Congenital Adrenal Hyperplasia Once Daily Hydrocortisone Treatment
- Conditions
- Congenital Adrenal Hyperplasia
- Interventions
- Registration Number
- NCT03760835
- Lead Sponsor
- Federico II University
- 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.
Recruitment & Eligibility
- Status
- UNKNOWN
- Sex
- All
- Target Recruitment
- 150
- 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.
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Dual-release hydrocortisone Conventional Glucocorticoids (immediate release hydrocortisone, cortisone acetate, prednisone, prednisolone, dexamethasone) - Dual-release hydrocortisone Dual release hydrocortisone (plenadren) - Conventional glucocorticoids Conventional Glucocorticoids (immediate release hydrocortisone, cortisone acetate, prednisone, prednisolone, dexamethasone) -
- Primary Outcome Measures
Name Time Method Change from baseline in measurement of total and LDL cholesterol (mg/dl) 0, + 6 months, + 12 months, +24 months Single outcome measurement of cholesterol levels (mg/dl)
- Secondary Outcome Measures
Name Time Method Changes in sex function in males 0, + 6 months, + 12 months, +24 months 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.
Change from baseline in measurement of glycaemia (mg/dl) 0, + 6 months, + 12 months, +24 months Measure of glycaemia (mg/dl)
Change from baseline in measurement of BMI (Kg/m2) 0, + 6 months, + 12 months, +24 months Measure of BMI (Kg/m2)
Change from baseline in measurement of triglycerides (mg/dl) 0, + 6 months, + 12 months, +24 months Measure of triglycerides (mg/dl)
Change from baseline in measurement of HDL-cholesterol (mg/dl) 0, + 6 months, + 12 months, +24 months Measure of HDL-cholesterol (mg/dl)
Changes in depression status 0, + 6 months, + 12 months, +24 months 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)
Incidence of Treatment Adverse Events (safety analysis) 0, + 6 months, + 12 months, +24 months Number of participants with treatment-related adverse events as assessed by Common Terminology Criteria for Adverse Events version 4.0 (not a scale)
Changes in androgens levels 0, + 6 months, + 12 months, +24 months Measure of androstenedione/testosterone ratio
Changes in sperm concentration 0, + 6 months, + 12 months, +24 months Evaluation of sperm concentration according to WHO criteria
Changes in treatment compliance 0, + 6 months, + 12 months, +24 months Treatment compliance will be measured by Morisky Medical Adherence Scale-8 questionnaire. Each question has a score ranging from 0 to 1. Low Adherence (\< 6); Medium Adherence (6 to \<8); High Adherence (= 8)
Changes in ovarian follicles reserve 0, + 6 months, + 12 months, +24 months Evaluation of number of ovarian follicles by conventional ultrasound imaging
Change from baseline in measurement of blood pressure (mmHg) 0, + 6 months, + 12 months, +24 months Measure of blood pressure (mmHg)
Change from baseline in measurement of insulinemia (μU/mL) 0, + 6 months, + 12 months, +24 months Measure of insulinemia (μU/mL)
Change from baseline in measurement of Glycated Haemoglobin (%) 0, + 6 months, + 12 months, +24 months Measure of Glycated Haemoglobin (%)
Changes in bone mineral density 0, + 12 months, +24 months Bone mineral density quantified by Dual X-Ray Absorptiometry (DEXA)\]
Changes in quality of life 0, + 6 months, + 12 months, +24 months 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.
Changes in sex function in females 0, + 6 months, + 12 months, +24 months 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.
Trial Locations
- Locations (1)
Federico II University
🇮🇹Naples, Italy