Randomized Clinical Trial of Nasal Turbinate Reduction to Improve Continuous Positive Airway Pressure (CPAP) Outcomes for Sleep Apnea

Study Overview
=================
Brief Summary
-----------------
Obstructive sleep apnea occurs in 2-4% of middle age adults and results in significant morbidity and mortality. The first line therapy is provision of continuous positive airway pressure (CPAP) via a nasal mask chronically. Nasal resistance related to nasal turbinate enlargement may compromise CPAP treatment. This randomized double-blind sham-placebo-controlled trial tests the hypothesis that nasal turbinate reduction improves the nasal passage, CPAP use, and sleep apnea quality of life in newly diagnosed sleep apnea patients who are recommended CPAP therapy.

Detailed Description
-----------------
Obstructive sleep apnea syndrome afflicts at least 2 - 4% of adults and is associated with significant morbidity and mortality. Continuous positive airway pressure (CPAP) therapy is the primary treatment for sleep apnea in adults, but non-adherence to CPAP limits its effectiveness. Even with maximal medical therapy, nasal obstruction is common in sleep apnea patients and may hamper both CPAP adherence and efficacy. However, the most common cause of nasal obstruction in sleep apnea patients (turbinate hypertrophy) is surgically correctable. Treatment of nasal obstruction may lead to more successful use of CPAP. The long-term goal of the proposed research is to develop a novel, multi-disciplinary, multi-modal approach to therapy, in order to improve clinically important treatment outcomes for sleep apnea. The short-term objectives of this proposal are to: Quantify the effect of nasal turbinate reduction on the nasal airway; Determine whether turbinate reduction increases CPAP use or efficacy; and Determine whether turbinate reduction positively influences CPAP treatment outcomes. We will employ a single-site, randomized, double-blind, sham-placebo-controlled trial to test the hypotheses that turbinate reduction: increases nasal airway cross-sectional area; increases mean nightly objective CPAP use; and improves sleep apnea quality of life 3 months after CPAP titration. We will use the radiofrequency turbinate reduction surgical technique, which allows ethical randomization and effective blinding. Three, six, and 12 months after turbinate reduction and CPAP titration we will measure the change in the minimal nasal cross-sectional area, level of CPAP use, and improvement in sleep apnea quality of life. Secondary outcomes will capture this treatment's broader impact on the nose, CPAP, and sleep apnea. If turbinate reduction can be shown to improve sleep apnea outcomes through increased use or efficacy of CPAP therapy, this trial will demonstrate the value and effectiveness of a novel, multidisciplinary, combined medical-surgical approach to the management of obstructive sleep apnea syndrome.

Official Title
-----------------
Turbinate Reduction & CPAP Use: A Randomized Blinded OSA (TURBO) Trial

Conditions
-----------------
Sleep Apnea Syndromes, Nasal Obstruction, Turbinate Hypertrophy

Intervention / Treatment
-----------------
* Procedure: Radiofrequency Turbinate Reduction
* Procedure: Sham RF


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Age 18-80 years Newly diagnosed obstructive sleep apnea (apnea-hypopnea index >= 5 events/hour) CPAP therapy recommended Persistent bilateral inferior turbinate hypertrophy American Society of Anesthesiologists Class I-III Ability to give informed consent Ability and willingness to complete the study protocol Fluency in verbal and written English Exclusion Criteria: Previous surgical turbinate treatment Other nasal disorders (i.e. recurrent epistaxis, desiccated or crusted mucosa, severe bilateral obstructing septal deformity, or obstructing polyposis) Active respiratory tract infections Coagulopathy Severe psychiatric comorbidity (taking anti-psychotic medication) American Society of Anesthesiologists Class IV or V Pregnancy No telephone Plans of moving during the study period Known contraindication to lidocaine with epinephrine, oxymetazoline, or acetaminophen

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 1<br>Active RF treatment | Procedure: Radiofrequency Turbinate Reduction<br>* Radiofrequency Turbinate Reduction<br>|
| Sham Comparator: 2<br>Sham RF treatment | Procedure: Sham RF<br>* The steps of the procedure are as follows: 1) application of topical anesthetic to the turbinate mucosa bilaterally; 2) injection of 1.0 ml of lidocaine 1% with epinephrine 1:100,000 with a 30-gauge needle into each inferior turbinate anteriorly; 3) delay five minutes for local anesthetic to take full effect; 4) re-insertion of the anesthetic needle to check for complete anesthesia on one side, and injection of another 1.0 ml of lidocaine 1% with epinephrine 1:100,000 5) placement of the radiofrequency electrode (23-gauge, 1 cm long) into the inferior turbinate; 6) delivery of 300 Joules of radiofrequency energy to the turbinate over 29 seconds (no energy will be delivered in sham procedure)7) placement of a cotton pledget (soaked in oxymetazoline solution 0.05%) against the treatment site 8) repeat steps 3 - 8 for the contra-lateral inferior turbinate; 9) removal of the cotton pledgets after several minutes; and 11) observation of hemostasis.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Nasal minimum cross-sectional area (measured objectively with acoustic rhinometry) |  | Primary outcome at 3 months, secondary outcomes at 6 and 12 months | 
| CPAP use (measured objectively as pressure-on use) |  | Primary outcome at 3 months, secondary outcomes at 6 and 12 months | 
| Sleep Apnea Quality of Life Index (change measured with Then Test technique) |  | Primary outcome at 3 months, secondary outcomes at 6 and 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Secondary Nasal Outcome Measures: peak inspiratory flow, resistance (rhinomanometry), endoscopy, smell identification test, nasal obstruction symptom evaluation (NOSE) scale, and other nasal treatment history |  | 3, 6, and 12 months | 
| Secondary CPAP Outcome Measures: acceptance, subjective tolerance, pressure, leak, residual breathing events (measured by CPAP device) |  | 3, 6, and 12 months | 
| Secondary Clinical Outcome Objective Measures: vigilance (psychomotor vigilance task monitor), blood pressure, and plasma C-reactive protein (cardiovascular risk biomarker) |  | 3, 6, and 12 months | 
| Secondary Clinical Outcome Subjective Measures: Quality of Life Change, Symptoms of Nocturnal Obstruction & Related Events (SNORE-25) Scale, Pittsburgh Sleep Quality Index, Epworth Sleepiness Scale, and Short Form-36 version 2 |  | 3, 6, and 12 months | 
| Adverse events |  | Any time research participant reports and scheduled evaluations at 3, 6, and 12 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Nasal Obstruction, Sleep surgery, Sleep Apnea, Sleep disordered breathing, Turbinate, Radiofrequency, Continuous positive airway pressure, CPAP