Effects of Substance P Antagonists on Adrenal Secretion

NCT00977223 | Completed Phase 4

• 2 other identifiers: 2007/049/HP2008-003367-40
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Healthy Volunteers

Keywords

Aldosterone; Substance P; Cortisol; Aprepitant; Adrenal glands

Outcome Measures

Primary Outcomes (1)

• Plasma aldosterone variation during orthostatic test

  Day 5 of treatment, at each period

Secondary Outcomes (1)

• 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

Study Arms (2)

Aprepitant

EXPERIMENTAL

7 days treatment with study drug, order of periods (active treatment or placebo) being sorted out.

Drug: aprepitant/placebo

placebo

PLACEBO COMPARATOR

7 days treatment with study drug, order of periods (active treatment or placebo) being sorted out.

Drug: aprepitant/placebo

Interventions

aprepitant/placebo DRUG

Aprepitant, 125 MG at day 1 then 80 MG day 2-7, once a day, per os, at 8 AM during breakfast

Also known as: DCI : Aprepitant, Brand name : Emend

Aprepitant; placebo

Eligibility Criteria

• Age: 18 Years - 30 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• University Hospital, Rouen: lead

Study Sites (1)

Rouen Clinical research Centre (CIC 0204)

Rouen, Haute Normandie, 76031, France

Location

Related Publications (1)

• Wils J, Duparc C, Cailleux AF, Lopez AG, Guiheneuf C, Boutelet I, Boyer HG, Dubessy C, Cherifi S, Cauliez B, Gobet F, Defortescu G, Menard JF, Louiset E, Lefebvre H. The neuropeptide substance P regulates aldosterone secretion in human adrenals. Nat Commun. 2020 May 29;11(1):2673. doi: 10.1038/s41467-020-16470-8.

  PMID: 32471973 DERIVED

MeSH Terms

Interventions

Aprepitant

Intervention Hierarchy (Ancestors)

Morpholines; Oxazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Hervé Lefebvre, PHD

  University Hospital, Rouen

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 14, 2009
• First Posted: September 15, 2009
• Study Start: June 1, 2009
• Primary Completion: April 1, 2010
• Study Completion: June 1, 2010
• Last Updated: February 16, 2012

Record last verified: 2012-02

Locations

FR (1)