Clinical trial NCT03760835: Congenital Adrenal Hyperplasia Once Daily Hydrocortisone Treatment
Official title: Congenital Adrenal Hyperplasia: Innovative Once Daily Dual Release Hydrocortisone Treatment
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Congenital Adrenal Hyperplasia
Keywords: congenital adrenal hyperplasia
glucocorticoid treatment
dual release hydrocortisone
Lead sponsor: Federico II University
Sponsor class: OTHER
First posted: 2018-11-30
Enrollment: 150
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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 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.

Eligibility criteria: Inclusion Criteria:

* 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.

Exclusion Criteria:

* 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

Primary outcomes:
measure: Change from baseline in measurement of total and LDL cholesterol (mg/dl)
timeFrame: 0, + 6 months, + 12 months, +24 months
Secondary outcomes:
measure: Change from baseline in measurement of glycaemia (mg/dl)
timeFrame: 0, + 6 months, + 12 months, +24 months
measure: Change from baseline in measurement of BMI (Kg/m2)
timeFrame: 0, + 6 months, + 12 months, +24 months
measure: Change from baseline in measurement of blood pressure (mmHg)
timeFrame: 0, + 6 months, + 12 months, +24 months
measure: Change from baseline in measurement of insulinemia (μU/mL)
timeFrame: 0, + 6 months, + 12 months, +24 months
measure: Change from baseline in measurement of triglycerides (mg/dl)
timeFrame: 0, + 6 months, + 12 months, +24 months
measure: Change from baseline in measurement of HDL-cholesterol (mg/dl)
timeFrame: 0, + 6 months, + 12 months, +24 months
measure: Change from baseline in measurement of Glycated Haemoglobin (%)
timeFrame: 0, + 6 months, + 12 months, +24 months
measure: Changes in bone mineral density
timeFrame: 0, + 12 months, +24 months
measure: Changes in quality of life
timeFrame: 0, + 6 months, + 12 months, +24 months
measure: Changes in sex function in males
timeFrame: 0, + 6 months, + 12 months, +24 months
measure: Changes in sex function in females
timeFrame: 0, + 6 months, + 12 months, +24 months
measure: Changes in depression status
timeFrame: 0, + 6 months, + 12 months, +24 months
measure: Changes in treatment compliance
timeFrame: 0, + 6 months, + 12 months, +24 months
measure: Incidence of Treatment Adverse Events (safety analysis)
timeFrame: 0, + 6 months, + 12 months, +24 months
measure: Changes in androgens levels
timeFrame: 0, + 6 months, + 12 months, +24 months
measure: Changes in sperm concentration
timeFrame: 0, + 6 months, + 12 months, +24 months
measure: Changes in ovarian follicles reserve
timeFrame: 0, + 6 months, + 12 months, +24 months
Other outcomes:
Locations:
city: Naples
country: Italy
facility: Federico II University
Study officials:
References: