the trial.
- Conditions
- Congenital Adrenal Hyperplasia
- Being tested
- Conventional Glucocorticoids (immediate release hydrocortisone, cortisone acetate, prednisone, prednisolone, dexamethasone), Dual release hydrocortisone (plenadren)
- Keywords
- congenital adrenal hyperplasia, glucocorticoid treatment, dual release hydrocortisone
- Medical subject headings
- Adrenal Hyperplasia, Congenital
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Conventional Glucocorticoids (immediate release hydrocortisone, cortisone acetate, prednisone, prednisolone, dexamethasone)Drug
Treatment of congenital adrenal hyperplasia
Dual release hydrocortisone (plenadren)Drug
Treatment of congenital adrenal hyperplasia
| Study group | Role | What they receive |
|---|---|---|
| Dual-release hydrocortisone | Experimental | Not described Receives: Drug: Conventional Glucocorticoids (immediate release hydrocortisone, cortisone acetate, prednisone, prednisolone, dexamethasone); Drug: Dual release hydrocortisone (plenadren) |
| Conventional glucocorticoids | Active comparator | Not described Receives: Drug: Conventional Glucocorticoids (immediate release hydrocortisone, cortisone acetate, prednisone, prednisolone, dexamethasone) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change from baseline in measurement of total and LDL cholesterol (mg/dl)
Single outcome measurement of cholesterol levels (mg/dl)
Measured: 0, + 6 months, + 12 months, +24 months
Secondary outcomes (16)
Change from baseline in measurement of glycaemia (mg/dl)
Measure of glycaemia (mg/dl)
Measured: 0, + 6 months, + 12 months, +24 months
Change from baseline in measurement of BMI (Kg/m2)
Measure of BMI (Kg/m2)
Measured: 0, + 6 months, + 12 months, +24 months
Change from baseline in measurement of blood pressure (mmHg)
Measure of blood pressure (mmHg)
Measured: 0, + 6 months, + 12 months, +24 months
Change from baseline in measurement of insulinemia (μU/mL)
Measure of insulinemia (μU/mL)
Measured: 0, + 6 months, + 12 months, +24 months
Change from baseline in measurement of triglycerides (mg/dl)
Measure of triglycerides (mg/dl)
Measured: 0, + 6 months, + 12 months, +24 months
Change from baseline in measurement of HDL-cholesterol (mg/dl)
Measure of HDL-cholesterol (mg/dl)
Measured: 0, + 6 months, + 12 months, +24 months
Change from baseline in measurement of Glycated Haemoglobin (%)
Measure of Glycated Haemoglobin (%)
Measured: 0, + 6 months, + 12 months, +24 months
Changes in bone mineral density
Bone mineral density quantified by Dual X-Ray Absorptiometry (DEXA)]
Measured: 0, + 12 months, +24 months
Changes in quality of life
Quality of life will be measured by Addison Quality of Life (AddiQol) questionnaire, used to assess quality of life in patients suffering from adrenal insufficiency. Each question has a score ranging from 1 to 4. Total score (minimum: 30; maximum: 120) is obtained summing each question score. The higher the scores are, the better the quality of life is. No clear cut-offs are defined.
Measured: 0, + 6 months, + 12 months, +24 months
Changes in sex function in males
Sex function will be measured by International Index of Erectile Function (IIEF) questionnaire. IIEF is divided into five function domains: Erectile function (Q1-5, Q15; score range Q1-5: 0-5; score range Q15: 1-5), Orgasmic function (Q9-10; score range Q9: 0-5; score range Q10: 1-5), Sexual desire (Q11-12; score range: 1-5), Intercourse satisfaction (Q6-8; score range: 0-5), Overall satisfaction (Q13-14; score range: 1-5). The higher the domain scores are, the better the male sexual functions are.
Measured: 0, + 6 months, + 12 months, +24 months
Changes in sex function in females
Sex function will be measured by Female Sexual Function Index (FSFI) questionnaire. FSFI is divided into six domains: Desire (Q1-2; score range: 1-5), Arousal (Q3-6; score range: 0-5), Lubrification (Q7-10; score range: 0-5), Orgasm (Q11-13; score range: 0-5), Satisfaction (Q14-16; score range Q14: 0-5; score range Q15-16: 1-5), Pain (Q17-19; score range: 0-5). To obtain the full scale score (ranging from 2 to 36), each domain score range should be corrected by an individual factor (Desire: 0.6; Arousal and Lubrification: 0.3; Orgasm, Satisfaction and Pain: 0.4). The higher the score is, the better the female sexual function is.
Measured: 0, + 6 months, + 12 months, +24 months
Changes in depression status
Depression status will be measured by Beck Depression Inventory Test (BDI-II) questionnaire. Each question has a score ranging from 0 to 3. Total score (minimum: 0; maximum: 63) is obtained summing each question score. Scores range from minimum (0-13), mild (14-19), moderate (20-28), severe (29-63)
Measured: 0, + 6 months, + 12 months, +24 months
Incidence of Treatment Adverse Events (safety analysis)
Number of participants with treatment-related adverse events as assessed by Common Terminology Criteria for Adverse Events version 4.0 (not a scale)
Measured: 0, + 6 months, + 12 months, +24 months
Changes in androgens levels
Measure of androstenedione/testosterone ratio
Measured: 0, + 6 months, + 12 months, +24 months
Changes in sperm concentration
Evaluation of sperm concentration according to WHO criteria
Measured: 0, + 6 months, + 12 months, +24 months
Changes in ovarian follicles reserve
Evaluation of number of ovarian follicles by conventional ultrasound imaging
Measured: 0, + 6 months, + 12 months, +24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Nov 2018
- Study start11 Aug 2016
- Primary completion31 Dec 2026 (estimated)
- Study completion31 Dec 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Congenital Adrenal HyperplasiaStudies of the same condition, open and under way.
- More trials run by Federico II UniversityThe sponsor's other registered studies.
- 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 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 150 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Federico II University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Prof. Rosario Pivonello, Federico II University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03760835
- Sponsor's protocol ID
- 140/16
- Acronym
- CareOnTIME
- Status last verified
- Aug 2025
- First submitted
- 9 Nov 2018
- Last updated
- 16 Sep 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 16 Sep 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Congenital Adrenal Hyperplasia: Innovative Once Daily Dual Release Hydrocortisone Treatment
- ClinicalTrials.gov ID
- NCT03760835
- Acronym / sponsor ID
- CareOnTIME / 140/16
- Conditions
- Congenital Adrenal Hyperplasia
- Keywords
- congenital adrenal hyperplasia, glucocorticoid treatment, dual release hydrocortisone
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 150 participants (estimated)
- Lead sponsor
- Federico II UniversityUniversity, hospital or other
- Study start
- 11 Aug 2016 (actual)
- Primary completion
- 31 Dec 2026 (estimated)
- Study completion
- 31 Dec 2027 (estimated)
- First posted
- 30 Nov 2018 (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.
This is a controlled, open study designed to compare the effects of dual-release hydrocortisone preparations versus conventional glucocorticoid therapy on clinical, anthropometric parameters, metabolic syndrome, hormonal profile, bone status, quality of life, reproductive, sexual and psychological functions and treatment compliance in patients affected by congenital adrenal hyperplasia due to 21 OH deficiency.
Detailed description
Congenital adrenal hyperplasia due to 21-hydroxylase deficiency is an autosomal recessive disorder characterized by cortisol and in some cases aldosterone deficiency, associated with androgen excess. Treatment goals are to replace cortisol deficiency, to control androgen levels, while avoiding the adverse effects of exogenous glucocorticoids. A variety of glucocorticoid treatments have been used in an attempt to control the overnight increase in adrenal androgens. However, there is no consensus on the optimum management of congenital adrenal hyperplasia adults. Current evidence in patients with adrenal insufficiency suggests that the inability of current regimens to replace physiological circadian cortisol levels, leads to adverse clinical outcomes, including metabolic syndrome, insulin resistance, increased risk factors for cardiovascular diseases, bone and immune alterations, sleep disturbances and quality of life impairment. Moreover, the risk for poor treatment compliance, in case of multiple daily doses treatment regimens, should not be excluded. In this trial a dual-release hydrocortisone preparation, that been able to mimic the circadian pattern of circulating cortisol, was studied in patients with adrenal insufficiency due to congenital adrenal hyperplasia.
All patients with a diagnosis of congenital adrenal hyperplasia due to 21-hydroxylase deficiency, irrespective of glucocorticoid treatment, are eligible for the inclusion in the study and may be asked to participate in the study. Patients are followed during the course of routine clinical practice for the duration of time that the study is active.
ARM1: Conventional glucocorticoid therapy is continued as before entering the study
ARM2: Dual release hydrocortisone oral tablets is administered once-daily in the fasting state. The dose is kept the same as patients had before entering the trial.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Dual-release hydrocortisone | Experimental | Drug: Conventional Glucocorticoids (immediate release hydrocortisone, cortisone acetate, prednisone, prednisolone, dexamethasone), Drug: Dual release hydrocortisone (plenadren) |
| Conventional glucocorticoids | Active comparator | Drug: Conventional Glucocorticoids (immediate release hydrocortisone, cortisone acetate, prednisone, prednisolone, dexamethasone) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- males and females aged >18 years;
- established diagnosis of adrenal insufficiency in congenital adrenal hyperplasia due to 21-hydroxylase deficiency;
- stably treated with conventional glucocorticoids, available to change their regimen according to random allocation
- written informed consent/assent to participate in the study in compliance with local regulations.
Key exclusion criteria (8 listed)
- clinical or laboratory signs of severe cerebral, respiratory, hepatobiliary or pancreatic diseases, renal dysfunction, gastrointestinal emptying, or motility disturbances (i.e. chronic diarrhea), significant psychiatric illnesses;
- history of/or current alcohol and/or drug abuse;
- night shift workers;
- underlying diseases that could necessitate treatment with glucocorticoids;
- therapies with hepatic enzyme induction drugs interfering with glucocorticoid kinetics, or immunosuppressive steroid therapy;
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 |
|---|---|---|
| Conventional Glucocorticoids (immediate release hydrocortisone, cortisone acetate, prednisone, prednisolone, dexamethasone)Treatment of congenital adrenal hyperplasia | Drug | Conventional glucocorticoids, Dual-release hydrocortisone |
| Dual release hydrocortisone (plenadren)Treatment of congenital adrenal hyperplasia | Drug | Dual-release hydrocortisone |
Primary outcome
Change from baseline in measurement of total and LDL cholesterol (mg/dl)
Time frame: 0, + 6 months, + 12 months, +24 months
Single outcome measurement of cholesterol levels (mg/dl)
16 secondary outcomes
Change from baseline in measurement of glycaemia (mg/dl)
Time frame: 0, + 6 months, + 12 months, +24 months
Change from baseline in measurement of BMI (Kg/m2)
Time frame: 0, + 6 months, + 12 months, +24 months
Change from baseline in measurement of blood pressure (mmHg)
Time frame: 0, + 6 months, + 12 months, +24 months
Change from baseline in measurement of insulinemia (μU/mL)
Time frame: 0, + 6 months, + 12 months, +24 months
Change from baseline in measurement of triglycerides (mg/dl)
Time frame: 0, + 6 months, + 12 months, +24 months
Change from baseline in measurement of HDL-cholesterol (mg/dl)
Time frame: 0, + 6 months, + 12 months, +24 months
Change from baseline in measurement of Glycated Haemoglobin (%)
Time frame: 0, + 6 months, + 12 months, +24 months
Changes in bone mineral density
Time frame: 0, + 12 months, +24 months
Changes in quality of life
Time frame: 0, + 6 months, + 12 months, +24 months
Changes in sex function in males
Time frame: 0, + 6 months, + 12 months, +24 months
Changes in sex function in females
Time frame: 0, + 6 months, + 12 months, +24 months
Changes in depression status
Time frame: 0, + 6 months, + 12 months, +24 months
Incidence of Treatment Adverse Events (safety analysis)
Time frame: 0, + 6 months, + 12 months, +24 months
Changes in androgens levels
Time frame: 0, + 6 months, + 12 months, +24 months
Changes in sperm concentration
Time frame: 0, + 6 months, + 12 months, +24 months
Changes in ovarian follicles reserve
Time frame: 0, + 6 months, + 12 months, +24 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Sep 2025.
- Individual participant dataSharing planned: No
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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.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Conventional Glucocorticoids (immediate release hydrocortisone, cortisone acetate, prednisone, prednisolone, dexamethasone) and Dual release hydrocortisone (plenadren) in people with Congenital Adrenal Hyperplasia, run by Federico II University at 1 site in Italy.
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 4 inclusion and 8 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: looking for participants now, as of the sponsor's last update on 16 Sep 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Rosario Pivonello, M.D., PhD, Professor (+390817464983, rosario.pivonello@unina.it), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change from baseline in measurement of total and LDL cholesterol (mg/dl) (time frame: 0, + 6 months, + 12 months, +24 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 16 Sep 2025.