Fludrocortisone in Healthy Volunteers (AFLUCO4)

NCT ID: NCT02140918

Last Updated: 2018-08-29

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 16 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-07-01
• Study Completion Date: 2016-04-20

Brief 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.

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: QUADRUPLE

Study Groups

Fludrocortisone 100 μg

• 100 μg/day (25 µg four times daily) of fludrocortisone during 5 days
• Investigations the sixth day

Group Type: EXPERIMENTAL

Fludrocortisone 100 μg

Intervention Type: DRUG

Fludrocortisone 100 μg/day

Fludrocortisone 200 μg

• 200 μg/day (50 µg four times daily) of fludrocortisone during 5 days
• Investigations the sixth day

Group Type: EXPERIMENTAL

Fludrocortisone 200 μg

Intervention Type: DRUG

Fludrocortisone 200 μg/day

Fludrocortisone 400 μg

• 400 μg/day (100 µg four times daily) of fludrocortisone during 5 days
• Investigations the sixth day

Group Type: EXPERIMENTAL

Fludrocortisone 400 μg

Intervention Type: DRUG

Fludrocortisone 400 μg/day

Placebo

• Placebo (four times daily) during 5 days
• Investigations the sixth day

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Interventions

Fludrocortisone 100 μg

Fludrocortisone 100 μg/day

Intervention Type: DRUG

Fludrocortisone 200 μg

Fludrocortisone 200 μg/day

Intervention Type: DRUG

Fludrocortisone 400 μg

Fludrocortisone 400 μg/day

Intervention Type: DRUG

Placebo

Intervention Type: DRUG

Eligibility Criteria

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

• Minimum Eligible Age: 20 Years
• Maximum Eligible Age: 25 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: Yes

Sponsors

Rennes University Hospital

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Bruno Laviolle, MD

Role: PRINCIPAL_INVESTIGATOR

Centre d'Investigation Clinique Inserm 1414, Service de Pharmacologie Clinique, Hôpital de Pontchaillou

Eric Bellissant, MD, PHD

Role: STUDY_CHAIR

Centre d'Investigation Clinique Inserm 1414, Service de Pharmacologie Clinique, Hôpital de Pontchaillou

Locations

Rennes University Hospital

Rennes, , France

Countries

France

Other Identifiers

2013-004794-27

Identifier Type: -

Identifier Source: org_study_id