NCT00977223

Effects of Substance P Antagonists on Adrenal Secretion

Pilot Study of the Action of the Substance P Antagonist Aprepitant on Aldosterone and Cortisol Secretion in Healthy Volunteers.

• Status: Completed
• Phase: Phase 4
• Study type: Interventional
• Enrollment: 20 (actual)
• Sponsor: University Hospital, Rouen · Academic / Other
• Sex: Male
• Age: 18 Years – 30 Years
• Healthy volunteers: Accepted

Summary

Data from the literature and previous in vitro research conducted in the investigators' laboratory (INSERM U413/EA4310, 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. The aim of the present study is to investigate the effects of a NK1 receptor antagonist, aprepitant, on adrenocortical secretions in healthy volunteers. Aprepitant is a drug already available for the treatment of nausea induced by chemotherapy. In the present phase IV 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 various stimuli, including upright posture, metoclopramide, and insulin-induced hypoglycaemia. All healthy volunteers will be given the two substances (aprepitant and placebo) in a random order during two one-week periods separated by a 14 day-wash-out. This study should allow to determine the role of substance P in the control of corticosteroid production in normal man.

Detailed description

STUDY DESIGN Phase IV, proof of concept, interventional, monocentric, randomised, double blind, cross-over study: The effects of a substance P antagonist (Emend) on corticosteroid secretion will be compared to those of a placebo. STUDY OBJECTIVES Main objective: to verify that adrenal corticosteroid secretion is actually controlled by substance P. Secondary objective: to determine the physiological conditions that involve the control of adrenocortical function by tachykinins. NUMBER OF SUBJECTS 20 healthy volunteers ELIGIBILITY CRITERIA (see below) DURATION OF STUDY Overall duration: 13 months Inclusion period: 12 months Follow up period (for 1 subject): 5 weeks Exclusion period: 1 month ENDPOINTS PRIMARY ENDPOINT: blood aldosterone variation during orthostatic test SECONDARY ENDPOINTS Basal aldosterone alteration Aldosterone variation during metoclopramide \& hypoglycaemia tests Basal and stimulated (3 different tests) alterations of renin, cortisol \& ACTH REGULATORY AUTHORIZATIONS Ethics committee authorization: dec 18th, 2008 Regulatory authorization: march 3rd, 2009

Conditions

• Healthy Volunteers

Interventions

Type	Name	Description
DRUG	aprepitant/placebo	Aprepitant, 125 MG at day 1 then 80 MG day 2-7, once a day, per os, at 8 AM during breakfast

Timeline

• Start date: 2009-06-01
• Primary completion: 2010-04-01
• Completion: 2010-06-01
• First posted: 2009-09-15
• Last updated: 2012-02-16

Locations

1 site across 1 country: France