Clinical trial NCT02781701: Tongue Protrusion Force: A Pilot Study
Official title: Tongue Protrusion Force: A Pilot Study
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: NA
Conditions: Obstructive Sleep Apnea (OSA)
Lead sponsor: Weill Medical College of Cornell University
Sponsor class: OTHER
Collaborators: name: Cornell University
First posted: 2016-05-24
Enrollment: 0
Sex: ALL
Minimum age (years): 21
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: From Weill Cornell Medical College Center for Sleep Medicine, the investigators will recruit patients (N = 25) with previously documented moderate to severe OSA. They will receive an all-night in-home sleep study to document the severity of their OSA immediately before starting the training regimen. Scales and questionnaires measuring sleepiness, snoring, fatigue, and insomnia will be administered prior to starting the training and repeated after six weeks of training. Subjects may be removed from the study due to failing to adhere to the training regimen at anytime via remote data monitoring. The principal measure of the efficacy of the treatment will be the change in RDI, the number of abnormal breathing events per hour of sleep.

Detailed description: Obstructive sleep apnea (OSA) is a condition characterized by temporary diminutions or cessations of breathing caused by repetitive collapse of the upper airway (UA) during sleep (1). OSA is a common disorder associated with abnormalities in pharyngeal anatomy and physiology in which the muscles of the airway, which normally relax during sleep, fail to provide sufficient dilatory force to balance the contractive force from inspiratory activity (2). This force imbalance serves to either partially or completely collapse the UA, thereby preventing sufficient air from reaching the lungs. These pauses in breathing lead to blood oxygen desaturation and induce neurological arousal resulting in sleep disruption and fragmentation. The cycle of airway collapse and arousal can repeat hundreds of times per night (1). According to the National Sleep Foundation, OSA affects 18-22 million Americans, 80% of whom are undiagnosed. OSA is more prevalent among overweight and older individuals and those with reduced muscle tone, skeletal anomalies such as micrognathia or retrognathia, and airways crowded by redundant or enlarged soft tissue structures.

OSA is associated with significant physiological and psychological problems. OSA results in excessive daytime sleepiness, fatigue, memory impairment, and reduced reaction time, increasing the risk for motor vehicle (3) and workplace (4) accidents. In addition, OSA sufferers face increased cardiovascular risk including hypertension, heart disease, and stroke (5). OSA has even recently been linked to increased cancer incidence (6) and mortality (7), presumably through hypoxia-induced angiogenesis.

On the morning of December 1, 2013, a Metro-North passenger train derailed in the Bronx. The accident killed 4 passengers, injured 61, and caused $9 million worth of damage. Investigators determined human error was to blame: the train engineer admitted that before reaching the curve he had "gone into a daze," allowing the train to travel at three times the posted speed limit (8). A medical examination conducted after the accident diagnosed the train engineer with OSA, which hampered his ability to fully adjust his sleep patterns to the morning shift he had begun working just two weeks prior to the accident (9).

The Harvard Medical School released a report in 2010 entitled, "The Price of Fatigue: The Surprising Economic Costs of Unmanaged Sleep Apnea," in which it estimated the annual economic cost of moderate to severe OSA in the United States to be $65-165B (compared to $60B for drunk driving and $150B for not wearing seatbelts), including $10-40B in OSA-related traffic accidents and $5-20B in OSA-related workplace accidents (10).

Existing treatments for OSA include lifestyle modifications (11) such as weight loss, position restriction, and avoidance of muscle relaxants such as alcohol and benzodiazepine drugs. Oral appliances including mandibular advancement devices and tongue retaining devices have been increasingly employed. OSA is also treated through surgery, including tonsillectomy and uvulopalatopharyngeoplasty (UPPP) to reduce tissue crowding of the UA lumen, genioglossal advancement, and maxillomandibular advancement. The most widespread and generally effective treatment for OSA, however, remains the use of various devices for maintaining positive airway pressure (PAP) such as Continuous Positive Airway Pressure (CPAP), BiLevel Positive Airway Pressure (BiPAP), and Autotitrating (AutoPAP) devices.

CPAP and related treatments are both costly and cumbersome. 40-60% of patients prescribed CPAP fail to adhere to the treatment (12; 13; 14). Patients cite comfort and lifestyle factors (sensation of claustrophobia, dry mouth, ill-fitting mask, and lack of portability of the system precluding use during travel) as reasons for abandoning treatment (15; 16). Benign Prostatic Hypertrophy (BPH), with accompanying nocturia, has also been associated with noncompliance with CPAP among older men (17). Poor compliance with CPAP is prompting the search for alternative forms of treatment for OSA.

The Genioglossus (GG), which makes up most of the body of the tongue, is the major muscle responsible for protruding the tongue and is the major UA dilator that opposes collapsing force in the pharynx upon inspiration. Reduced UA dilator force in sleep is posited to contribute to the collapse of the pharynx in OSA (Schwartz 2001). A number of controlled studies have demonstrated that strengthening the GG can result in clinically significant reductions of OSA severity.

In a randomized controlled trial (RCT) of OSA patients (18), a group that performed oropharyngeal exercises for 30 minutes a day for three months reduced the average apnea hypopnea index (AHI, the number of apnea and hypopnea events per hour of sleep) by almost 35% (22.4 to 14.7, P \< 0.05). The exercises consisted of isometric and isotonic exercises involving the tongue. Another RCT (19) designed to increase UA dilator muscle strength demonstrated that playing the didgeridoo (an aboriginal wind instrument) six times per week for an average of 25 minutes per day over four months decreased average AHI by almost 50% (22.3 to 11.6, P \< 0.01). Electrical stimulation of the hypoglossal nerve (which innervates the GG) also promotes UA patency during sleep. Hypoglossal stimulation reduced UA resistance in both healthy persons and subjects with OSA and reduced AHI in OSA subjects by over 50% (20).

II. Aims

The investigators assert that training the GG muscle while awake will serve to dilate the pharyngeal pathway - restriction of which results in obstructive apnea - during sleep. If confirmed, the investigators will have developed an effective behavioral treatment for OSA. The investigators anticipate it being an attractive alternative for OSA patients who are unable to acclimate to CPAP or adhere to its use for comfort or lifestyle reasons.

This IRB approved clinical study is designed to determine both an effective training regimen to increase GG muscle strength as well as obtain preliminary data on the effect of tongue protrusive force training (TPFT) on OSA. In this study, the investigators will use subjects with moderate to severe OSA. OSA severity will be assessed with a sleep study conducted prior to beginning the training regimen. After six weeks of daily training, OSA severity will be measured again with a follow-up sleep study.

Eligibility criteria: Inclusion Criteria:

1. Age: 21 to 70
2. At home confirmation of moderate to severe OSA (AHI 15-60)
3. BMI less than or equal to 35
4. Not currently on a weight loss plan and no intention of beginning a weight loss regimen during the duration of the study
5. If not currently treated for OSA (AHI 15-20), not planning on starting treatment for OSA during the duration of the study
6. Willing to have a diagnostic sleep study before the training
7. Willing to have a diagnostic sleep study after the training
8. Willing to perform tongue training exercises twice daily for 6 weeks
9. Willing to keep a sleep diary

Exclusion Criteria:

1. Dental problems, e.g., less than a full complement of front teeth, loose front teeth, brittle teeth, by history
2. Temporomandibular joint (TMJ) disorder by history
3. Jaw, neck, or facial muscle pain or discomfort by history
4. Consumes more than one alcoholic beverage per day and unwilling to reduce alcohol consumption to no more than one alcoholic beverage per day (muscle relaxant)
5. On benzodiazepine medication (or specific muscle relaxant)
6. Sleeps less than 5 hours per night on average (sleep deprivation can weaken UA)
7. Pregnant
8. Has had an upper airway surgical procedure for sleep apnea below the level of the nasopharynx
9. Non-English speaker or illiterate

Primary outcomes:
measure: RDI
timeFrame: Six weeks
Secondary outcomes:
measure: TPFmax
timeFrame: Six Weeks
measure: AHI
timeFrame: Six Weeks
measure: dur50%
timeFrame: Six weeks
Other outcomes:
Locations:
city: New York
country: United States
facility: Weill Cornell Medical College Center for Sleep
state: New York
Study officials:
affiliation: Weill Medical College of Cornell University
name: Matthew Ebben, Ph. D.
role: PRINCIPAL_INVESTIGATOR
References:
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