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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
History of Changes
  Purpose

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.


Condition Intervention Phase
Healthy Volunteers
 Drug: aprepitant/placebo
 Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacodynamics Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Official Title: Pilot Study of the Action of the Substance P Antagonist Aprepitant on Aldosterone and Cortisol Secretion in Healthy Volunteers.

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by University Hospital, Rouen:

Primary Outcome Measures:
  • Plasma aldosterone variation during orthostatic test [ Time Frame: Day 5 of treatment, at each period ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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 ]

Enrollment: 20
Study Start Date: June 2009
Study Completion Date: June 2010
Primary Completion Date: April 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Aprepitant
7 days treatment with study drug, order of periods (active treatment or placebo) being sorted out.
 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
Placebo Comparator: placebo
7 days treatment with study drug, order of periods (active treatment or placebo) being sorted out.
 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

Detailed 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

  Eligibility

Ages Eligible for Study:   18 Years to 30 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
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.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00977223

Locations
France
Rouen Clinical research Centre (CIC 0204)
Rouen, Haute Normandie, France, 76031
Sponsors and Collaborators
University Hospital, Rouen
Investigators
Principal Investigator: Hervé Lefebvre, PHD Rouen University Hospital
  More Information

No publications provided

Responsible Party: University Hospital, Rouen
ClinicalTrials.gov Identifier: NCT00977223     History of Changes
Other Study ID Numbers: 2007/049/HP, 2008-003367-40
Study First Received: September 14, 2009
Last Updated: February 14, 2012
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

Keywords provided by University Hospital, Rouen:
Aldosterone
Substance P
Cortisol
Aprepitant
Adrenal glands

Additional relevant MeSH terms:
Substance P
Aprepitant
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
 Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Central Nervous System Agents
Therapeutic Uses
Gastrointestinal Agents

ClinicalTrials.gov processed this record on May 19, 2013