Pilot Study of Aprepitant Effect on Aldosterone Secretion in Diabetic Patient (Diabetes Mellitus) With Hypertension Associated With Low Renin
概览
- 阶段
- 2 期
- 干预措施
- Blood sampling
- 疾病 / 适应症
- Type 2 Diabetes
- 发起方
- University Hospital, Rouen
- 入组人数
- 5
- 试验地点
- 1
- 主要终点
- Difference from baseline in Plasma aldosterone concentration
- 状态
- 已完成
- 最后更新
- 上个月
概览
简要总结
Aldosterone regulation is mediated by hormonal control, and nervous control. Autonomic nervous system action could be mediated by neuropeptides in the adrenal gland. Therefore, in pathological conditions and especially in diabetes, low-renin hypertension with normal or high plasma aldosterone could be caused by sympathetic nervous system hypertonia.
Data from the literature and previous in vitro research conducted in the investigators' laboratory (INSERM U982, University of Rouen) suggest that adrenal corticosteroid secretion might be controlled by sympathetic nervous system. This neurocrine regulation of corticosteroid secretion involves locally released neuropeptides. Among them, substance P is able to stimulate aldosterone and cortisol production via NK1 receptors. A previous clinical trial conducted at the University Hospital of Rouen, APHOS (NCT00977223) studied the effects of a NK1 receptor antagonist, aprepitant, on adrenocortical secretions in healthy volunteers.
The aim of the present study is to investigate the effects of a NK1 receptor antagonist, aprepitant, on adrenocortical secretions in volunteers with diabetes associated with low-renin hypertension. Aprepitant is a drug already available for the treatment of nausea induced by chemotherapy.
In the present phase II trial, plasma aldosterone and cortisol levels will be measured under treatment with aprepitant versus placebo, in both basal conditions and after activation of the adrenocortical function by upright posture. All volunteers will be given the two substances (aprepitant and placebo) in a random order during two 14 day-periods separated by a 21 day-wash-out.
This study should allow to determine the role of substance P in the control of corticosteroid production in human with diabetes, associated with a low-renin hypertension.
研究者
入排标准
入选标准
- •Male or menopausal female subjects;
- •Age ranging 18-30 years old;
- •Submitted to a social security regimen;
- •Agreeing to the study \& Informed consent form signed;
- •Body mass index (\[weight (kg)/height (m)\]²) \< 27;
- •No treatment received 6 weeks before inclusion;
- •No anomaly after: complete clinical examination, pulse and blood pressure measurement, ECG;
- •No biological abnormality after the following biological testing:
- •Hematology: white \& red blood cells \& platelets count, haemoglobin, hematocrit, Blood biochemistry: sodium, potassium, chloride, bicarbonate, creatinine, urea, Urinary biochemistry (24 h collection): cortisol, aldosterone, Serologies: HIV, HBV, HCV,
- •No participation in a clinical trial 3 months ago before inclusion,
排除标准
- •Female subject potentially pregnant,
- •Subject younger than 18 year-old and older than 70 year-old,
- •Subject without diabetes condition or with diabetes but normal blood pressure (below 130/80 mmHg),
- •Subject with glycated hemoglobin HbA1c \< 6.5% or \>11%,
- •Subject with leuconeutropenia (neutrophils below 1700/mm3),
- •Subject with severe medical or surgical history,
- •Patients treated with drugs metabolized by CYP3A4 and CYP2C9: corticosteroids, vitamin K , hormonal contraceptives, tolbutamide, benzodiazepines, derived from ergot, antiepileptics, hypericum, macrolides, azole antifungals.
- •Patients treated with drugs interfering with the renin-angiotensin- aldosterone system : beta-blockers, diuretics , anti -aldosterone drugs , direct renin inhibitors , insulin,
- •type 2 diabetes patients with a vegetative autonomic neuropathy,
- •Patients with adrenal mass was diagnosed at imaging,
研究组 & 干预措施
Administration of Aprepitant
Administration of Aprepitant 80 mg once per day during 14 days; Blood sampling, electrocardiogram, orthostatic test and Blood Pressure Measurement are done after 14 days
干预措施: Blood sampling
Administration of Aprepitant
Administration of Aprepitant 80 mg once per day during 14 days; Blood sampling, electrocardiogram, orthostatic test and Blood Pressure Measurement are done after 14 days
干预措施: Blood Pressure Measurement
Administration of Aprepitant
Administration of Aprepitant 80 mg once per day during 14 days; Blood sampling, electrocardiogram, orthostatic test and Blood Pressure Measurement are done after 14 days
干预措施: electrocardiogram
Administration of Aprepitant
Administration of Aprepitant 80 mg once per day during 14 days; Blood sampling, electrocardiogram, orthostatic test and Blood Pressure Measurement are done after 14 days
干预措施: orthostatic test
Administration of Aprepitant
Administration of Aprepitant 80 mg once per day during 14 days; Blood sampling, electrocardiogram, orthostatic test and Blood Pressure Measurement are done after 14 days
干预措施: Administration of Aprepitant
Administration of placebo
Administration of Placebo once per day during 14 days; Blood sampling, electrocardiogram, orthostatic test and Blood Pressure Measurement are done after 14 days
干预措施: Blood sampling
Administration of placebo
Administration of Placebo once per day during 14 days; Blood sampling, electrocardiogram, orthostatic test and Blood Pressure Measurement are done after 14 days
干预措施: Blood Pressure Measurement
Administration of placebo
Administration of Placebo once per day during 14 days; Blood sampling, electrocardiogram, orthostatic test and Blood Pressure Measurement are done after 14 days
干预措施: electrocardiogram
Administration of placebo
Administration of Placebo once per day during 14 days; Blood sampling, electrocardiogram, orthostatic test and Blood Pressure Measurement are done after 14 days
干预措施: orthostatic test
Administration of placebo
Administration of Placebo once per day during 14 days; Blood sampling, electrocardiogram, orthostatic test and Blood Pressure Measurement are done after 14 days
干预措施: Administration of placebo
结局指标
主要结局
Difference from baseline in Plasma aldosterone concentration
时间窗: Baseline and Day 14
Plasma aldosterone concentration is analyzed
次要结局
- Difference from baseline in HOMA index(Baseline and Day 14)
- Difference from baseline in Plasma cortisol(Baseline and Day 14)
- Difference from baseline in plasma renin(Baseline and Day 14)
- Difference from baseline in blood electrolytes measurement(Baseline and Day 14)