Nasal Tramazoline and Dexamethazone in Obstructive Sleep Apnea (OSA) Patients Tramazoline and (NTD)

Randomized Placebo-controlled Cross-over Trial of the Effect of Nasal Tramazoline With Dexamethasone in Obstructive Sleep Apnoea Patients

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.

Study Overview

• Status: Completed
• Conditions: Obstructive Sleep Apnea Syndrome
• Intervention / Treatment: Drug: Nasal tramazoline with dexamethazone; Drug: Nasal placebo

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

• Study Type: Interventional
• Enrollment (Actual): 23
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Greece
  • Athens, Greece
    • Centre of Sleep Disorders

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. OSA patients (AHI > 10 events/h), and
2. normal nasal resistance measured in seated and supine position with active anterior and posterior rhinomanometry (< 3.0 cmH20•L-1•s).

Exclusion Criteria:

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Nasal placebo; 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.
Active Comparator: nasal spray with tramazoline and dexamethazone	Drug: Nasal tramazoline with dexamethazone; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Apnoea-hypopnoea index	After baseline assessment and randomization first group will undergo a one-week therapy with nasal tramazoline-dexamethazone, while second group will undergo a one-week therapy with nasal placebo. The second assessment will take place at the end of one week regimen. A washout period of two weeks will follow. Subsequently, the third assessment will take place and next first group will undergo a one-week therapy with nasal placebo, while second group will undergo a one-week therapy with nasal tramazoline-dexamethazone. Fourth assessment will then follow.	up to 4 weeks

Collaborators and Investigators

• Sponsor: University of Athens
• Investigators: Principal Investigator: Ioannis Koutsourelakis, MD, University of Athens

Publications and helpful links

General Publications

• Koutsourelakis I, Minaritzoglou A, Zakynthinos G, Vagiakis E, Zakynthinos S. The effect of nasal tramazoline with dexamethasone in obstructive sleep apnoea patients. Eur Respir J. 2013 Oct;42(4):1055-63. doi: 10.1183/09031936.00142312. Epub 2013 Feb 8.

Study record dates

Study Major Dates

• Study Start: April 1, 2010
• Primary Completion (Actual): May 1, 2012
• Study Completion (Actual): May 1, 2012

Study Registration Dates

• First Submitted: March 4, 2012
• First Submitted That Met QC Criteria: May 17, 2012
• First Posted (Estimate): May 18, 2012

Study Record Updates

• Last Update Posted (Estimate): May 18, 2012
• Last Update Submitted That Met QC Criteria: May 17, 2012
• Last Verified: May 1, 2012

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Respiratory Tract Diseases; Respiration Disorders; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Signs and Symptoms, Respiratory; Sleep Apnea Syndromes; Sleep Apnea, Obstructive; Apnea; Physiological Effects of Drugs; Autonomic Agents; Peripheral Nervous System Agents; Sympathomimetics; Tramazoline
• Other Study ID Numbers: UOA-123