A Dose-response Study of Markers of Glucocorticoid Effects (DOSCORT): A Double-blinded, Randomized, 2-dose, Cross-over Study
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 发起方
- 入组人数
- 30
- 试验地点
- 1
- 主要终点
- Protein profile changes between physiological and supra physiological doses of betamethasone.
研究概览
简要总结
DOSCORT is a 2-dose, cross-over study primarily aiming to identify and validate novel biological markers (biomarkers) of glucocorticoid effect in the human body. Patients with Addison´s disease, primary adrenal insufficiency, with life-long glucocorticoid replacement therapy will undergo 2 treatment periods where their usual hydrocortisone treatment will be replaced with betamethasone in physiological and supra physiological doses. Blood, saliva, urine, health related Quality-of-life self-assessment forms, measurements of physical activity and sleep quality will be collected from both treatment periods.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
盲法说明
Double-blinded
入排标准
- 年龄范围
- 20 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Males and females at ages 20-65 years
- •Previously diagnosed (e.g. more than 12 months ago) with primary adrenal insufficiency due to autoimmune adrenalitis, i.e. Addison´s disease
- •A stable daily glucocorticoid replacement dose for at least 3 months prior to study entry
- •An oral glucocorticoid replacement dose of 15-30 mg Hydrocortisone total daily dose
- •If needed, a stable fludrocortisone replacement dose for at least 3 months prior to study entry
- •Body mass index (BMI) of 20-35 kg/m2
- •Ability to comply to the protocol procedures and having signed informed consent to participate in the study
排除标准
- •Clinical or laboratory signs of significant cerebral, cardiovascular, respiratory, hepaticobiliary/ pancreatic disease which in the investigators judgement may interfere with the study assessment of completion of the study
- •Clinically significant renal dysfunction with a serum creatinine above 150 mmol/L
- •Pregnant or lactating women
- •Diabetes Mellitus
- •Systemic infections
- •Regular dehydroepiandrosterone (DHEA) medication for the past 4 weeks
- •Any medication with agents which in the investigators judgement might interfere with the study drugs kinetics, including therapies affecting gastro intestinal emptying or motility
- •Alcohol/drug abuse or any other condition associated with poor patient compliance, including expected non-cooperation, as judged by the investigator
- •Hypersensitivity to the active substance or any excipients used in the study drug of choice
- •Any additional underlying disease that may need regular or periodic pharmacological treatment with glucocorticoids during the trail, such as asthma, skin- or eye conditions treated with inhaled or topical glucocorticoids
- •Any additional underlying condition that needs treatment with intramuscular or intra-articular steroid injections during the trial
研究组 & 干预措施
betamethasone - physiological dose
Replacing participants hydrocortisone with a daily dose of betamethasone in an estimated physiological dose during one treatment period.
干预措施: Betamethasone (Drug)
betamethasone - supra physiological dose
Replacing participants hydrocortisone with a daily dose of betamethasone in an estimated supra physiological dose during one treatment period.
干预措施: Betamethasone (Drug)
结局指标
主要结局
Protein profile changes between physiological and supra physiological doses of betamethasone.
时间窗: Changes in proteome (g/dl or umol/l) during 7 days of treatment with two different doses of betamethasone
By using mas spectrometry, protein profile changes in blood, urine and saliva will be identified at four timepoints: after 3 hours and after 7 days during treatment with betamethasone in a physiological dose and after 3 hours and after 7 days during treatment with betamethasone in a supra physiological dose.
Metabolite profile changes between physiological and supra physiological doses of betamethasone.
时间窗: Changes in metabolome (units depending on the kind of metabolome) during 7 days of treatment with two different doses of betamethasone
By using mas spectrometry, metabolite profile changes in blood, urine and saliva will be identified at four timepoints: after 3 hours and after 7 days during treatment with betamethasone in a physiological dose and after 3 hours and after 7 days during treatment with betamethasone in a supra physiological dose.
次要结局
- Messenger RNA (mRNA)/miRNA profile changes between physiological and supra physiological doses of betamethasone.(Changes in mRNA/miRNA (Svedberg Unit, S) during 7 days of treatment with two different doses of betamethasone)
- Changes in self-reported Quality of Life between physiological and supra physiological doses of betamethasone using the Addison-specific Quality of Life questionnaire (ADDIQoL).(Changes in units of the ADDIQoL questionnaire (units on a scale) after 7 days of treatment with two different doses of betamethasone)
- Changes in bone-markers between physiological and supra physiological doses of betamethasone.(Changes in levels of bone-markers in blood (units depending on sample analysis) during 7 days of treatment with two different doses of betamethasone)
- Changes in glucose metabolism between physiological and supra physiological doses of betamethasone.(Changes in glucose metabolism (units depending on sample analysis) during 7 days of treatment with two different doses of betamethasone)
- Changes in self-reported Quality of Life between physiological and supra physiological doses of betamethasone using the Psychological General Well-being (PGWB) index.(Changes in units of the PGWB index (units on a scale) after 7 days of treatment with two different doses of dexamethasone)
- Changes in self-reported quality of life and fatigue between physiological and supra physiological doses of betamethasone using the Fatigue impact scale (FIS)(Changes in units in the FIS (units on a scale) after 7 days of treatment with two different doses of betamethasone)
- Changes in daily physical activity between physiological and supra physiological doses of betamethasone(Changes in daily physical activity (units provided in connected software) after 7 days of treatment with two different doses of betamethasone)
- Changes in lipid-profile between physiological and supra physiological doses of betamethasone.(Changes in lipid-profile (units depending on sample analysis) during 7 days of treatment with two different doses of betamethasone)
- Changes in self-reported quality of life and fatigue between physiological and supra physiological doses of betamethasone using the Functional Outcomes of Sleep Questionnaire (FOSQ).(Changes in units in the FOSQ (units on a scale) after 7 days of treatment with two different doses of betamethasone)
- Changes in sleep quality between physiological and supra physiological doses of betamethasone(Changes in sleep quality (measurements and units provided in connected software) after 7 days of treatment with two different doses of betamethasone)