Evaluation of Aprepitant on Aldosterone Secretion in Patients with Obstructive Sleep Apnea and Arterial Hypertension Syndrome

The primary objective of this study is to evaluate the effect of the administration of an **NK1 receptor antagonist** (aprepitant) on aldosterone secretion in patients with obstructive sleep apnea syndrome (OSAS) and arterial hypertension. This is clinically relevant as aldosterone plays a significant role in blood pressure regulation and fluid balance, and its dysregulation is implicated in hypertension, particularly in patients with OSAS.

Secondary objectives include evaluating the effects of aprepitant on blood pressure, renin secretion, plasma and urinary electrolytes, cortisol, and ACTH levels. Additionally, the study aims to assess the treatment's tolerance in patients with obstructive sleep apnea syndrome and arterial hypertension. These secondary outcomes are important for understanding the broader physiological impacts of aprepitant and its potential therapeutic benefits or side effects in this patient population.

The clinical trial involves participants diagnosed with **obstructive sleep apnea syndrome** and arterial hypertension. The study population includes both male and female adults aged between 18 to 75 years. Participants are generally in a stable health condition, with the exception of their diagnosed conditions. The sponsor has not provided the total number of participants. Selection criteria include individuals with severe obstructive sleep apnea, defined by an apnea and hypopnea index of 30 or more per hour, and those with essential hypertension, either medically treated or newly diagnosed. Participants must agree to replace diuretics with a neutral antihypertensive treatment that does not interfere with the renin-angiotensin system. Lifestyle considerations such as diet and physical activity are not specified. The trial does not include a vulnerable population, and both genders are eligible to participate. Women of childbearing age are required to use effective mechanical contraception during the study and for two months after the last dose, with a negative urine pregnancy test at specified intervals.

The clinical trial is designed to evaluate the effect of the administration of an **NK1 receptor antagonist** (aprepitant) on **aldosterone secretion** in patients with **obstructive sleep apnea syndrome** (OSAS) and arterial hypertension. This is a randomized, double-blind, controlled trial with a therapeutic exploratory (Phase II) approach. The trial is expected to commence recruitment on March 5, 2024, and conclude by April 19, 2026. Participants will be involved in the study for a maximum treatment period of four weeks, with the trial including several key visits to monitor progress and collect data.

The sequence of study visits begins with an inclusion (screening) visit, where eligibility is confirmed based on criteria such as severe OSAS, defined by an apnea and hypopnea index (AHI) ≥ 30/h, and essential hypertension. Participants must agree to replace diuretics with another neutral antihypertensive treatment before and during the study. Following the screening, participants will undergo baseline assessments, including 24-hour aldosteronuria measurements, blood pressure, aldosteronemia, reninemia, and plasma and urinary electrolytes. These assessments will be repeated at the end of each treatment period to evaluate the primary and secondary endpoints.

Follow-up visits will occur at regular intervals to ensure adherence to the protocol and monitor any adverse events. The end-of-study visit will involve final assessments and the collection of data to determine the effect of the treatment. Participants may be withdrawn from the study if they experience significant adverse effects, fail to comply with the study protocol, or withdraw consent. The trial aims to provide valuable insights into the management of aldosterone secretion in patients with OSAS and arterial hypertension, potentially informing future therapeutic strategies.

The clinical trial involves the administration of **EMEND** 125 mg + 80 mg hard capsules, which contain the active ingredient **aprepitant**. This pharmaceutical form is a hard capsule intended for **oral use**. The dosage regimen includes a maximum daily dose of 125 mg, with a total maximum dose of 365 mg over a treatment period of up to 4 days. The primary objective of the trial is to evaluate the effect of aprepitant, an NK1 receptor antagonist, on aldosterone secretion in patients diagnosed with obstructive sleep apnea syndrome and arterial hypertension. The administration schedule and participant compliance are monitored to ensure adherence to the prescribed dosing regimen.

In addition to the experimental treatment, the trial utilizes **lactose monohydrate** as a placebo. Lactose monohydrate is provided in tablet form and is also administered orally. The placebo is used to maintain the blinding of the study and to serve as a comparator to the active treatment. The dosing schedule for the placebo mirrors that of the active treatment, with a maximum daily dose of 125 mg and a total maximum dose of 365 mg over the same 4-day treatment period. Compliance with the placebo administration is similarly monitored to ensure the integrity of the trial results.

Efficacy in this clinical trial will be assessed through both primary and secondary endpoints. The primary endpoint involves the measurement of **24-hour aldosteronuria**, which will be evaluated at the beginning and end of each treatment period. This parameter is crucial for determining the effect of the NK1 receptor antagonist, aprepitant, on aldosterone secretion in patients with obstructive sleep apnea syndrome and arterial hypertension.

Secondary endpoints include a comprehensive set of measurements: blood pressure, aldosteronemia, reninemia, plasma and urinary electrolytes, 24-hour plasma and urinary cortisol, and plasma ACTH. These will also be assessed at the beginning and end of each treatment period. The collection and analysis of these parameters will provide additional insights into the physiological effects of the treatment. The trial is designed to ensure that these measurements are systematically collected and analyzed to evaluate the therapeutic impact of the intervention accurately.