Effects of Substance P Antagonists on Adrenal Secretion

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

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.