Effects of Substance P Antagonists on Adrenal Secretion
Condition: Healthy Volunteers
Study type: Interventional
Phase: Phase 4

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
    

Intervention name(s): aprepitant/placebo
Intervention type(s): Drug
Intervention description(s): Aprepitant, 125 MG at day 1 then 80 MG day 2-7, once a day, per os, at 8 AM during breakfast
Other intervention name(s): DCI : Aprepitant; Brand name : Emend
Intervention MeSH terms: Aprepitant; Fosaprepitant
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Keywords: Aldosterone; Substance P; Cortisol; Aprepitant; Adrenal glands