An Bioequivalence Study of Prednisolone and Dexamethasone; Corticosteroids Revised - The CORE Study
试验速览
- 阶段
- 1 期
- 入组人数
- 24
- 试验地点
- 1
- 主要终点
- Suppression of the hypothalamic-pituitary-adrenal axis - low dose
研究概览
简要总结
The purpose of this study is to compare two different glucocorticoids, prednisolone and dexamethasone at two different doses for their organ specific effects, utilizing modern day standards.
详细描述
Study design: A randomised, double blind, cross-over clinical trial.
Study population: healthy human adult volunteers including 12 males and 12 females aged 18-75 years old.
Intervention: In random order, subjects will receive 7,5 mg prednisolone for one week, directly followed by 30 mg of prednisolone for one week. After a washout period of 4 weeks (or by exception 8 weeks), subjects will receive 1,125 mg dexamethasone for one week, directly followed by 4,5 mg dexamethasone for one week.
Main study parameters/endpoints: The main study endpoint is the difference in total urinary cortisol excretion as measured in 24h-urine between the lower doses of prednisolone and dexamethasone as well as between the higher doses of prednisolone and dexamethasone.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Other
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Participants must be healthy with no relevant medical history and no use of medication.
- •Female participants aged <50 years must be using oral contraceptives and female participants age ≥50 years must be in the postmenopausal state
- •Command of the Dutch language
- •Providing written IC
- •BMI between 18.5 and 30 kg/m2
- •Participants must be between 18 and 75 years of age
排除标准
- •Potential participants who are unlikely to adhere to the study protocol (for instance subjects which have a history of substance abuse or non-compliance)
- •Potential participants with a medical history of:
- •Diseases affecting the HPA-axis: e.g. primary and secondary adrenal insufficiency, pituitary tumors, and nightshift workers
- •Diseases affecting the HPG-axis: e.g. Cushing disease.
- •Chronic inflammatory diseases: e.g. rheumatoid arthritis, polymyalgia rheumatic, and asthma
- •Psychiatric diseases
- •Shift workers
- •Potential participants with a kidney function <60 ml/min/1.73m2, abnormalities in liver enzymes, and/or abnormalities in thyroid function
- •Potential participants who are dependent on corticosteroids, e.g. asthmatic patients, and transplant recipients
研究组 & 干预措施
Prednisolone-Dexamethasone
Participants will receive 1 week of low dose (7,5 mg) prednisolone directly followed by 1 week of high dose prednisolone (30 mg). After a wash-out period, participants in this arm will receive 1 week of low dose dexamethasone (1,125 mg) directly followed by 1 week of high dose dexamethasone (4,5 mg).
干预措施: Dexamethasone (Drug)
Prednisolone-Dexamethasone
Participants will receive 1 week of low dose (7,5 mg) prednisolone directly followed by 1 week of high dose prednisolone (30 mg). After a wash-out period, participants in this arm will receive 1 week of low dose dexamethasone (1,125 mg) directly followed by 1 week of high dose dexamethasone (4,5 mg).
干预措施: Prednisolone (Drug)
Dexamethasone-Prednisolone
Participants will receive 1 week of low dose (1,125 mg) dexamethasone directly followed by 1 week of high dose dexamethasone (30 mg). After a wash-out period, participants in this arm will receive 1 week of low dose prednisolone (7,5 mg) directly followed by 1 week of high dose prednisolone (30 mg).
干预措施: Dexamethasone (Drug)
Dexamethasone-Prednisolone
Participants will receive 1 week of low dose (1,125 mg) dexamethasone directly followed by 1 week of high dose dexamethasone (30 mg). After a wash-out period, participants in this arm will receive 1 week of low dose prednisolone (7,5 mg) directly followed by 1 week of high dose prednisolone (30 mg).
干预措施: Prednisolone (Drug)
结局指标
主要结局
Suppression of the hypothalamic-pituitary-adrenal axis - low dose
时间窗: 1 week per treatment
Difference in HPA-axis suppression as measured by the difference of total urinary cortisol excretion in 24h-urine between 7,5 mg prednisolone and 1,125 mg dexamethasone
Suppression of the hypothalamic-pituitary-adrenal axis - high dose
时间窗: 1 week per treatment
Difference of total urinary cortisol excretion in 24h-urine between 30 mg prednisolone (preceded by 7,5 mg prednisolone for one week) and 4,5 mg dexamethasone (preceded by 1,125 mg dexamethasone for one week)
次要结局
- Suppression of the immune system - PBMCs(1 week per treatment)
- Effect on the Renin-angiotensin-aldosterone system - plasma renin(1 week per treatment)
- Effect on the Renin-angiotensin-aldosterone system - aldosterone(1 week per treatment)
- Suppression of the immune system - granulocyte count(1 week per treatment)
- Changes in hypothalamic-pituitary-adrenal axis suppression - 1(1 week per treatment)
- Changes in hypothalamic-pituitary-adrenal axis suppression - 2(1 week per treatment)
- Suppression of the hypothalamic-pituitary-adrenal axis - plasma cortisol(1 week per treatment)
- Suppression of the hypothalamic-pituitary-adrenal axis - metabolites of the 24h-urine steroid profile(1 week per treatment)
- Pharmacokinetics(1 week per treatment)
- Effect on blood pressure(1 week per treatment)
- Suppression of the hypothalamic-pituitary-adrenal axis - ACTH(1 week per treatment)
- Suppression of the hypothalamic-pituitary-gonadal axis - metabolites of the 24h-urine steroid profile(1 week per treatment)
- Clinical parameters - Weight(1 week per treatment)
- Clinical parameters - Body Mass Index (BMI)(1 week per treatment)
- Clinical parameters - Waist circumference(1 week per treatment)
- Clinical parameters - Hip circumference(1 week per treatment)
- Questionnaires - Quality of life(1 week per treatment)
- Suppression of the hypothalamic-pituitary-gonadal axis - androgen profile(1 week per treatment)
- Suppression of the hypothalamic-pituitary-gonadal axis - gonadotropins(1 week per treatment)
- Muscle mass(1 week per treatment)
- Muscle strength(1 week per treatment)
- Effect on the Renin-angiotensin-aldosterone system - plasma potassium(1 week per treatment)
- Effect on the Renin-angiotensin-aldosterone system - 24h-urine potassium(1 week per treatment)
- Effect on the Renin-angiotensin-aldosterone system - trans-tubular potassium gradient(1 week per treatment)
- Metabolic parameters - OGTT(1 week per treatment)
- Metabolic parameters - lipid profile(1 week per treatment)
- Metabolic parameters - NEFAs(1 week per treatment)
- (Serious) Adverse Events(1 week per treatment)
研究者
A.P. van Beek, MD PhD
Dr. A.P. van Beek, Endocrinologist, Principal Investigator
University Medical Center Groningen