CompletedPhase 2

Pilot Study of Aprepitant Effect on Aldosterone Secretion in Diabetic Patient (Diabetes Mellitus) With Hypertension Associated With Low Renin

France5 participantsStarted 2017-07-13

Plain-language summary

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.

Who can participate

Age range18 Years

SexALL

See this in plain English?

AI-rewrites the medical criteria so a patient or caregiver can understand them. Always confirm with the trial site.

Inclusion Criteria: * 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, * Subscription to national social security, * Signed informed consent. Exclusion Criteria: * 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 dr…

What they're measuring

Difference from baseline in Plasma aldosterone concentration

Timeframe: Baseline and Day 14

Trial details

NCT IDNCT02811055

SponsorUniversity Hospital, Rouen

Sponsor typeOTHER

Study typeINTERVENTIONAL

Primary completion2020-12-05