Use of Liquorice and Grapefruit in Patients With Addison's Disease
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 17
- 试验地点
- 2
- 主要终点
- AUC Serum Cortisol - Levels of cortisol in serum during the first 2.6 hours after oral administration of cortisone acetate.
研究概览
简要总结
Addison's disease is a rare disease, wherein the adrenals can not produce sufficient steroid hormones (cortisol and aldosterone). Patients with Addison's disease report impaired subjective health status, and they have increased all-cause mortality. Conventional therapy is by oral replacement of glucocorticoid and mineralocorticoid hormones, but this strategy imperfectly mimic the diurnal cortisol variations, and render the patients both over- and under-treated. Anecdotally, some patients with adrenal insufficiency may benefit from the use of various nutritional compounds. We hypothesised that liquorice and grapefruit altered the metabolism and absorption of cortisone acetate.
详细描述
In the present study, cortisone acetate absorption and metabolism are assessed in subjects with Addison's disease on three occasions. On the first occasion, the subjects are on their regular diet, but avoid ingestion of grapefruit and liquorice. At the end of the baseline assessment the order of the nutritional compounds (liquorice-grapefruit juice or grapefruit juice-liquorice) to be investigated in the next two assessments are randomised.
On the two next occasions, the absorption and metabolism of cortisone acetate is studied when study subjects consume liquorice and grapefruit juice. Between the use of grapefruit and liquorice there is a wash out period of at least 3 weeks.
For studies on liquorice effects, the subjects ingest 24-gram liquorice per day (equivalent of 150-mg glycyrrhizinic acid per day). For studies on grapefruit juice effects, subjects drink 200-ml grapefruit juice three times a day for three days. They maintain their regular medication and usual diet.
Time-series of cortisol and cortisone are obtained in serum and saliva samples on the third day of liquorice/grapefruit juice use. 24-hour urine is also collected.
Measurements of cortisol and metabolites in serum and saliva are used to calculate pharmacokinetical parameters. The measurements from samples obtained when using the investigated nutritional compounds are compared to the baseline assessment in each subject. Metabolites in 24-hour urine are compared similarly to investigate changes in urinary excretion, and to estimate the activity of enzymes involved in the metabolism of cortisol (5alfa-reductase, 5beta-reductase, cytochrome P450 3A4 system, 11-beta hydroxysteroid dehydrogenase).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Supportive Care
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Verified diagnosis of adrenal insufficiency (Addison's disease)
- •Stable cortisone acetate replacement therapy
- •Written informed consent
排除标准
- •Malignant disease
- •Pharmacological treatment with other glucocorticoids
- •Pregnancy
- •Current minor disease (ie the flu)
- •Major disease or accident requiring hospitalization the last three months
- •Use of grapefruit juice or liquorice the last two weeks before study start
- •Blood pressure above 150mmHg systolic or 90 mmHg diastolic.
结局指标
主要结局
AUC Serum Cortisol - Levels of cortisol in serum during the first 2.6 hours after oral administration of cortisone acetate.
时间窗: Outcome measures are assessed when all subjects have completed the study, approximately 1.5-2.0 years after study start.
The area under the curve (AUC) of cortisol is calculated based on serum time-series sampling (every 20 minutes for 2.6 h after oral administration of cortisone acetate). The AUCs obtained during liquorice and grapefruit juice intakes are compared to the baseline assessment (without these nutritional compounds). All other pharmacokinetic properties (primary and secondary outcome measures) are compared analogously.
次要结局
- Urinary aTHF/THF-ratio(Outcome measures are assessed when all subjects have completed the study, approximately 1.5-2.0 years after study start.)
- Serum Cortisone levels at the end of time-series sampling (t=160min)(Outcome measures are assessed when all subjects have completed the study, approximately 1.5-2.0 years after study start.)
- Half life of serum cortisone(Outcome measures are assessed when all subjects have completed the study, approximately 1.5-2.0 years after study start.)
- Time of maximum concentration of Saliva Cortisone(Outcome measures are assessed when all subjects have completed the study, approximately 1.5-2.0 years after study start.)
- Half life of serum cortisol(Outcome measures are assessed when all subjects have completed the study, approximately 1.5-2.0 years after study start.)
- Urine total metabolites (Urinary cortisol+cortisone+6OHF+aTHF+THF+THE)(Outcome measures are assessed when all subjects have completed the study, approximately 1.5-2.0 years after study start.)
- Saliva Cortisone levels at the end of time-series sampling (t=160min)(Outcome measures are assessed when all subjects have completed the study, approximately 1.5-2.0 years after study start.)
- Time of maximum concentration of serum Cortisone(Outcome measures are assessed when all subjects have completed the study, approximately 1.5-2.0 years after study start.)
- Serum Cortisol levels at the end of time-series sampling (t=160min)(Outcome measures are assessed when all subjects have completed the study, approximately 1.5-2.0 years after study start.)
- Saliva Cortisol levels at the end of time-series sampling (t=160min)(Outcome measures are assessed when all subjects have completed the study, approximately 1.5-2.0 years after study start.)
- Time of maximum concentration of serum Cortisol(Outcome measures are assessed when all subjects have completed the study, approximately 1.5-2.0 years after study start.)
- Time of maximum concentration of Saliva Cortisol(Outcome measures are assessed when all subjects have completed the study, approximately 1.5-2.0 years after study start.)
- Urinary Ratio Cortisol/6beta-OH-Cortisol(Outcome measures are assessed when all subjects have completed the study, approximately 1.5-2.0 years after study start.)
- AUC Saliva Cortisol(Outcome measures are assessed when all subjects have completed the study, approximately 1.5-2.0 years after study start.)
- Urinary ratio (aTHF+THF)/THE(Outcome measures are assessed when all subjects have completed the study, approximately 1.5-2.0 years after study start.)
- AUC Saliva cortisone(Outcome measures are assessed when all subjects have completed the study, approximately 1.5-2.0 years after study start.)
- AUC Serum Cortisone(Outcome measures are assessed when all subjects have completed the study, approximately 1.5-2.0 years after study start.)