Effects of Fludrocortisone and Hydrocortisone in Healthy Volunteers With Aldosterone Induced Suppression

Study Overview
=================
Brief Summary
-----------------
Septic shock (associated with relative adrenal insufficiency) is characterized by decreased arterial responsiveness to catecholamines. The association of hydrocortisone and fludrocortisone has demonstrated an improvement in survival in septic shock patients. If hydrocortisone has shown to increase vascular responsiveness, the role of fludrocortisone remains to be elucidated. The purpose of our study is to investigate the effect of a physiological dose of fludrocortisone and/or hydrocortisone on phenylephrine-mean arterial pressure dose-response relationship in healthy volunteers with aldosterone suppression induced by intravenous sodium loading.

Official Title
-----------------
Hemodynamic and Biological Effects of Fludrocortisone and Hydrocortisone, in Healthy Volunteers With Aldosterone Induced Suppression

Conditions
-----------------
Renin Angiotensin

Intervention / Treatment
-----------------
* Drug: Fludrocortisone
* Drug: Hydrocortisone
* Drug: Placebo of Fludrocortisone
* Drug: Placebo of Hydrocortisone


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Men between 20 and 30 years Body Mass Index between 18 kg/m² and 25 kg/m² Normal clinical examination Normal biological variables Normal electrocardiogram and echocardiography Written, voluntary informed consent Non smoker since at least a year Non-inclusion Criteria: Any history of significant allergy Subjects with abnormal renal, pulmonary, cardiovascular, endocrine or hepatic function Medication during the study Alcohol consumption more than 30g/day or drug addiction Positive serology for hepatitis B virus (HBV), hepatitis C virus (HCV) or HIV. Exclusion period mentioned on the Healthy Volunteers National list Persons deprived of freedom or under guardianship

Ages Eligible for Study
-----------------
Minimum Age: 20 Years
Maximum Age: 30 Years

Sexes Eligible for Study
-----------------
Male

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>Fludrocortisone and Hydrocortisone | Drug: Fludrocortisone<br>* 50 µg of fludrocortisone per os<br>Drug: Hydrocortisone<br>* 50 mg of intravenous hydrocortisone<br>|
| Experimental: 2<br>Fludrocortisone and placebo of Hydrocortisone | Drug: Fludrocortisone<br>* 50 µg of fludrocortisone per os<br>Drug: Placebo of Hydrocortisone<br>* 2 ml of isotonic saline solution<br>|
| Experimental: 3<br>Placebo of Fludrocortisone and Hydrocortisone | Drug: Hydrocortisone<br>* 50 mg of intravenous hydrocortisone<br>Drug: Placebo of Fludrocortisone<br>* Tablet of placebo of Fludrocortisone<br>|
| Placebo Comparator: 4<br>Placebo of Fludrocortisone and placebo of Hydrocortisone | Drug: Placebo of Fludrocortisone<br>* Tablet of placebo of Fludrocortisone<br>Drug: Placebo of Hydrocortisone<br>* 2 ml of isotonic saline solution<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Phenylephrine-mean arterial pressure dose-response relationship |  | Between 1.5 and 3 hours after treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Systolic and diastolic arterial pressures, heart rate, cardiac output, systemic vascular resistances |  | Between administration time and 24 hours after treatment | 
| Central aortic pressures, Augmentation Index (Aix) |  | Between administration time and 12 hours after treatment | 
| Arterial stiffness: Carotid-femoral Pulse Wave Velocity |  | Between administration time and 12 hours after treatment | 
| Humeral diameter and distensibility |  | Between administration time and 12 hours after treatment | 
| Plasma electrolytes, blood glucose, serum creatinine |  | Between administration time and 24 hours after treatment | 
| Plasma renin, aldosterone, norepinephrine, epinephrine, hydrocortisone, fludrocortisone concentrations |  | Between administration time and 24 hours after treatment | 
| Urinary electrolytes excretion |  | Between administration time and 24 hours after treatment |