Congenital Adrenal Hyperplasia: Innovative Once Daily Dual Release Hydrocortisone Treatment
试验速览
- 阶段
- 4 期
- 状态
- 招募中
- 发起方
- 入组人数
- 150
- 试验地点
- 1
- 主要终点
- Change from baseline in measurement of total and LDL cholesterol (mg/dl)
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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
研究组 & 干预措施
Dual-release hydrocortisone
干预措施: Conventional Glucocorticoids (immediate release hydrocortisone, cortisone acetate, prednisone, prednisolone, dexamethasone) (Drug)
Dual-release hydrocortisone
干预措施: Dual release hydrocortisone (plenadren) (Drug)
Conventional glucocorticoids
干预措施: Conventional Glucocorticoids (immediate release hydrocortisone, cortisone acetate, prednisone, prednisolone, dexamethasone) (Drug)
结局指标
主要结局
Change from baseline in measurement of total and LDL cholesterol (mg/dl)
时间窗: 0, + 6 months, + 12 months, +24 months
Single outcome measurement of cholesterol levels (mg/dl)
次要结局
- Change from baseline in measurement of HDL-cholesterol (mg/dl)(0, + 6 months, + 12 months, +24 months)
- Change from baseline in measurement of Glycated Haemoglobin (%)(0, + 6 months, + 12 months, +24 months)
- Change from baseline in measurement of insulinemia (μU/mL)(0, + 6 months, + 12 months, +24 months)
- Change from baseline in measurement of glycaemia (mg/dl)(0, + 6 months, + 12 months, +24 months)
- Change from baseline in measurement of BMI (Kg/m2)(0, + 6 months, + 12 months, +24 months)
- Change from baseline in measurement of blood pressure (mmHg)(0, + 6 months, + 12 months, +24 months)
- Change from baseline in measurement of triglycerides (mg/dl)(0, + 6 months, + 12 months, +24 months)
- Changes in bone mineral density(0, + 12 months, +24 months)
- Changes in quality of life(0, + 6 months, + 12 months, +24 months)
- Incidence of Treatment Adverse Events (safety analysis)(0, + 6 months, + 12 months, +24 months)
- Changes in androgens levels(0, + 6 months, + 12 months, +24 months)
- Changes in sperm concentration(0, + 6 months, + 12 months, +24 months)
- Changes in ovarian follicles reserve(0, + 6 months, + 12 months, +24 months)
- Changes in sex function in males(0, + 6 months, + 12 months, +24 months)
- Changes in depression status(0, + 6 months, + 12 months, +24 months)
- Changes in sex function in females(0, + 6 months, + 12 months, +24 months)
研究者
Prof. Rosario Pivonello
Full Professor
Federico II University