Effects of Substance P Antagonists on Adrenal Secretion (APHOS)

February 14, 2012 updated by: University Hospital, Rouen

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 Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
20

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • France
    • Haute Normandie
      • Rouen, Haute Normandie, France, 76031
        • Rouen Clinical research Centre (CIC 0204)

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 30 years (Adult)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

Male

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Time Frame
Plasma aldosterone variation during orthostatic test
Time Frame: Day 5 of treatment, at each period
Day 5 of treatment, at each period

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Time Frame
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
Day 4, 5 and 7 of treatment, at each period

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
University Hospital, Rouen

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Hervé Lefebvre, PHD, Rouen University Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
June 1, 2009

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
April 1, 2010

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
June 1, 2010

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
September 14, 2009

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 14, 2009

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
September 15, 2009

Study Record Updates

Last Update Posted (Estimate)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
February 16, 2012

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
February 14, 2012

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
February 1, 2012

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 2007/049/HP
  • 2008-003367-40 (EudraCT Number)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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