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

Condition(s) targeted: Renin Angiotensin

Intervention: Fludrocortisone (Drug); Hydrocortisone (Drug); Placebo of Fludrocortisone (Drug); Placebo of Hydrocortisone (Drug)

Phase: Phase 1/Phase 2

Status: Terminated

Sponsored by: Rennes University Hospital

Official(s) and/or principal investigator(s):
Bruno LAVIOLLE, MD, Principal Investigator, Affiliation: Rennes University Hospital
Eric BELLISSANT, MD, PhD, Study Chair, Affiliation: Rennes University Hospital

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

Study design: Allocation: Randomized, Endpoint Classification: Pharmacokinetics/Dynamics Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Basic Science

Primary outcome: Phenylephrine-mean arterial pressure dose-response relationship

Secondary outcome:

Systolic and diastolic arterial pressures, heart rate, cardiac output, systemic vascular resistances

Central aortic pressures, Augmentation Index (Aix)

Arterial stiffness: Carotid-femoral Pulse Wave Velocity

Humeral diameter and distensibility

Plasma electrolytes, blood glucose, serum creatinine

Plasma renin, aldosterone, norepinephrine, epinephrine, hydrocortisone, fludrocortisone concentrations

Urinary electrolytes excretion

Minimum age: 20 Years. Maximum age: 30 Years. Gender(s): Male.

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

Unité d'Investigation Clinique - Hôpital de Pontchaillou, Rennes 35033, France

Starting date: May 2008
Last updated: March 1, 2012