Fludrocortisone's Test in Salt Sensitivity

Fludrocortisone's Test in the Identification of Salt Sensitivity

The main hypothesis of this study is look for a clinical and fast test to identify salt sensitivity by administration of fludrocortisone.

Study Overview

• Status: Unknown
• Conditions: Hypertension
• Intervention / Treatment: Other: Diet cycles; Drug: Fludrocortisone

Detailed Description

The relationship between excessive salt intake and hypertension is well established in the literature. However, the intensity of blood pressure increase in response to such intake varies among individuals. The salt sensitivity is, therefore, measurement of blood pressure response to the variation of salt content in the diet in each individual. The importance of sensitivity to salt has been well demonstrated, with higher mortality in both hypertensive patients and in normotensives subjects. Despite this importance, the methods of assessment salt sensitivity are difficult to be adopted into clinical practice. The test considered the standard for sensitivity to salt is the administration of two cycles of low and high sodium diets, and checked the change in mean arterial pressure between the end of the first and second cycles. Note, therefore, that the supply of diets, as well as patient compliance, are difficult in routine clinical practice. The aim of this study is to compare the administration of fludrocortisone in identifying patients with salt sensitive with the gold standard low and high sodium diets. A experimental cross-over study, with 40 uncomplicated hypertensive patients, will be conducted. Initially, all patients are going to stay in a period of washout of antihypertensive medications with a duration of four weeks, receiving placebo. Following this, they will be submitted for salt sensitivity in two phases: during the cycle of diets, lasting two weeks, and during administration of fludrocortisone in a dose of 0.4 mg/day for 7 days. Between these two phases will be a period of four weeks. The order of the phases will be divided by simple randomization. Moreover, we will evaluate the relationship between blood pressure and 24-hour urinary sodium excretion during cycles of diet low / high sodium. After the study, the test accuracy of fludrocortisone will be analyzed by calculating the sensitivity, specificity and positive predictive value and negative, in addition to the construction of a ROC curve for determining a cutoff point to improve the specificity and sensitivity of the test.

• Study Type: Interventional
• Enrollment (Anticipated): 40
• Phase: Phase 4

Contacts and Locations

Study Locations

• Brazil
  • SP
    • Sao Paulo, SP, Brazil, 05403-000
      • Recruiting
      • General Hospital of School of Medicine - Universiy of Sao Paulo
      • Contact: Andrea P Abreu, MD; Phone Number: (5511) 86921219; Email: andreapioabreu@gmail.com
      • Contact: Decio Mion Junior, MD, PhD; Phone Number: (5511) 26617686; Email: deciomion@uol.com.br
      • Sub-Investigator: Andrea P Abreu, MD
      • Principal Investigator: Decio Mion Junior, MD, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age 40 to 65 years
• Both sexes and all ethnicities;
• Body Mass Index (BMI) between 20 and 30 kg/m2;
• Patients with hypertension with systolic blood pressure (SBP) between 140 and 159 mmHg and diastolic blood pressure (DBP) between 90 mm Hg and 99 mm Hg, without medication or after four weeks of placebo

Exclusion Criteria:

• Moderate/severe hypertension (BP ≥ 160/100 mm Hg) or secondary cause of hypertension;
• Use of more than two antihypertensive classes at the time of selection;
• Presence of diabetes mellitus or other endocrine disorders;
• Presence of renal impairment (creatinine clearance <60 ml / min, calculated by Cockcroft-Gault formula);
• Presence of heart failure;
• Presence of cardiac arrhythmias;
• History of stroke, coronary heart disease (myocardial infarction, angina) and peripheral vascular insufficiency;
• Presence of liver failure;
• Alcoholism;
• Psychiatric disorders;
• Use of anovulatory or continuous use of other drugs, such as hormonal or nonhormonal anti-inflammatory drugs that may interfere with blood pressure.
• Pregnant women

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Diet cycles; The patient will be analysed for salt sensitivity by two cycle of diets: low salt diet(40mEq Sodium/day by 7 days) and high salt diet (240mEq Sodium/day by 7 days). After 4 weeks without any intervention, the patient will received fludrocortisone in a dose of 0.4 mg/day for 7 days.	Other: Diet cycles; Two cycle of diets: low salt diet(40mEq Sodium/day by 7 days) and high salt diet (240mEq Sodium/day by 7 days)
Other: Fludrocortisone; The patient will received fludrocortisone in a dose of 0.4 mg/day for 7 days. After 4 weeks without any intervention, the patient will be analysed for salt sensitivity by two cycle of diets: low salt diet(40mEq Sodium/day by 7 days) and high salt diet (240mEq Sodium/day by 7 days).	Drug: Fludrocortisone; Fludrocortisone in a dose of 0.4 mg/day for 7 days

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Blood pressure difference	Patient will be analised for salt sensitivity in two phases: during the cycle of diets (low and high salt), lasting two weeks, and during administration of fludrocortisone (0.4 mg/day for 7 days). In the begin and finish of each phase (diets and fludrocortisone), blood pressure will be measure by oscilometric methods in the office and by ambulatory blood pressure monitoring (ABPM) and home blood pressure monitoring (HBPM) out-of-office. The difference of blood pressure between each phase will be used to classify the patient in salt sensitive or salt resistant.	Baseline and 11 weeks

Collaborators and Investigators

• Sponsor: Fundação de Amparo à Pesquisa do Estado de São Paulo
• Investigators: Principal Investigator: Decio Mion Junior, MD, PhD, General Hospital of School of Medicine - Universiy of Sao Paulo

Publications and helpful links

General Publications

• Pio-Abreu A, de Castro I, da Silva GV, Ortega KC, Mion D Jr. Oral Fludrocortisone Test for Salt-Sensitive Screening in Hypertensive Patients: A Randomized Crossover Trial. Int J Hypertens. 2018 Nov 15;2018:7437858. doi: 10.1155/2018/7437858. eCollection 2018.

Study record dates

Study Major Dates

• Study Start: July 1, 2011
• Primary Completion (Anticipated): September 1, 2012
• Study Completion (Anticipated): June 1, 2013

Study Registration Dates

• First Submitted: October 14, 2011
• First Submitted That Met QC Criteria: October 14, 2011
• First Posted (Estimate): October 18, 2011

Study Record Updates

• Last Update Posted (Estimate): October 21, 2011
• Last Update Submitted That Met QC Criteria: October 20, 2011
• Last Verified: October 1, 2011

More Information

Terms related to this study

• Keywords: hypertension; fludrocortisone; salt sensitivity
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Immune System Diseases; Hypersensitivity; Hypertension; Anti-Inflammatory Agents; Fludrocortisone
• Other Study ID Numbers: FAPESP 2010/170726