Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT03716648 |
| Other study ID # |
18/33/364 |
| Secondary ID |
|
| Status |
Completed |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
May 22, 2019 |
| Est. completion date |
April 7, 2021 |
Study information
| Verified date |
July 2021 |
| Source |
University Hospital, Antwerp |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
In this prospective randomized cross-over trial, 3 different titration procedures will be
compared:
1. titration of the mandibular advancement device (MAD) in the home setting based on both
the physical limits of the patient's mandibular protrusion and the resolution of
subjective complaints, as currently often used in routine clinical practice;
2. an overnight titration PSG using the remotely controlled mandibular positioner (RCMP)
with stepwise mandibular protrusion until respiratory events are reduced and
3. incremental protrusion of the mandible during DISE using the RCMP until upper airway
collapse at all collapsible levels is eliminated.
The aim of this study is to prospectively compare the target protrusion, as well as the
treatment outcome in terms of treatment efficacy, of the 3 different titration protocols.
Description:
After inclusion, each patient will undergo three different titration procedures of the
protrusive mandibular position or target protrusion for the MAD treatment, in a randomized
order: subjective titration, titration during DISE, titration during PSG.
1. Subjective titration:
After fitting the MAD, there is a 1-month period during which the patients get used to
wearing the device and titrate the MAD based on improvement of subjective complaints.
The actual mechanism of titration will be individually trained with each patient.
2. Titration during drug-induced sleep endoscopy (DISE) - DISE-assisted titration:
The DISE will be performed by an ear-nose-throat (ENT)surgeon experienced in DISE in
order to visualize the dose-dependent effect of the mandibular protrusion on the upper
airway collapsibility. The DISE is performed in a semi-dark and silent operating theatre
with the patient lying in supine position. The different collapsible levels of the upper
airway that can be investigated during DISE are the palate (velopharynx), the
oropharynx, the tongue base, the hypopharynx and the epiglottis. The degree of collapse
at each level is reported as none, partial or complete. The pattern of the pharyngeal
collapse during the obstructive events are classified as concentric, anteroposterior
and/or laterolateral. Upon connection of the RCMP to a dedicated laptop, calibration of
the actual versus the software-guided protrusion is verified using the RCMP ruler and
proprietary developed software, to rule out day-to-day variation caused by environmental
factors such as room temperature or humidity. This procedure ensures the mandibular
displacement to be read out correctly from the ruler present at the upper tray fitted
over the tooth arcs. After the calibration, the RCMP-trays are fitted in edge-to-edge
position to avoid excessive muscle tension. A flexible fibreoptic nasendoscope will be
introduced by the ENT surgeon in the awake patient to evaluate the awake upper airway
state. Thereafter, sedation will be induced by intravenous administration of midazolam
(bolus injection of 1.0 to 2.0 mg) and propofol using a target-controlled infusion
system (2.0 to 3.0 μg/mL). The transition to unconsciousness similar to stage 2 sleep is
aimed at and examined by assuring absence of patients' eyelash reflex after stimulation
by means of a gentle brush. Findings are noted using a uniform upper airway scoring
system evaluating level of snoring, presence of apneas and degree of oxygen saturation,
degree and configuration of obstruction(s) and the level of upper airway collapse. When
target sedation is reached, examined by assuring absence of patients' eyelash reflex
after stimulation by means of a gentle brush, the RCMP will be remotely protruded in
increments of 2 mm in response to the visualized upper airway collapse at the different
collapsible levels until a stable upper airway together with absence of desaturations
and snoring is reached. If a stable upper airway in absence of snoring is noted, oxygen
desaturation and apneas are evaluated, and the mandible will be remotely retruded for 1
mm. If the upper airway remains stable, further so-called 'reversed titration' will
continue. This approach will be repeated until the effective target protrusive position
can be determined, defined as the minimal mandibular threshold position corresponding to
a stable upper airway in the absence of snoring, oxygen desaturation and apneas. When a
stable upper airway is reached, the titration procedure will be continued in 0.5 mm
steps, to be as precise as possible. After every protrusive or retrusive movement the
RCMP protrusion will be checked on the RCMP ruler versus the protrusion measured by the
software, assuring correct positioning of the mandible during the upper airway
evaluation.
3. Titration during polysomnography (PSG):
At the start of the PSG, the participant's dental trays are attached to the mandibular
positioner of the RCMP device, and the positioner is calibrated to the PSG system using the
device software. The titration procedure that will be used in this study is previously
described. Once asleep, the patient's mandible will be protruded remotely in 0.5 mm steps in
response to evidence of apneas and/or hypopneas. If an EEG arousal occurs, no further
advancement will be attempted until stable sleep resumes. Stepwise mandibular protrusion will
continue until respiratory events are reduced to normal in all sleep stages, and in both
supine and lateral position, or until maximal protrusion is reached. Afterwards, an
independent researcher will score the PSG together with body position and mandibular position
signals and will predict success or failure with MAD therapy based on the predetermined
interpretative rules. The patient needs to have rapid eye movement (REM) sleep for ≥ 5
minutes in the supine position or in the lateral position, if REM in supine position was not
observed. All REM cycles will be evaluated to identify a minimum 5 minutes' interval where ≤
1 respiratory event occurred. If this is the case, the PSG will be scored as predicted MAD
success for that protrusive position. If not, the PSG will be judged to predict therapeutic
failure. The predicted effective target protrusive position is the minimum protrusive
position that is associated with ≤ 1 respiratory event per 5-minutes REM interval. If the PSG
is scored as predicted success, the predicted effective target protrusive position is
provided to the dentist to start MAD therapy in that position. If the PSG is scored as
predicted failure, an alternative position equal to 75% of maximal protrusion is provided.
A polygraphic evaluation of the MAD efficacy will be planned after each titration procedure.
Furthermore, the patients will be asked to fill out questionnaires regarding snoring, daytime
sleepiness (Epworth Sleepiness Scale, ESS), fatigue (Checklist Individual Strength, CIS20R)
and side effects of the MAD treatment.
A wash-out period of one week is inserted between the polygraphic evaluation of the
protrusive position obtained during a titration procedure and the start of the next titration
procedure.
