Fludrocortisone in Healthy Volunteers (AFLUCO4)

Healthy Volunteers Clinical Trial

— AFLUCO4  

Official title:

Hemodynamic and Biological Effects of 3 Increasing Doses of Fludrocortisone in Healthy Volunteers

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02140918
• Other study ID #: 2013-004794-27
• Status: Completed
• Phase: Phase 2
• Start date: July 1, 2014
• Est. completion date: April 20, 2016

Study information

• Verified date: August 2018
• Source: Rennes University Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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.

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 16
• Est. completion date: April 20, 2016
• Est. primary completion date: April 20, 2016
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 20 Years to 25 Years

Eligibility

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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

Related Conditions & MeSH terms

• Healthy Volunteers

Intervention

Drug:
• Fludrocortisone 100 µg
Fludrocortisone 100 µg/day
• Fludrocortisone 200 µg
Fludrocortisone 200 µg/day
• Fludrocortisone 400 µg
Fludrocortisone 400 µg/day
• Placebo

Locations

Country	Name	City	State
France	Rennes University Hospital	Rennes

Sponsors (1)

Lead Sponsor	Collaborator
Rennes University Hospital

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Phenylephrine mean blood pressor dose-response relationship.		1.5 hour after fludrocortisone administration
Secondary	Cardiac systolic and diastolic function assessed par transthoracic echocardiography during phenylephrine administration		between 1.5 and 2.5 hours after fludrocortisone administration
Secondary	Systemic hemodynamic parameters	Systolic, diastolic and mean arterial pressures, heart rate, peripheral pulse pressure, cardiac output, stroke volume, systemic vascular resistances	30min before and 1h, 2h, 3h, 4h, 5h, 6h after fludrocortisone administration
Secondary	Arterial stiffness : carotid-femoral pulse wave velocity		30min before and 1h, 2h, 3h, 4h, 5h, 6h after fludrocortisone administration
Secondary	Central aortic hemodynamic parameters	Aortic systolic, diastolic and mean arterial pressures, central pulse pressure, central pressure augmentation index (AIx)	30min before and 1h, 2h, 3h, 4h, 5h, 6h after fludrocortisone administration
Secondary	Plasma parameters	Blood electrolytes, urea, creatinine, glucose, renin, aldosterone	30min before and 1h, 2h, 3h, 4h, 5h, 6h after fludrocortisone administration
Secondary	Urinary parameters	Diuresis, urinary electrolytes, urea, creatinine, glucose	30min before and 2h, 4h, 6h after fludrocortisone administration
Secondary	Area under the plasma concentration versus time curve (AUC)		Just before and 5min, 10min, 20min, 30min, 1h, 1h30, 2h, 3h, 4h, 5h, 6h after fludrocortisone administration
Secondary	Plasma half-life of fludrocortisone		Just before and 5min, 10min, 20min, 30min, 1h, 1h30, 2h, 3h, 4h, 5h, 6h after fludrocortisone administration
Secondary	Total Body Clearance		Just before and 5min, 10min, 20min, 30min, 1h, 1h30, 2h, 3h, 4h, 5h, 6h after fludrocortisone administration
Secondary	Apparent volume of distribution		Just before and 5min, 10min, 20min, 30min, 1h, 1h30, 2h, 3h, 4h, 5h, 6h after fludrocortisone administration