Study of the Relationships Between Refractory Hypertension, Overweight/Obesity and Sleep Apnea Syndrome (RHOOSAS)

The purpose of the study is to investigate the links between blood pressure (BP), overweight or obesity, and sleep apnea syndrome (SAS), by studying a large cohort of subjects suffering from refractory hypertension.

Primary objective

• To compare plasmatic leptin levels in patients suffering from refractory hypertension depending on whether or not they experience SAS.

Secondary objectives

• To ascertain what determines the difference in plasmatic leptin concentrations in patients suffering from refractory hypertension depending on whether or not they experience SAS.
• To characterise BP readings (from clinical and ambulatory (ABPM) measurements) in patients suffering from refractory hypertension depending on whether or not they experience SAS.
• To characterise metabolic parameters (lipids, glycaemia, adiponectin) and sympathetic nervous system effectors (adrenaline, noradrenaline and metanephrines) in patients suffering from refractory hypertension depending on whether or not they experience SAS.
• To characterise BP readings, metabolic parameters and sympathetic nervous system effectors in patients suffering from refractory hypertension according to the severity of the SAS (in those who experience this problem).
• To study, in patients with both SAS and refractory hypertension, the impact of nasal continuous positive airway pressure (CPAP) treatment on BP readings, metabolic parameters and sympathetic nervous system effectors, by comparing those who are compliant with the CPAP regimen with those who are non-compliant.

Study Overview

• Status: Completed
• Conditions: Refractory Hypertension
• Intervention / Treatment: Device: nCPAP

Detailed Description

A number of factors predispose subjects to both hypertension and SAS, including overweight/obesity and hyperinsulinism. The pathogenesis of concomitant overweight/obesity and hypertension is multifactorial. There is an independent relationship between the degree of insulin resistance and the severity of SAS. A number of studies have suggested that hormones secreted by adipose tissue are involved in the pathogenesis of both hypertension and SAS, and overweight/obesity has been shown to be associated with elevated leptin levels coupled with reduced adiponectin levels.

Leptin is produced in adipose tissue and its levels rise with overweight/obesity due to peripheral resistance to its action. A number of studies have detected high leptinemia in both hypertensives and people suffering from SAS. Leptin may activate the sympathetic nervous system and promote SAS-related hypertension.

Adiponectin which is also produced in adipose tissue has beneficial activities, notably on atherogenesis. A relationship between hypertension and adiponectin has yet to be demonstrated.

Unlike leptin, adiponectin levels do not seem to be elevated in patients with SAS.

In terms of treatment, a number of studies have shown that CPAP has a positive effect on BP readings. Although this effect is modest, it is greater in subjects with SAS and rises with the severity of this condition. The effects of CPAP on plasmatic leptin and adiponectin levels are as yet unknown.

• Study Type: Interventional
• Enrollment (Actual): 62
• Phase: Phase 3

Contacts and Locations

Study Locations

• France
  • Grenoble, France
    • University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients of either gender, of between 18 and 70
• Suffering from refractory hypertension as defined by persistent clinical hypertension (> 140/90 mm Hg according to two different readings 24 hours apart) despite at least three classes of antihypertensive drugs (including a thiazide diuretic) at appropriate doses.
• Recruited in the Cardiology Departments of the University Hospitals in Grenoble, Toulouse, Marseille and Poitiers, and in the Mozart Clinic in Paris.
• Outpatients
• Patients who have signed the consent form
• Patients affiliated to or beneficiary of the social security system

Exclusion Criteria:

• Failure to fulfil the inclusion criteria
• Treated SAS, whatever the form of the treatment
• Disease which might affect BP regulation, including Parkinson's disease, kidney or heart transplantation, dysautonomia, severe heart failure
• Atrial fibrillation or regular extrasystole (> 10/minute)
• Night- or shift-work
• Pregnant and breast-feeding women
• Patients under legal guardianship
• Incarcerated patients or adults protected by the law
• Hospitalised patients
• Ongoing participation in another clinical research study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: 1; Arm 1: Active CPAP, a nasal continuous positive airway pressure	Device: nCPAP; Active nCPAP
Sham Comparator: 2; Arm 2 : Sham CPAP :Placebo/CPAP	Device: nCPAP; Active nCPAP

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
leptinemia	inclusion visit, visit month 3, visit month 6 or 9

Secondary Outcome Measures

Outcome Measure	Time Frame
BP readings (clinical and ABPM), metabolic parameters (lipids, glycaemia, adiponectin) and sympathetic nervous system effectors (adrenaline, noradrenaline and metanephrines).	inclusion visit, visit month 3, visit month 6 or 9

Collaborators and Investigators

• Sponsor: University Hospital, Grenoble
• Collaborators: Fondation de Recherche sur l'Hypertension Artérielle
• Investigators: Principal Investigator: Jean-Philippe BAGUET, Professor, University Hospital, Grenoble

Publications and helpful links

General Publications

• Joyeux-Faure M, Baguet JP, Barone-Rochette G, Faure P, Sosner P, Mounier-Vehier C, Levy P, Tamisier R, Pepin JL. Continuous Positive Airway Pressure Reduces Night-Time Blood Pressure and Heart Rate in Patients With Obstructive Sleep Apnea and Resistant Hypertension: The RHOOSAS Randomized Controlled Trial. Front Neurol. 2018 May 8;9:318. doi: 10.3389/fneur.2018.00318. eCollection 2018.

Study record dates

Study Major Dates

• Study Start: June 1, 2008
• Primary Completion (Actual): December 1, 2013
• Study Completion (Actual): September 1, 2014

Study Registration Dates

• First Submitted: September 3, 2008
• First Submitted That Met QC Criteria: September 3, 2008
• First Posted (Estimate): September 4, 2008

Study Record Updates

• Last Update Posted (Estimate): November 7, 2014
• Last Update Submitted That Met QC Criteria: November 6, 2014
• Last Verified: November 1, 2014

More Information

Terms related to this study

• Keywords: Obesity; Obstructive sleep apnea syndrome; Refractory hypertension; Leptinemia; RHOOSAS study
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Nervous System Diseases; Respiratory Tract Diseases; Apnea; Respiration Disorders; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Overnutrition; Nutrition Disorders; Body Weight; Sleep Apnea Syndromes; Hypertension; Obesity; Overweight
• Other Study ID Numbers: 0803; 2008-A00292-53 (Registry Identifier: ID RCB)