Healthy VolunteersPhase 4APHOSNCT00977223
Effects of Substance P Antagonists on Adrenal Secretion
A Phase 4 study of Healthy Volunteers, run by University Hospital, Rouen at 1 site in France.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 30 years, men onlyHealthy volunteers can take part
- Conditions the study is for
- Healthy Volunteers
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 20 participants
- Where
- 1 siteFrance
- Study dates
- Jun 2009to Jun 2010
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 30 years
- Men only
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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;
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- 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.
Who cannot join
- 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;
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- 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.
Trial locations and contacts
1 site in 1 country.
France1 site
Rouen Clinical research Centre (CIC 0204)
Rouen, Haute Normandie, 76031
About this study
Official title: 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.
Read more
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.
Read the 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
- Conditions
- Healthy Volunteers
- Being tested
- aprepitant/placebo
- Keywords
- Aldosterone, Substance P, Cortisol, Aprepitant, Adrenal glands
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
aprepitant/placeboDrug
Also called DCI : Aprepitant, Brand name : Emend
Aprepitant, 125 MG at day 1 then 80 MG day 2-7, once a day, per os, at 8 AM during breakfast
| Study group | Role | What they receive |
|---|---|---|
| Aprepitant | Experimental | 7 days treatment with study drug, order of periods (active treatment or placebo) being sorted out. Receives: Drug: aprepitant/placebo |
| placebo | Placebo comparator | 7 days treatment with study drug, order of periods (active treatment or placebo) being sorted out. Receives: Drug: aprepitant/placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Plasma aldosterone variation during orthostatic test
Measured: 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
Measured: Day 4, 5 and 7 of treatment, at each period
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Sep 2009 (estimated)
- Study startJun 2009
- Primary completionApr 2010
- Study completionJun 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Healthy VolunteersStudies of the same condition, open and under way.
- More trials run by University Hospital, RouenThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospital, Rouen
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Hervé Lefebvre, PHD, Principal investigator, University Hospital, Rouen
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00977223
- Sponsor's protocol ID
- 2007/049/HP
- Other IDs
- 2008-003367-40, 2008
- Acronym
- APHOS
- Status last verified
- Feb 2012
- First submitted
- 14 Sep 2009
- Last updated
- 16 Feb 2012
- Results posted
- No
- Data monitoring committee
- No
Publications
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.
PubMed 32471973
Study at a glance
From the registry record, last updated by the sponsor on 16 Feb 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pilot Study of the Action of the Substance P Antagonist Aprepitant on Aldosterone and Cortisol Secretion in Healthy Volunteers.
- ClinicalTrials.gov ID
- NCT00977223
- Acronym / sponsor ID
- APHOS / 2007/049/HP
- Conditions
- Healthy Volunteers
- Keywords
- Aldosterone, Substance P, Cortisol, Aprepitant, Adrenal glands
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- University Hospital, RouenUniversity, hospital or other
- Study start
- Jun 2009
- Primary completion
- Apr 2010 (actual)
- Study completion
- Jun 2010 (actual)
- First posted
- 15 Sep 2009 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Aprepitant | Experimental | Drug: aprepitant/placebo7 days treatment with study drug, order of periods (active treatment or placebo) being sorted out. |
| placebo | Placebo comparator | Drug: aprepitant/placebo7 days treatment with study drug, order of periods (active treatment or placebo) being sorted out. |
Who may qualify
- Ages
- 18 to 30 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (13 listed)
- 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;
Key exclusion criteria (13 listed)
- 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;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| aprepitant/placeboAlso: DCI : Aprepitant, Brand name : EmendAprepitant, 125 MG at day 1 then 80 MG day 2-7, once a day, per os, at 8 AM during breakfast | Drug | Aprepitant, placebo |
Primary outcome
Plasma aldosterone variation during orthostatic test
Time frame: Day 5 of treatment, at each period
1 secondary outcome
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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Feb 2012.
- Derived from this study: PubMed 32471973Wils 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Hervé Lefebvre, PHD principal investigator
University Hospital, Rouen
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study of Healthy Volunteers, run by University Hospital, Rouen at 1 site in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 13 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 16 Feb 2012. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Plasma aldosterone variation during orthostatic test (time frame: Day 5 of treatment, at each period). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00977223, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Feb 2012.