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Effects of Substance P Antagonists on Adrenal Secretion (APHOS)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
University Hospital, Rouen
ClinicalTrials.gov Identifier:
NCT00977223
First received: September 14, 2009
Last updated: February 14, 2012
Last verified: February 2012

September 14, 2009
February 14, 2012
June 2009
April 2010   (final data collection date for primary outcome measure)
Plasma aldosterone variation during orthostatic test [ Time Frame: Day 5 of treatment, at each period ] [ Designated as safety issue: No ]
Same as current
Complete list of historical versions of study NCT00977223 on ClinicalTrials.gov Archive Site
Basal aldosterone alteration; Aldosterone variation during metoclopramide & hypoglycaemia tests; Basal and stimulated (3 different tests) alterations of renin, cortisol & ACTH [ Time Frame: Day 4, 5 and 7 of treatment, at each period ] [ Designated as safety issue: No ]
Same as current
Not Provided
Not Provided
 
Effects of Substance P Antagonists on Adrenal Secretion
Pilot Study of the Action of the Substance P Antagonist Aprepitant on Aldosterone and Cortisol Secretion in Healthy Volunteers.

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.

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

Interventional
Phase 4
Allocation: Randomized
Endpoint Classification: Pharmacodynamics Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Healthy Volunteers
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
Other Names:
  • DCI : Aprepitant
  • Brand name : Emend
  • Experimental: Aprepitant
    7 days treatment with study drug, order of periods (active treatment or placebo) being sorted out.
    Intervention: Drug: aprepitant/placebo
  • Placebo Comparator: placebo
    7 days treatment with study drug, order of periods (active treatment or placebo) being sorted out.
    Intervention: Drug: aprepitant/placebo
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
20
June 2010
April 2010   (final data collection date for primary outcome measure)

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.
Male
18 Years to 30 Years
Yes
Contact information is only displayed when the study is recruiting subjects
France
 
NCT00977223
2007/049/HP, 2008-003367-40
No
University Hospital, Rouen
University Hospital, Rouen
Not Provided
Principal Investigator: Hervé Lefebvre, PHD Rouen University Hospital
University Hospital, Rouen
February 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP