Accuracy of the Sensory Test Using the Laryngopharyngeal Endoscopic Esthesiometer in Obstructive Sleep Apnea

Sponsor

Fundación Neumologica Colombiana (Other)

Overall Status

Recruiting

CT.gov ID

NCT03109171

Collaborator

Universidad de la Sabana (Other), Instituto Colombiano para el Desarrollo de la Ciencia y la Tecnología (COLCIENCIAS) (Other)

117

Enrollment

Locations

Arms

46.9

Anticipated Duration (Months)

58.5

Patients Per Site

1.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This is a prospective double blinded randomized crossover controlled trial aiming at validating the measurement of laryngopharyngeal mechanosensitivity in patients with suspected OSA using a recently developed laryngopharyngeal endoscopic esthesiometer and rangefinder (LPEER).

Subjects will be recruited from patients with suspected OSA referred for baseline polysomnography to a university hospital sleep laboratory. Intra- and inter-rater reliability will be evaluated using the Bland-Altman's limits of agreement plot, the intraclass correlation coefficient, and the Pearson or Spearman correlation coefficient, depending on the distribution of the variables. Diagnostic accuracy will be evaluate plotting Receiver-operating-characteristic-curves (ROC-curves) using as reference standard basal polysomnogram. The sensory threshold values for patients with mild, moderate, and severe OSA, will be determined and compared using ANOVA or Kruskal Wallis test, depending on the distribution of the variables.

Condition or Disease	Intervention/Treatment	Phase
Sleep Apnea, Obstructive Larynx Sensory Disorder	Other: Laryngopharyngeal sensory test	N/A

Detailed Description

INTRODUCTION:

Obstructive sleep apnea-hypopnea syndrome (OSA) patients might have varying degrees of laryngopharyngeal mechanical hyposensitivity; however, these findings come from studies performed with methods having weak inter-rater reliability and accuracy evidence.

The purpose of this study is to validate the measurement of laryngopharyngeal mechanosensitivity in patients with OSA using a recently developed laryngopharyngeal endoscopic esthesiometer and rangefinder (LPEER). The LPEER includes an air-pulse generator and an endoscopic laser rangefinder and works coupled to a conventional fiberoptic endoscope. This device generates air-pulses ranging from 0.04 mN to 16.5 mN in order to cover a wide range of laryngopharyngeal reflexes and sensory thresholds. Depending on the reflex or sensory threshold to be explored the LPEER is configured to deliver a sequence of 10 air-pulses of different intensity.

METHODS:

The study will be prospective, double blinded, and with a randomized and crossover assignment of the raters.

Subjects will be recruited from patients with suspected OSA referred for baseline polysomnography to a sleep laboratory of a tertiary care university hospital. They will undergo a laryngopharyngeal sensory test using the LPEER, which includes measurement of the thresholds for the velopharyngeal, hypopharyngeal and aryepiglottic fold psychophysical sensitivity.

Intra- and inter-rater reliability will be evaluated using the Bland-Altman's limits of agreement plot, the intraclass correlation coefficient, and the Pearson or Spearman correlation coefficient, depending on the distribution of the variables.

Diagnostic accuracy will be evaluate plotting ROC-curves using as reference standard basal polysomnogram. The sensory threshold values for patients with mild, moderate, and severe OSA, will be determined and compared using ANOVA or Kruskal Wallis test, depending on the distribution of the variables.The discriminative capacity as well as correlations between laryngopharyngeal sensory thresholds and OSA severity indexes will be explored in subgroups of subjects with normal and abnormal sensation. The relationship between sensory thresholds and OSA severity indexes will be explored by linear equations as well as by second- and higher-order polynomial equations.

The laryngopharyngeal endoscopic esthesiometer and rangefinder (LPEER), could be a new tool for the evaluation and monitoring of laryngopharyngeal sensory involvement in patients with OSA, which, if proved valid, could help to increase the knowledge about the pathophysiological mechanisms of this condition and potentially help finding new therapeutic interventions for OSA.

ETHICS:

This study will follow the Declaration of Helsinki principles and national legal regulations about research in human subjects. The protocol was approved by the Institutional Review Board of Fundacion Neumologica Colombiana and all recruited subjects will provided a signed informed consent.

DISSEMINATION:

The results will be disseminated through conference presentations and peer-reviewed publication.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

117 participants

Allocation:

Randomized

Intervention Model:

Crossover Assignment

Intervention Model Description:

Subjects participating in the inter-rater reliability evaluation will be evaluated by two raters, an expert and a non-expert rater, each rater performing two measurements of laryngopharyngeal sensory thresholds (ST) two times at each side (right and left) of the corresponding laryngopharyngeal structure. All other subjects, participating in the accuracy evaluation, will be evaluated by only one expert rater who will perform three measurements of laryngopharyngeal ST per subject. The varying degrees of rater experience aims to reproduce common scenarios when a new technique (like the measurement of laryngopharyngeal mechanosensitivity) is introduced to clinical practice. The two raters will measure the ST sequentially and in a randomized cross-over design in each subject (the order in which each rater intervenes will be randomized) aiming that the sensory tests be started an equal number of times by an expert rater and non-expert rater.Subjects participating in the inter-rater reliability evaluation will be evaluated by two raters, an expert and a non-expert rater, each rater performing two measurements of laryngopharyngeal sensory thresholds (ST) two times at each side (right and left) of the corresponding laryngopharyngeal structure. All other subjects, participating in the accuracy evaluation, will be evaluated by only one expert rater who will perform three measurements of laryngopharyngeal ST per subject. The varying degrees of rater experience aims to reproduce common scenarios when a new technique (like the measurement of laryngopharyngeal mechanosensitivity) is introduced to clinical practice. The two raters will measure the ST sequentially and in a randomized cross-over design in each subject (the order in which each rater intervenes will be randomized) aiming that the sensory tests be started an equal number of times by an expert rater and non-expert rater.

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Masking Description:

The allocation sequence, determining which rater (expert vs non-expert) intervenes first or second, will be concealed using the SNOSE strategy (sequentially numbered opaque sealed envelopes). One of the authors (ARB), who has not competing interests will generate the allocation sequence and conceal it in envelopes. While the first rater measures the sensory thresholds (ST) the second rater will be at a different room for blinding purposes. There will be no communication about the testing results between the two raters nor the staff who are helping the testing performance. To mask the values of the ST, air pulses will be identified by a random combination of three letters instead of by the intensity levels corresponding to the air pulses. The raters will not know the intensity corresponding to each letter combination. At the end of the test, an assistant will replace the letters corresponding to the ST values by the intensity levels of the air pulses in units of force (millinewtons)

Primary Purpose:

Diagnostic

Official Title:

Accuracy of the Sensory Test Performed Using the Laryngopharyngeal Endoscopic Esthesiometer and Rangefinder in Patients With Suspected Obstructive Sleep Apnoea Hypopnea (OSA): a Prospective Double-blinded, Randomised, Pilot Study

Actual Study Start Date :

Jan 1, 2018

Anticipated Primary Completion Date :

Sep 30, 2021

Anticipated Study Completion Date :

Nov 30, 2021

Arms and Interventions

Arm	Intervention/Treatment
Other: Expert rater Pulmonologist or Otolaryngologist with experience in laryngopharyngeal sensory evaluation: who has made more than 50 laryngopharyngeal sensory tests.	Other: Laryngopharyngeal sensory test The sensory measurements will include thresholds for psychophysical sensory thresholds at the velopharynx, hypopharynx and aryepiglottic folds
Other: Non-expert rater Pulmonologist or Otolaryngologist inexperienced in laryngopharyngeal sensory evaluation: who has made minimum 5 and maximum 50 laryngopharyngeal sensory tests. Pulmonologist fellow who has completed the training provided for a Pulmonologist Fellow in bronchoscopy and who has performed minimum 5 and maximum 50 laryngopharyngeal sensory testing.	Other: Laryngopharyngeal sensory test The sensory measurements will include thresholds for psychophysical sensory thresholds at the velopharynx, hypopharynx and aryepiglottic folds

Arm

Intervention/Treatment

Other: Expert rater

Pulmonologist or Otolaryngologist with experience in laryngopharyngeal sensory evaluation: who has made more than 50 laryngopharyngeal sensory tests.

Other: Laryngopharyngeal sensory test

The sensory measurements will include thresholds for psychophysical sensory thresholds at the velopharynx, hypopharynx and aryepiglottic folds

Other: Non-expert rater

Pulmonologist or Otolaryngologist inexperienced in laryngopharyngeal sensory evaluation: who has made minimum 5 and maximum 50 laryngopharyngeal sensory tests. Pulmonologist fellow who has completed the training provided for a Pulmonologist Fellow in bronchoscopy and who has performed minimum 5 and maximum 50 laryngopharyngeal sensory testing.

Other: Laryngopharyngeal sensory test

The sensory measurements will include thresholds for psychophysical sensory thresholds at the velopharynx, hypopharynx and aryepiglottic folds

Outcome Measures

Primary Outcome Measures

Velopharynx psychophysical sensory threshold [15 days]
Sensitivity threshold at the velopharynx in millinewtons (mN).
Hypopharynx psychophysical sensory threshold [15 days]
Sensitivity threshold at the hypopharynx in millinewtons (mN).
Aryepiglottic fold psychophysical sensory threshold [15 days]
Sensitivity threshold at the aryepiglottic folds in millinewtons (mN).

Secondary Outcome Measures

Apnea Hypopnea Index [15 days]
Number of apneas and hypopneas per hour reported in polysomnography, according to the American Academy of Sleep Medicine criteria.
Oxygen desaturation index [15 days]
Number of desaturation episodes by pulse oximetry (SpO2%) (>3% fall in SpO2%) per hour reported in polysomnography, according to the American Academy of Sleep Medicine criteria.
T90 [15 days]
Time spent at oxygen saturation below 90% by pulse oximetry
Adverse Events [15 days]
Any adverse event potentially related to the laryngopharyngeal sensory test, including pain, gagging, discomfort, laryngospasm, syncope or pre-syncope, epistaxis, need for observation or referral to emergency room or hospitalization.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

Patients being 18 years old or more referred to the sleep laboratory of a tertiary care university hospital for a baseline polysomnography for suspected OSA.

Exclusion Criteria:

Anticoagulation (though not a contraindication for the endoscopic laryngopharyngeal sensory test, anticoagulation is an exclusion criteria for this validation study in order to keep it a minimal-risk study).
Bleeding diathesis.
Basal awake oxygen saturation by pulse oximetry below 88%.
Not agree to participate in the study.
Glasgow coma scale below of 15 (to avoid confusion with involvement of laryngopharyngeal reflexes due to neurological disease accompanied by decreased level of consciousness).
Baseline polysomnography that does not meet validity criteria to be interpreted (according to the American Academy of Sleep Medicine).
Baseline polysomnography performed more than 15 days before the sensory testing. Ordinarily, the sensory testing will be performed the same day or the next day of baseline polysomnography.
More than 5% of total apnoea events being of central origin.
History of maxillofacial or pharyngeal surgery (to avoid confusion with involvement of laryngopharyngeal reflexes due to surgery in this region).
Laryngopharyngeal tract malignancies (to avoid confusion with involvement of laryngopharyngeal reflexes due to tumours).
Central Nervous System (CNS) surgery in the last three months or that has left neurological sequelae (to avoid confusion with involvement of laryngopharyngeal reflexes due to sequelae of CNS surgery).
Traumatic brain injury in the last three months or more than three month with neurological sequelae.
History of active neuromuscular disease that affects the muscles of head and neck or with sequels present at the time of the sensory testing (to avoid confusion with involvement of laryngopharyngeal reflexes due to neuromuscular disease).
History of cerebrovascular disease (to avoid confusion with dysphagia or sensory compromise secondary to cerebrovascular disease).
Diabetes (to avoid confusion with diabetic neuropathy that compromises the laryngopharyngeal region).
Chronic use of systemic corticosteroids at a dose greater or equal to 20 mg per day of prednisone or equivalent (to avoid confusion with steroid myopathy that compromises the laryngopharyngeal region).
Upper respiratory tract infection within 15 days prior to the testing (to avoid confusion with neuropathy associated with respiratory viral disease that compromises the laryngopharyngeal region).
Patient's inability to cooperate during the examination (to avoid measurement error caused by the lack of cooperation of the patient).