Effects of Substance P Antagonists on Adrenal Secretion

• Status: Completed
• Trial end date: 2010-06-01
• Target enrollment: 0
• Participant gender: Male

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.

• Phase: Phase 4
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: University Hospital, Rouen
• Treatments: Aprepitant; Fosaprepitant; Neurokinin A; Substance P

Criteria

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.