Efficacy of a Novel MAD in OSA
Condition: Sleep Apnea, Obstructive; Apnea, Obstructive; OSA; OSAH; Obstructive Sleep Apnea; Obstructive Sleep Apnea Syndrome
MeSH terms: Apnea; Sleep Apnea Syndromes; Sleep Apnea, Obstructive
Study type: Interventional

Summary: 
      Oral appliances (OA) have emerged as an alternative to continuous positive airway pressure
      (CPAP) for obstructive sleep apnea (OSA) treatment. The most commonly used OA reduces upper
      airway collapse by advancing the mandible (mandibular advancement devices, MAD).

      There is a strong evidence base demonstrating that MADs improve OSA in the majority of
      patients, including some with more severe disease. However, MADs are not efficacious for all,
      with approximately one-third of patients experiencing no therapeutic benefit. Patients often
      prefer MADs to gold-standard CPAP treatment. Head-to-head trials confirm CPAP is superior in
      reducing OSA parameters on polysomnography; however, this greater efficacy does not
      necessarily translate into better health outcomes in clinical practice. Comparable
      effectiveness of MADs and CPAP has been attributed to higher reported nightly use of MADs,
      suggesting that inferiority in reducing apnoeic events may be counteracted by greater
      treatment adherence.

      The MAD in study, called Bite-Velo Linguale (BVL), features a novel monobloc device including
      a tongue retainer, a suction cavity that maintains the tongue down onto the mouth floor in
      order to prevent it from raising towards the hard palate, and therefore increasing the retro
      lingual aerial space. Its design requires the presence of only four occlusal points, allowing
      for a direct anchorage onto the mandibular bone, thus reducing the risk for occlusal changes,
      tooth loosening and the development of an anterior cross bite, which represent some of the
      major long-term adverse effects of oral appliances.

      MADs are generally well tolerated, although short-term adverse effects during acclimatization
      are common. Long-term dental changes do occur, but these are for the most part subclinical
      and do not preclude continued use. The BVL in study features technological advances aimed at
      preventing long-term dental changes, as well as improving tolerability and easiness of use.
    

Detailed description: 
      The MAD in study features a novel monobloc device including a tongue retainer, a suction
      cavity to push the tongue down onto the mouth floor, thus preventing its lifting towards the
      hard palate, which improves retro lingual dimensions. Its design requires the presence of
      only four occlusal points, allowing for a direct anchorage onto the mandibular bone, thus
      reducing the risk for occlusal changes, tooth loosening and the development of an anterior
      cross bite, which represent the major long-term adverse effects of oral appliances.

      MADs, as well as CPAP, represent the first choice treatment for mild-to-moderate OSAH. In
      several countries, as well as in Switzerland, health insurances cover the costs of MAD
      production in patients with mild-to-moderate OSAH or in severe OSAH patients who did not
      tolerate CPAP previously (as specified in the federal Mittel und Gegenständeliste (MiGeL),
      Position L 23.26.01.00.1).

      Three main novelties justify the experimentation of this new MAD: a monobloc design, the
      combination with a tongue retainer and a potential future lower cost of production compared
      to the devices available on the market today.

      The device will be designed, manufactured and used under the conditions and for the purposes
      intended. Thus, it will not compromise the clinical condition or the safety of patients, or
      the safety and health of users or, where applicable, other persons. Any risks, which may be
      associated with its intended use, constitute acceptable risks when weighed against the
      benefits to the patient and are compatible with a high level of protection of health and
      safety.

      The administration of the device will proceed according to both the essential requirements of
      the European directives concerning medical devices (Annex I and X of directive 93/42/EEC) and
      the clinical practice standards and guidelines provided by the AASM and AASDM. These include
      the obtainment of alginate impression of both jaws and an interocclusal record, with the
      mandible at 50% of its maximal protrusive position. Since no single standard titration
      protocol is available, progressive mandibular advancement will be conducted according to the
      best available medical standard.

      Monocentric, prospective, open-label, interventional, exploratory pilot study.

      Patients aged 18-65 years who received a video-polysomnographic diagnosis of mild-to-moderate
      OSA (AHI between 5/h and 30/h) within three months will be screened and recruited at the
      Sleep and Epilepsy Center in Lugano. An ENT evaluation including a Müller maneuver and a
      calculation of the Mallampati Score must have been performed in order to rule out significant
      ENT comorbidities (See Section 7.1 Eligibility Criteria).

      At Visit 1 (week 1: 7+3 days), performed by either Prof. Manconi or Dr. Chiaro, inclusion and
      exclusion criteria will be checked. Eligible patients will be included in the study.

      Proof that a video-polysomnographic diagnosis of mild-to-moderate OSA was reached and that
      significant oropharyngeal disease was ruled out by means of fibro endoscopic evaluation,
      performed by a trained Ear, Nose & Throat (ENT) specialist in the last three months will be
      obtained.

      During the visit, overall sleep quality and excessive daytime sleepiness will be evaluated by
      means of the Pittsburgh Sleep Quality Index (PSQI) and the Epworth Sleepiness Scale (ESS)
      (See Appendix 2).

      At any time within Visit 1 and 2, (weeks 1 to 2, 14+3 days), the patient will undergo a
      head-CT scan. Patients will be scheduled for a CT scan of the oropharynx region at the
      Radiology Department of the Ospedale Civico of Lugano. CT scans (CT Siemens SOMATOM
      Definition Edge).will be performed in awake supine patients with their heads in a neutral
      position and will be repeated in the same session with and without the MAD. Subsequently,
      post-processing measurements of the upper airway will be calculated with a dedicated CT
      workstation.

      At Visit 2 (week 2: 7+3 days), subjects will undergo odontological evaluation, performed by
      Dr Ciocco. This includes a first general clinical evaluation, the obtainment of alginate
      dental impressions (Blueprint creme, dust-free alginate impression material, manufactured by
      Dentsply® DeTrey GmbH 78467 Konstanz, Germany) with dental impression trays, the calculation
      of the dental facebow with an occlusal fork and of the bite with dental wax casts.

      Weeks 3 to 4 (14+3 days) are the timeframe allotted to medical device production, which will
      be carried out by Mr Frigerio. Dental impressions will be modelled into chalk casts. Both
      casts will be then fixed on a dental articulator, so that different orthodontic measures can
      be calculated and the BVL will be produced out of resin (Palapress, powder+ liquid, Heraeus
      Kulzer GmbH, Grüner Weg 11, D-63450 Hanau) directly on the chalk casts, obtained from the
      patient's dental impression.

      Once roughly finished, the two splints will be held together by means of an integrated
      advancement system composed by two stainless steel positioning holding screws (one left, one
      right) two serrated housing nuts (one left, one right), both produced by Leone SPA, Sesto
      Fiorentino, Italy, as well as two Dolder® system bars (one male, one female, two per side),
      produced by Cendres+Metaux SA, Biel/Bienne, Switzerland. This coupling system enables the
      horizontal (forwards) sliding of the lower splint on the upper splint, thus allowing
      mandibular advancement. The metal and resin parts are glued together with a primer produced
      by SHOFU Dental GmbH, Ratingen, Germany.

      The BVL also features a tongue retainer, which will be completed by small holes on its
      anterior part in order to allow enhanced breathing and saliva excretion.

      The BVL will then be finished, perfected and polished. A unique identification number and the
      BVL trademark will be printed on the BVL.

      See Appendix 1 for technical and commercial details regarding used materials and their
      related available safety data.

      At visit 3 (week 5-6: 7+3 days): the BVL will be then administered at 50% of mandibular
      advancement by Dr Ciocco, based on calculations of the patient's maximal mandibular
      protrusion. Immediate tolerability and side effects (i.e: myofacial pain, temporo-mandibular
      tension) will be checked by means of a semi-structured self-administered questionnaire (See
      Appendix 3) and duly noted.

      If the patient experiences important side effects at this stage, he will discontinue the
      study.

      At Visit 4 (week 7: 7+3 days), Dr Ciocco will perform further mandibular advancement to 60%
      of the calculated maximal mandibular protrusion by activating the integrated advancement
      system. Tolerability, side effects and compliance will be assessed by means of a
      semi-structured self-administered questionnaire (See Appendix 3) and duly noted.

      At Visit 5 (week 8: 7+3 days), Dr Ciocco will perform further mandibular advancement to 70%
      of the calculated maximal mandibular protrusion by again activating the integrated
      advancement system. Tolerability, side effects and compliance will be assessed by means of a
      semi-structured self-administered questionnaire (See Appendix 3) and duly noted.

      At Visit 6 (week 9 to 10, 14+3 days), the patient will undergo VPSG recording and a head-CT
      scan. Patients will be scheduled for a CT scan of the oropharynx region at the Radiology
      Department of the Ospedale Civico of Lugano. CT scans (CT Siemens SOMATOM Definition
      Edge).will be performed in awake supine patients with their heads in a neutral position and
      will be repeated in the same session with and without the MAD. Subsequently, post-processing
      measurements of the upper airway will be calculated with a dedicated CT workstation. At this
      point, tolerability, side effects and compliance will be assessed by means of a
      semi-structured self-administered questionnaire (See Appendix XXX) and duly noted.

      If, at any point from MAD administration (Visit 3) to achievement of 70% mandibular
      protrusion (Visit 5), any serious side effect occurs, the patient will stop mandibular
      advancement and return to the previous level of mandibular protrusion, at which no side
      effects were experienced. He or she will then proceed directly to VPSG and Head-CT and then
      leave the study.

      At the final evaluation (Visit 7, week 11), the patient will meet with the investigator
      again. PSQI and ESS will be administered to assess overall sleep quality and daytime
      sleepiness. Overall tolerability, side effects and compliance will be assessed by means of a
      semi-structured self-administered questionnaire (See Appendix 3) and duly noted. The
      custom-made MAD will be left with the patient free of charge.

      We plan to include 20 study subjects. This study does not comply study groups, comparators or
      placebo. All subjects will receive treatment with MAD. For each patient, as described above,
      we plan a study duration of a maximum of 11 weeks. A shorter duration is foreseen for
      subjects who cannot reach a 70% mandibular advancement because of TMJ tension or for
      dropouts.
    

Intervention name(s): Velo-Lingual Bite (BVL)
Intervention type(s): Device
Intervention description(s): The administration of the device will proceed according to both the essential requirements of the European directives concerning medical devices (Annex I and X of directive 93/42/EEC) and the clinical practice standards and guidelines provided by the AASM and AASDM. These include the obtainment of alginate impression of both jaws and an interocclusal record, with the mandible at 50% of its maximal protrusive position. Since no single standard titration protocol is available, progressive mandibular advancement will be conducted according to the best available medical standard.
Intervention model: Single Group Assignment
Intervention model description: Monocentric, prospective, open-label, interventional, exploratory pilot study.
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: obstructive sleep apnea syndrome; video-polysomnography; mandibular advancement device; oral device; cephalometry