In Vivo Study of Interactions Between the Endocannabinoid System and the Corticotropic Axis in Man
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 40
- 试验地点
- 2
- 主要终点
- Fluctuations of 2-AG (2-arachidonoyl-Glycérol) plasma concentration in relationship to cortisol plasma concentration in obese arm compare to hypercortisolism arm.
研究概览
简要总结
Working hypothesis: the interactions between the endogenous endocannabinoïds (ECS) - and cortisol, the end product of the Hypothalamo-Pituitary-Adrenal (HPA) axis may play a role in the pathophysiology of Cushing's syndrome.
The investigators speculate that:
- acute or chronic variations in plasma cortisol may induce changes in the activity of the ECS
- that there is a circadian rhythm of the ECS driven by the rythm of plasma cortisol
详细描述
The study aim to identify the relationship between the ECS and the HPA axis in humans with a main objective to assess if Cushing's syndrome induces changes in the ECS activity.
For this purpose:
- the investigors will compare plasma levels of ECS between obese controls and patients with Cushing's syndrome
- the investigors will compare plasma levels of ECS in patients with Cushing's syndrome before and immediately after curative surgery
- the investigors will compare plasma levels of ECS in patients with hypoadrenalism before and after the intake of substitutive doses of hydrocortisone
- the investigors will evaluate the plasma levels of ECS during a short synacthen test in healthy subjects.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 主要目的
- Other
- 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
- •For all patients groups:
- •Age ≥ 18,
- •Social security.
- •" Hypercortisolism " group:
- •18 < BMI < 40 kg/m2,
- •Cushing's syndrome in front of :
- •impaired 1 mg dexamethasone test (08:00 A.M. cortisol > 50 nmol/L)
- •qualitative and quantitative disrupted circadian rhythm of cortisol with increased plasma concentrations
- •free urinary cortisol upper normal range (90 µg/24H),
- •Hypercortisolism that can be treated with surgery (adrenal adenoma treated with adrenalectomy or Cushing disease treated with pituitary surgery).
- •" Obese " group:
- •Obese patients: 30 < BMI < 40 kg/m2,
- •Normal HPA axis function:
- •08:00 A.M. cortisol > 250 nmol/L and peak above 550 nmol/L after 1 mg SST,
- •Normal 24H free urinary cortisol and dexamethasone test. " Control " group:
- •Lean or overweight patients (18 < BMI < 30 kg/m2),
- •Non cortisol secreting pituitary or adrenal tumor,
- •Patient in whom a biological evaluation of the HPA axis is recommended.
- •" Hydrocortisone " group:
- •Lean or overweight patients (18 < BMI < 30 kg/m2),
- •Primary or secondary adrenal insufficiency,
- •With a need for hydrocortisone supplementation.
排除标准
- •Patients with eating disorders, major depressive disorders or psychiatric disorders other than Cushing's syndrome,
- •Cannabis consumption, alcoholism or drug addiction,
- •Active smoking,
- •cortisone treatment other than hydrocortisone,
- •Pregnancy or feeding,
- •Surgery for obesity,
- •Incapability,
- •Pathology that is life-threatening in the short term,
- •Any situation that interfere with study or is risked for patient.
研究组 & 干预措施
Obese
Subjects with BMI between 30 - 40 kg/m2 and no alteration of corticotrope axis.
干预措施: Obese (Other)
Hypercortisolism
Subject with BMI between 18 - 40 kg/m2 and presenting a hypercortisolism defined by HAS (Haute Autorité de Santé).
干预措施: Hypercortisolism (Procedure)
Control
Subject with BMI between 18 - 30 kg/m2 and with a pituitary or adrenal tumor without effect on corticotrope axis.
干预措施: Control (Other)
Hydrocortisone
Subject with BMI between 18 - 30 kg/m2 and with adrenal or corticotrope failure
干预措施: Hydrocortisone (Other)
结局指标
主要结局
Fluctuations of 2-AG (2-arachidonoyl-Glycérol) plasma concentration in relationship to cortisol plasma concentration in obese arm compare to hypercortisolism arm.
时间窗: Baseline
The primary outcome will be assessed by a measurement of plasma concentration of 2-AG during the circadian rhythm of ACTH/cortisol.
次要结局
- Measurement of plasma concentration of AEA (Anandamide), OEA (Oleoyl-EthanolAmide) and PEA (Palmitoyl-EthanolAmide) endocannabinoïds associated with variations of plasma cortisol in hypercortisolism arm(Baseline and day 6)
- Measurement of plasma concentration of AEA (Anandamide), OEA (Oleoyl-EthanolAmide) and PEA (Palmitoyl-EthanolAmide) endocannabinoïds associated with variations of plasma cortisol in hydrocortisone arm(Baseline)
- Measurement of plasma concentration of AEA (Anandamide), OEA (Oleoyl-EthanolAmide) and PEA (Palmitoyl-EthanolAmide) endocannabinoïds in control arm who have no cortisol production problem.(Baseline)