Effects of Substance P Antagonists on Adrenal Secretion

Healthy Volunteers Clinical Trial

— APHOS  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00977223
• Other study ID #: 2007/049/HP
• Secondary ID: 2008-003367-40
• Status: Completed
• Phase: Phase 4
• First received: September 14, 2009
• Last updated: February 14, 2012
• Start date: June 2009
• Est. completion date: June 2010

Study information

• Verified date: February 2012
• Source: University Hospital, Rouen
• Contact: n/a
• Is FDA regulated: No
• Health authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
• Study type: Interventional

Clinical Trial 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.

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 20
• Est. completion date: June 2010
• Est. primary completion date: April 2010
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 18 Years to 30 Years

Eligibility

Inclusion Criteria:

• Male 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 before inclusion.

Exclusion Criteria:

• Subject not agreeing to the study or impossible to follow-up;

• Known history of significant medical or surgical pathology, notably endocrine;

• Renal or hepatic insufficiency;

• Nephrotic syndrome;

• Edematous syndrome;

• Hypertension or postural hypotension;

• Cardiac rhythm or conduction pathologies;

• Cardiac insufficiency;

• Epilepsy;

• Significant psychiatric disorder;

• Known history of severe allergy, hypersensitivity to aprepitant ant/or metoclopramide;

• Hereditary problems of fructose intolerance, glucose-galactose malabsorption or sucrase-isomaltase deficit;

• Impaired lactose tolerance.

Study Design

Allocation: Randomized, Endpoint Classification: Pharmacodynamics Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)

Related Conditions & MeSH terms

• Healthy Volunteers

Intervention

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

Locations

Country	Name	City	State
France	Rouen Clinical research Centre (CIC 0204)	Rouen	Haute Normandie

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital, Rouen

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Plasma aldosterone variation during orthostatic test		Day 5 of treatment, at each period	No
Secondary	Basal aldosterone alteration; Aldosterone variation during metoclopramide & hypoglycaemia tests; Basal and stimulated (3 different tests) alterations of renin, cortisol & ACTH		Day 4, 5 and 7 of treatment, at each period	No