Healthy VolunteersPhase 2AFLUCO4NCT02140918
Fludrocortisone in Healthy Volunteers (AFLUCO4)
A Phase 2 study testing Fludrocortisone 100 μg, Fludrocortisone 200 μg and Fludrocortisone 400 μg in people with Healthy Volunteers, run by Rennes University Hospital at 1 site in France.
Trial summary
Fludrocortisone, in association with hydrocortisone, has demonstrated an improvement in survival in septic shock patients with relative adrenal insufficiency. However, the utility of low doses of steroids and in particular of mineralocorticoids in septic shock is still discussed. Read more about this study
- Who is it for?
- Ages 20 to 25 years, men onlyHealthy volunteers can take part
- Conditions the study is for
- Healthy Volunteers
- What is being tested?
- Fludrocortisone 100 μg, Fludrocortisone 200 μg and Fludrocortisone 400 μg
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 16 participants
- Where
- 1 siteFrance
- Study dates
- 1 Jul 2014to 20 Apr 2016
- Phase
- Phase 2
- 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 20 to 25 years
- Men only
- Healthy volunteers accepted
- Adult
Who may be able to join
- Men aged 20 to 25 years
- Body Mass Index between 20 kg/m² and 25 kg/m²
- Nonsmoker since at least 6 months
- Normal clinical examination, electrocardiogram and transthoracic echocardiography
- Normal routine biological parameters
- Written informed consent
Who cannot join
- History of significant allergy
- Resting heart rate < 50 bpm
- Subjects with abnormal hepatic or renal function, or cardiovascular, pulmonary, endocrine or psychiatric disease
- Ongoing medication during the study
- Alcohol consumption more than 30g/day or drug addiction
- Exclusion period mentioned on the national registry for clinical trials volunteers.
- Subject under legal protection
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Hemodynamic and Biological Effects of 3 Increasing Doses of Fludrocortisone in Healthy Volunteers
Fludrocortisone, in association with hydrocortisone, has demonstrated an improvement in survival in septic shock patients with relative adrenal insufficiency. However, the utility of low doses of steroids and in particular of mineralocorticoids in septic shock is still discussed.
The purpose of the investigators study is to investigate the effects of 3 increasing doses of fludrocortisone (100 μg, 200 μg, 400 μg) in order to determine which dose allows the best pressor response to phenylephrine in healthy volunteers, and simultaneously assess their respective hemodynamic and biological effects.
Read the detailed description
In a previous study (AFLUCO2) in healthy volunteers with saline-induced hypoaldosteronism, the investigators found that single doses of both hydrocortisone and fludrocortisone induced a significant decrease in the pressor response to phenylephrine, probably due to a rapid non-genomic vasodilatory mechanism, and that these effects were additive.
The investigators also showed that, at the doses used in septic shock, hydrocortisone induced more pronounced mineralocorticoid effects than fludrocortisone and also induced systemic hemodynamic effects whereas fludrocortisone did not.
The investigators now want to perform a dose-response study under normal conditions (ie without saline-induced hypoaldosteronism) and after repeated administrations, to determine the optimal dose of fludrocortisone that allows an increase in the pressor response to phenylephrine and to characterize its concomitant hemodynamic and biological effects.
This placebo-controlled, randomized, double-blind, cross-over, 4-periods (fludrocortisone 100 μg/day, 200 μg/day, 400 μg/day, or placebo) study aims to investigate hemodynamic and biological effects of fludrocortisone administered orally during 5 days, in healthy volunteers.
Each period will be separated from the next one by a washout interval of at least 14 days.
- Conditions
- Healthy Volunteers
- Being tested
- Fludrocortisone 100 μg, Fludrocortisone 200 μg, Fludrocortisone 400 μg, Placebo
- Keywords
- Fludrocortisone, Mineralocorticoids, Hemodynamics, Pharmacokinetics
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Fludrocortisone 100 μgDrug
Fludrocortisone 100 μg/day
Fludrocortisone 200 μgDrug
Fludrocortisone 200 μg/day
Fludrocortisone 400 μgDrug
Fludrocortisone 400 μg/day
PlaceboDrug
| Study group | Role | What they receive |
|---|---|---|
| Fludrocortisone 100 μg | Experimental | * 100 μg/day (25 µg four times daily) of fludrocortisone during 5 days
* Investigations the sixth day Receives: Drug: Fludrocortisone 100 μg |
| Fludrocortisone 200 μg | Experimental | * 200 μg/day (50 µg four times daily) of fludrocortisone during 5 days
* Investigations the sixth day Receives: Drug: Fludrocortisone 200 μg |
| Fludrocortisone 400 μg | Experimental | * 400 μg/day (100 µg four times daily) of fludrocortisone during 5 days
* Investigations the sixth day Receives: Drug: Fludrocortisone 400 μg |
| Placebo | Placebo comparator | * Placebo (four times daily) during 5 days
* Investigations the sixth day Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Phenylephrine mean blood pressor dose-response relationship.
Measured: 1.5 hour after fludrocortisone administration
Secondary outcomes (10)
Cardiac systolic and diastolic function assessed par transthoracic echocardiography during phenylephrine administration
Measured: between 1.5 and 2.5 hours after fludrocortisone administration
Systemic hemodynamic parameters
Systolic, diastolic and mean arterial pressures, heart rate, peripheral pulse pressure, cardiac output, stroke volume, systemic vascular resistances
Measured: 30min before and 1h, 2h, 3h, 4h, 5h, 6h after fludrocortisone administration
Arterial stiffness : carotid-femoral pulse wave velocity
Measured: 30min before and 1h, 2h, 3h, 4h, 5h, 6h after fludrocortisone administration
Central aortic hemodynamic parameters
Aortic systolic, diastolic and mean arterial pressures, central pulse pressure, central pressure augmentation index (AIx)
Measured: 30min before and 1h, 2h, 3h, 4h, 5h, 6h after fludrocortisone administration
Plasma parameters
Blood electrolytes, urea, creatinine, glucose, renin, aldosterone
Measured: 30min before and 1h, 2h, 3h, 4h, 5h, 6h after fludrocortisone administration
Urinary parameters
Diuresis, urinary electrolytes, urea, creatinine, glucose
Measured: 30min before and 2h, 4h, 6h after fludrocortisone administration
Area under the plasma concentration versus time curve (AUC)
Measured: Just before and 5min, 10min, 20min, 30min, 1h, 1h30, 2h, 3h, 4h, 5h, 6h after fludrocortisone administration
Plasma half-life of fludrocortisone
Measured: Just before and 5min, 10min, 20min, 30min, 1h, 1h30, 2h, 3h, 4h, 5h, 6h after fludrocortisone administration
Total Body Clearance
Measured: Just before and 5min, 10min, 20min, 30min, 1h, 1h30, 2h, 3h, 4h, 5h, 6h after fludrocortisone administration
Apparent volume of distribution
Measured: Just before and 5min, 10min, 20min, 30min, 1h, 1h30, 2h, 3h, 4h, 5h, 6h after fludrocortisone administration
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 May 2014 (estimated)
- Study start1 Jul 2014
- Primary completion20 Apr 2016
- Study completion20 Apr 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Healthy VolunteersStudies of the same condition, open and under way.
- More trials run by Rennes University HospitalThe 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 2
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 16 participants (actual)
Sponsor and investigators
- Lead sponsor
- Rennes University Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Bruno Laviolle, MD, Principal investigator, Centre d'Investigation Clinique Inserm 1414, Service de Pharmacologie Clinique, Hôpital de PontchaillouEric Bellissant, MD, PHD, Study chair, Centre d'Investigation Clinique Inserm 1414, Service de Pharmacologie Clinique, Hôpital de Pontchaillou
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02140918
- Sponsor's protocol ID
- 2013-004794-27
- Acronym
- AFLUCO4
- Status last verified
- Aug 2018
- First submitted
- 12 May 2014
- Last updated
- 29 Aug 2018
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 29 Aug 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Hemodynamic and Biological Effects of 3 Increasing Doses of Fludrocortisone in Healthy Volunteers
- ClinicalTrials.gov ID
- NCT02140918
- Acronym / sponsor ID
- AFLUCO4 / 2013-004794-27
- Conditions
- Healthy Volunteers
- Keywords
- Fludrocortisone, Mineralocorticoids, Hemodynamics, Pharmacokinetics
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 16 participants (actual)
- Lead sponsor
- Rennes University HospitalUniversity, hospital or other
- Study start
- 1 Jul 2014 (actual)
- Primary completion
- 20 Apr 2016 (actual)
- Study completion
- 20 Apr 2016 (actual)
- First posted
- 16 May 2014 (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.
Fludrocortisone, in association with hydrocortisone, has demonstrated an improvement in survival in septic shock patients with relative adrenal insufficiency. However, the utility of low doses of steroids and in particular of mineralocorticoids in septic shock is still discussed.
The purpose of the investigators study is to investigate the effects of 3 increasing doses of fludrocortisone (100 μg, 200 μg, 400 μg) in order to determine which dose allows the best pressor response to phenylephrine in healthy volunteers, and simultaneously assess their respective hemodynamic and biological effects.
Detailed description
In a previous study (AFLUCO2) in healthy volunteers with saline-induced hypoaldosteronism, the investigators found that single doses of both hydrocortisone and fludrocortisone induced a significant decrease in the pressor response to phenylephrine, probably due to a rapid non-genomic vasodilatory mechanism, and that these effects were additive.
The investigators also showed that, at the doses used in septic shock, hydrocortisone induced more pronounced mineralocorticoid effects than fludrocortisone and also induced systemic hemodynamic effects whereas fludrocortisone did not.
The investigators now want to perform a dose-response study under normal conditions (ie without saline-induced hypoaldosteronism) and after repeated administrations, to determine the optimal dose of fludrocortisone that allows an increase in the pressor response to phenylephrine and to characterize its concomitant hemodynamic and biological effects.
This placebo-controlled, randomized, double-blind, cross-over, 4-periods (fludrocortisone 100 μg/day, 200 μg/day, 400 μg/day, or placebo) study aims to investigate hemodynamic and biological effects of fludrocortisone administered orally during 5 days, in healthy volunteers.
Each period will be separated from the next one by a washout interval of at least 14 days.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Fludrocortisone 100 μg | Experimental | Drug: Fludrocortisone 100 μg* 100 μg/day (25 µg four times daily) of fludrocortisone during 5 days * Investigations the sixth day |
| Fludrocortisone 200 μg | Experimental | Drug: Fludrocortisone 200 μg* 200 μg/day (50 µg four times daily) of fludrocortisone during 5 days * Investigations the sixth day |
| Fludrocortisone 400 μg | Experimental | Drug: Fludrocortisone 400 μg* 400 μg/day (100 µg four times daily) of fludrocortisone during 5 days * Investigations the sixth day |
| Placebo | Placebo comparator | Drug: Placebo* Placebo (four times daily) during 5 days * Investigations the sixth day |
Who may qualify
- Ages
- 20 to 25 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (6 listed)
- Men aged 20 to 25 years
- Body Mass Index between 20 kg/m² and 25 kg/m²
- Nonsmoker since at least 6 months
- Normal clinical examination, electrocardiogram and transthoracic echocardiography
- Normal routine biological parameters
Key exclusion criteria (7 listed)
- History of significant allergy
- Resting heart rate < 50 bpm
- Subjects with abnormal hepatic or renal function, or cardiovascular, pulmonary, endocrine or psychiatric disease
- Ongoing medication during the study
- Alcohol consumption more than 30g/day or drug addiction
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 |
|---|---|---|
| Fludrocortisone 100 μgFludrocortisone 100 μg/day | Drug | Fludrocortisone 100 μg |
| Fludrocortisone 200 μgFludrocortisone 200 μg/day | Drug | Fludrocortisone 200 μg |
| Fludrocortisone 400 μgFludrocortisone 400 μg/day | Drug | Fludrocortisone 400 μg |
| Placebo | Drug | Placebo |
Primary outcome
Phenylephrine mean blood pressor dose-response relationship.
Time frame: 1.5 hour after fludrocortisone administration
10 secondary outcomes
Cardiac systolic and diastolic function assessed par transthoracic echocardiography during phenylephrine administration
Time frame: between 1.5 and 2.5 hours after fludrocortisone administration
Systemic hemodynamic parameters
Time frame: 30min before and 1h, 2h, 3h, 4h, 5h, 6h after fludrocortisone administration
Arterial stiffness : carotid-femoral pulse wave velocity
Time frame: 30min before and 1h, 2h, 3h, 4h, 5h, 6h after fludrocortisone administration
Central aortic hemodynamic parameters
Time frame: 30min before and 1h, 2h, 3h, 4h, 5h, 6h after fludrocortisone administration
Plasma parameters
Time frame: 30min before and 1h, 2h, 3h, 4h, 5h, 6h after fludrocortisone administration
Urinary parameters
Time frame: 30min before and 2h, 4h, 6h after fludrocortisone administration
Area under the plasma concentration versus time curve (AUC)
Time frame: Just before and 5min, 10min, 20min, 30min, 1h, 1h30, 2h, 3h, 4h, 5h, 6h after fludrocortisone administration
Plasma half-life of fludrocortisone
Time frame: Just before and 5min, 10min, 20min, 30min, 1h, 1h30, 2h, 3h, 4h, 5h, 6h after fludrocortisone administration
Total Body Clearance
Time frame: Just before and 5min, 10min, 20min, 30min, 1h, 1h30, 2h, 3h, 4h, 5h, 6h after fludrocortisone administration
Apparent volume of distribution
Time frame: Just before and 5min, 10min, 20min, 30min, 1h, 1h30, 2h, 3h, 4h, 5h, 6h after fludrocortisone administration
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 29 Aug 2018.
Related trials for Healthy Volunteers
Not yet recruiting
Neuroergonomic Analysis of a Brain-Computer Interface Device (BCI)
Healthy Volunteers - Male and Female
RecruitingPhase 1
First-in-Human Trial to Assess REGN20423 in Healthy Adult Participants and Adult Participants With Atopic Dermatitis
Healthy Volunteer, Atopic Dermatitis
Not yet recruitingObservational study
Establishment of Biobank of Nasal Epithelium Samples From Healthy Volunteers
Healthy
RecruitingObservational study
Improved Methods of Cell Selection for Bone Marrow Transplant Alternatives
Graft-Versus-Host Disease, Graft-versus-leukemia
Not yet recruitingObservational study
Screening Protocol
Pain
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.
Bruno Laviolle, MD principal investigator
Centre d'Investigation Clinique Inserm 1414, Service de Pharmacologie Clinique, Hôpital de Pontchaillou
Eric Bellissant, MD, PHD study chair
Centre d'Investigation Clinique Inserm 1414, Service de Pharmacologie Clinique, Hôpital de Pontchaillou
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Fludrocortisone 100 μg, Fludrocortisone 200 μg and Fludrocortisone 400 μg in people with Healthy Volunteers, run by Rennes University Hospital 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 6 inclusion and 7 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 29 Aug 2018. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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?
Phenylephrine mean blood pressor dose-response relationship. (time frame: 1.5 hour after fludrocortisone administration). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 29 Aug 2018.