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NCT Number: NCT02140918

Fludrocortisone in Healthy Volunteers (AFLUCO4)

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.

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Key information

Conditions

Healthy Volunteers

Age range

20 year–25 year

Sex eligibility

Male

Study type

Interventional

Phase

Phase 2

Primary location

Rennes University Hospital

Rennes, 35033, France

About this study

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.

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Fludrocortisone 100 μg

Drug

Fludrocortisone 100 μg/day

Fludrocortisone 200 μg

Drug

Fludrocortisone 200 μg/day

Fludrocortisone 400 μg

Drug

Fludrocortisone 400 μg/day

Placebo

Drug

Primary outcomes

  1. Phenylephrine mean blood pressor dose-response relationship.

    Time frame: 1.5 hour after fludrocortisone administration

Secondary outcomes

  1. Cardiac systolic and diastolic function assessed par transthoracic echocardiography during phenylephrine administration

    Time frame: between 1.5 and 2.5 hours after fludrocortisone administration

  2. Systemic hemodynamic parameters

    Time frame: 30min before and 1h, 2h, 3h, 4h, 5h, 6h after fludrocortisone administration

    Systolic, diastolic and mean arterial pressures, heart rate, peripheral pulse pressure, cardiac output, stroke volume, systemic vascular resistances

  3. Arterial stiffness : carotid-femoral pulse wave velocity

    Time frame: 30min before and 1h, 2h, 3h, 4h, 5h, 6h after fludrocortisone administration

  4. Central aortic hemodynamic parameters

    Time frame: 30min before and 1h, 2h, 3h, 4h, 5h, 6h after fludrocortisone administration

    Aortic systolic, diastolic and mean arterial pressures, central pulse pressure, central pressure augmentation index (AIx)

  5. Plasma parameters

    Time frame: 30min before and 1h, 2h, 3h, 4h, 5h, 6h after fludrocortisone administration

    Blood electrolytes, urea, creatinine, glucose, renin, aldosterone

  6. Urinary parameters

    Time frame: 30min before and 2h, 4h, 6h after fludrocortisone administration

    Diuresis, urinary electrolytes, urea, creatinine, glucose

  7. 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

  8. Plasma half-life of fludrocortisone

    Time frame: Just before and 5min, 10min, 20min, 30min, 1h, 1h30, 2h, 3h, 4h, 5h, 6h after fludrocortisone administration

  9. Total Body Clearance

    Time frame: Just before and 5min, 10min, 20min, 30min, 1h, 1h30, 2h, 3h, 4h, 5h, 6h after fludrocortisone administration

  10. Apparent volume of distribution

    Time frame: Just before and 5min, 10min, 20min, 30min, 1h, 1h30, 2h, 3h, 4h, 5h, 6h after fludrocortisone administration

Sponsors and collaborators

Lead sponsor

Rennes University Hospital

Other

Registry information

Official study title

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

Acronym: AFLUCO4

Important dates

Study start
2014
Primary completion
2016
Study completion
2016
First posted
May 16, 2014
Registry last updated
Aug 29, 2018

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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