Nasal Tramazoline and Dexamethazone in Obstructive Sleep Apnea (OSA) Patients Tramazoline and
Condition: Obstructive Sleep Apnea Syndrome
MeSH terms: Apnea; Sleep Apnea Syndromes; Sleep Apnea, Obstructive
Study type: Interventional

Summary: 
      Nasal resistance presents considerable variations during night[8]. Additionally, Oral and
      oro-nasal breathing epochs exhibit strong correlation with the number of apnoea/hypopnoeas
      [7].The hypothesis that the present study aims to test is whether the pharmacological
      prevention of increased nasal resistance during night could alter breathing route pattern and
      lead to a decrease in the number of apnoea/hypopnoeas in OSA patients with normal nasal
      resistance.
    

Detailed description: 
      Nasal obstruction impairs sleep quality and may predispose to snoring and obstructive sleep
      apnoea (OSA) [1]. Indeed, in healthy subjects, experimental nasal occlusion has been shown to
      elicit obstructive apnoeas [2]. Additionally, in patients with OSA nasal obstruction is
      considered a risk factor for the development of OSA [3].

      Despite the relationship between nasal obstruction and OSA, the therapeutic effect of
      improving nasal airway patency on OSA severity remains a point of conjecture [4]. In fact,
      administration of intranasal corticosteroids has been shown to improve sleepiness and reduce
      the apnoea/hypopnoea index (AHI) in patients with OSA and rhinitis [5], whereas in OSA
      patients with nasal obstruction the use of topical decongestants, external nasal dilators and
      nasal surgery has provided equivocal results [6].

      The present authors have demonstrated a strong correlation between apnoea-hypopnoea index and
      oral/oro-nasal breathing epochs in patients with OSA and normal nasal resistance [7].
      Additionally, Kohler et al [8] have shown that nasal resistance may increase during sleep
      reflecting substantial variability. Therefore, it is plausible to hypothesize that OSA
      patients presenting with normal nasal resistance when they are awake may demonstrate
      increased nocturnal nasal resistance during sleep that may predispose to oral/oro-nasal
      breathing and elicit apnoea/hypopnoeas. Prevention of nocturnal nasal obstruction in such OSA
      patients may decrease oral/oro-nasal breathing and eventually be beneficial for OSA by
      decreasing apnoea/hypopnoeas. Thus, the present study aims to investigate whether the
      pharmacological prevention of nasal obstruction could alter breathing route pattern and lead
      to a decrease in the number of apnoea/hypopnoeas in OSA patients with normal nasal
      resistance.

      The study will include two nasal treatment options. Firstly, a combination of a nasal
      decongestant (tramazoline) with a nasal corticosteroid (dexamethazone). Tramazoline
      (imidazoline derivative) is a nasal decongestant, which attains its maximal effect between 30
      and 210 min after application [9], while nasal dexamethasone can attenuate nasal inflammation
      associated with OSA [10]. Secondly, sodium chloride (0.9% solution).

      OSA patients (AHI>10 events/h) with normal nasal resistance measured in seated and supine
      position with active anterior and posterior rhinomanometry (<3.0 cmH20•L-1•s) will be
      recruited. Exclusion criteria will be considered: 1) recent surgery involving the upper
      airways, 2) central apnoeas more than three per hour or five percent of total apnoeas, 3)
      total sleep time during polysomnographies less than three hours, 4) current treatment with
      nasal decongestants and topical steroids, and 5) upper or lower respiratory tract disease,
      including a history of nasal allergy, and 6) smoking.

      A randomized double-blind, placebo-controlled, cross-over design will be used (Figure 1).
      Every patient will undergo four assessments which will take place 24-48 hours after each
      treatment arm. Every assessment will consist of an overnight polysomnography with concomitant
      measurement of breathing route pattern (oral, nasal, oro-nasal breathing epochs) as
      previously described [7], along with a nasal resistance measurement. After baseline
      assessment and randomization patients of the first group will undergo a one-week therapy with
      nasal tramazoline and dexamethazone, while the patients of the second group will undergo a
      one-week therapy with nasal placebo (sodium chloride, 0.9% solution). The second assessment
      will take place at the end of this one week regimen. A washout period of two weeks will
      follow. Subsequently, the third assessment will take place and next the patients of the first
      group will undergo a one-week therapy with nasal placebo (sodium chloride, 0.9% solution),
      while the patients of the second group will undergo a one-week therapy with nasal tramazoline
      and dexamethazone. Fourth assessment will then follow.

      Figure 1. Study design

      First group: one First group: one week nasal week nasal placebo tramazoline with
      dexamethazone

      2 weeks washout period

      Second group: one Second group: one week nasal placebo week nasaltramazoline with
      dexamethazone

      First Assessment Second Assessment Third Assessment Fourth Assessment
    

Intervention name(s): Nasal tramazoline with dexamethazone; Nasal placebo
Intervention type(s): Drug; Drug
Intervention description(s): Every patient will undergo four assessments. Every assessment will consist of an overnight polysomnography with concomitant measurement of breathing route pattern (oral, nasal, oro-nasal breathing epochs) as previously described [7], along with a nasal resistance measurement. After baseline assessment and randomization patients of the first group will undergo a one-week therapy with nasal tramazoline and dexamethazone, while the patients of the second group will undergo a one-week therapy with nasal placebo (sodium chloride, 0.9% solution). The second assessment will take place at the end of this one week regimen. A washout period of two weeks will follow. Subsequently, the third assessment will take place and next the patients of the first group will undergo a one-week therapy with nasal placebo (sodium chloride, 0.9% solution), while the patients of the second group will undergo a one-week therapy with nasal tramazoline and dexamethazone. Fourth assessment will then follow.; Every patient will undergo four assessments. Every assessment will consist of an overnight polysomnography with concomitant measurement of breathing route pattern (oral, nasal, oro-nasal breathing epochs) as previously described [7], along with a nasal resistance measurement. After baseline assessment and randomization patients of the first group will undergo a one-week therapy with nasal tramazoline and dexamethazone, while the patients of the second group will undergo a one-week therapy with nasal placebo (sodium chloride, 0.9% solution). The second assessment will take place at the end of this one week regimen. A washout period of two weeks will follow. Subsequently, the third assessment will take place and next the patients of the first group will undergo a one-week therapy with nasal placebo (sodium chloride, 0.9% solution), while the patients of the second group will undergo a one-week therapy with nasal tramazoline and dexamethazone. Fourth assessment will then follow.
Intervention MeSH terms: Tramazoline
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment