EFFECT OF A SUBSTANCE P ANTAGONIST ON THE SECRETION OF ALDOSTERONE IN PATIENTS WITH OBSTRUCTIVE SLEEP APNEA SYNDROME AND ARTERIAL HYPERTENSION (APHOS3)

PILOT STUDY OF THE EFFECT OF A SUBSTANCE P ANTAGONIST, APREPITANT, ON THE SECRETION OF ALDOSTERONE IN PATIENTS WITH OBSTRUCTIVE SLEEP APNEA SYNDROME AND ARTERIAL HYPERTENSION

Obstructive sleep apnea syndrome (OSAS) is associated with hyperaldosteronism with elevated plasma aldosterone/renin ratio, the physiopathological mechanism of which remains uncertain. This hyperaldosteronism contributes to the development of arterial hypertension and cardiovascular complications observed in patients with OSA, in particular by increasing arterial stiffness and heart rate variability. The frequent association of OSA with obesity with metabolic syndrome suggests that excess weight could be responsible for stimulation of aldosterone secretion independent of the renin/angiotensin system. Several studies indicate in particular that the production of mineralocorticoids by the adrenals could be activated by various adipocyte secretion products such as leptin and certain fatty acids after oxidation in the liver. In addition, a recent study showed that basal aldosterone secretion is also controlled by substance P released within the adrenal tissue itself by nerve fibers belonging to the splanchnic contingent. Thus, the oral administration of aprepitant, an antagonist of the substance P receptor (NK1 receptor), to healthy volunteers induces a reduction of approximately 30% in the overall secretion of aldosterone assessed by measuring aldosteronemia and 24-hour aldosteronuria. To the extent that OSA causes sympathetic hypertonia, the hypothesis is that the associated hyperaldosteronism could result from activation of the nervous control of aldosterone secretion, involving substance P and the NK1 receptor. If this is indeed the case, the administration of aprepitant to patients with OSA should result in a significant reduction in aldosteronemia.

Study Overview

• Status: Recruiting
• Conditions: Apnea, Obstructive
• Intervention / Treatment: Drug: Aprepitant 125 and 80Mg Oral Capsule; Drug: Placebo

• Study Type: Interventional
• Enrollment (Estimated): 24
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Nell Marty; Phone Number: 02 32 88 82 65; Email: nell.marty@chu-rouen.fr
• Study Contact Backup: Name: Antoine-Guy Lopez; Phone Number: 02 32 88 90 81; Email: Antoine-Guy.Lopez@chu-rouen.fr

Study Locations

• France
  • France
    • Rouen, France, France, 76000
      • Recruiting
      • CHU de Rouen
      • Contact: Antoine-Guy Lopez; Phone Number: Antoine-Guy.Lopez@chu-rouen.fr; Email: Antoine-Guy.Lopez@chu-rouen.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Subject with severe obstructive sleep apnea syndrome (OSAS) defined by an apnea and hypopnea index (AHI) ≥ 30/h on polysomnography or ventilatory polygraphy (requiring continuous positive airway pressure).
2. Subject with essential hypertension treated medically or by lifestyle and dietary measures or newly diagnosed (defined by SBP ≥ 140 and/or DBP ≥ 90 mmHg according to current SFHTA-HAS recommendations).
3. Patient's agreement to replace diuretics with another neutral antihypertensive treatment (which does not interfere with the renin-angiotensin system), to stop consuming licorice and its derivatives, 7 to 10 days before taking the treatment. experimental and throughout the study (if applicable)

Exclusion Criteria:

1. Minor subject or subject aged over 75 years

2. Criteria relating to associated pathologies leading to particular risks:

   • Subject presenting excessive daytime sleepiness with contraindication to driving (Epworth score > 16)
   • Uncontrolled severe cardiovascular disease: myocardial infarction or stroke in the last 6 months, unstable angina, significant valvular heart disease, heart failure (≥ class II of the NYHA classification), uncontrolled cardiac arrhythmia or significant conduction abnormalities. Knowledge of chronic renal insufficiency defined by a glomerular filtration rate < 60 mL/min/1.73m2 for more than 3 months) or moderate hepatic insufficiency defined by ALT and/or AST transaminases > 3N)
   • Epilepsy
   • Known acute infections linked to HIV, HBV or HCV
   • Active cancer currently being treated
3. Contraindications to placebo and aprepitant

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo; Placebo:1 oral capsule time a day for 4 days
Experimental: Aprepitant	Drug: Aprepitant 125 and 80Mg Oral Capsule; Aprepitant 1 oral capsule time a day for 4 days (First day: 125 mg and the 3 last days: 80 mg)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of aldosterone secretion	Measurement of 24-hour aldosteronuria before and after the administration of an NK1 receptor antagonist (aprepitant) or placebo in patients suffering from obstructive sleep apnea syndrome (OSAS) and arterial hypertension	Immediately after the intervention/procedure/surgery

Collaborators and Investigators

• Sponsor: University Hospital, Rouen

Study record dates

Study Major Dates

• Study Start (Actual): March 5, 2024
• Primary Completion (Estimated): June 1, 2027
• Study Completion (Estimated): June 1, 2027

Study Registration Dates

• First Submitted: June 4, 2024
• First Submitted That Met QC Criteria: June 12, 2024
• First Posted (Actual): June 17, 2024

Study Record Updates

• Last Update Posted (Actual): May 11, 2026
• Last Update Submitted That Met QC Criteria: May 6, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Respiratory Tract Diseases; Respiration Disorders; Sleep Wake Disorders; Apnea; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Apnea Syndromes; Sleep Apnea, Obstructive; Substandard Drugs; Pharmaceutical Preparations; Counterfeit Drugs
• Other Study ID Numbers: 2020/0431/HP

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No