Oropharyngeal Exercises and Post-Stroke Obstructive Sleep Apnea

Stroke Clinical Trial

Official title:

Strengthening Oropharyngeal Muscles as a Novel Approach to Treat Obstructive Sleep Apnea After Stroke: A Randomized Feasibility Study

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04212260
• Other study ID #: 313-2018
• Status: Completed
• Phase: N/A
• Start date: April 1, 2019
• Est. completion date: December 9, 2022

Study information

• Verified date: April 2023
• Source: Sunnybrook Health Sciences Centre
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study evaluates the feasibility and effectiveness of an oropharyngeal exercise (O-PE) regimen in treating post-stroke obstructive sleep apnea, as an alternative therapy to continuous positive airway pressure (CPAP). Eligible patients will be randomized (1:1) to treatment using a pre-specified schedule of O-PEs vs. a sham control arm.

Description:

BACKGROUND Obstructive sleep apnea (OSA) is characterized by recurrent obstruction of the upper airway during sleep due to intermittent loss of pharyngeal dilator muscle tone. OSA is both a risk factor for stroke, as well as a common post-stroke co-morbidity with approximately 72% of patients with stroke or transient ischemic attack (TIA) having OSA. Post-stroke OSA is linked to post-stroke, fatigue, which is a top research priority for stroke patients. Moreover, post-stroke OSA is associated with greater mortality, a higher risk of recurrent stroke, poorer cognition and lower functional status. In addition, stroke patients with OSA spend significantly longer times in rehabilitation and in acute care hospitals. Since OSA has a significant impact on the health of stroke patients, it is imperative that effective treatments are used to assist patients. Continuous positive airway pressure (CPAP) is the gold standard treatment for patients with moderate to severe OSA. However, despite having been demonstrated to improve post-stroke cognition, motor and functional outcomes,and overall quality of life, rates of CPAP adherence are low. Reasons for poor post-stroke CPAP adherence are multi-factorial and often not easily modifiable. Overall, there is a major clinical need to develop an alternative effective and well-tolerated treatment for OSA.

Oro-pharyngeal exercises (O-PEs) are commonly used by speech-language pathologists to improve oro-motor strength and range of motion and serve as a promising alternative approach to treat OSA. For example, in a randomized controlled trial in which patients with moderate OSA underwent 3 months of daily exercises focusing on strengthening oro-pharyngeal musculature, OSA severity and symptoms were demonstrated to be significantly reduced compared to sham exercises.Similarly, use of the didgeridoo, a wind instrument that strengthens muscles of the upper airway, has also been demonstrated to reduce OSA severity.

METHODS Research Question: Is a randomized controlled trial (RCT) of an O-PE regimen in post-stroke OSA feasible?

Primary Objective: To examine whether an RCT of an O-PE regimen is feasible in stroke patients with OSA who are unable to tolerate CPAP. (i) The O-PE regimen will be considered feasible if >80% of enrolled patients complete >80% of the study exercises. (ii) We will also track the monthly number of eligible vs. recruited patients from Dr. Boulos' stroke and sleep disorders clinic. Hypothesis: An RCT of an O-PE regimen in post-stroke OSA will be feasible in that >80% of enrolled patients will complete >80% of the study exercises.

Secondary Objectives: To explore whether an O-PE regimen, compared to sham activities, might be effective in (i) improving various objective sleep metrics (i.e. OSA severity and nocturnal oxygen saturation), (ii) improving various measures of oropharyngeal physiology and function (i.e. oro-pharyngeal deficits and dysarthria, tongue/lip/jaw weakness, and oro-facial kinematics), and (iii) enhancing self-reported sleep-related symptoms. Hypothesis: Compared to the sham activities, O-PEs will positively influence the outcomes noted above.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 33
• Est. completion date: December 9, 2022
• Est. primary completion date: December 9, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A and older

Eligibility

Inclusion Criteria:

• Imaging-confirmed stroke or stroke specialist-diagnosed transient ischemic attack (TIA)

• Prior diagnosis of OSA by a physician at any time in the past.

• Unable to tolerate CPAP after a 2-week trial of CPAP

Exclusion Criteria:

• BMI > 40 kg/m2

• The presence of conditions known to compromise the accuracy of portable sleep monitoring, such as moderate to severe pulmonary disease or congestive heart failure.

• Oxygen therapy (e.g. nasal prongs), a nasogastric tube, or other medical device that would interfere with the placement of the home sleep apnea test

• Cranial malformations/nasal obstruction

• Significant depressive symptoms

• Regular use of hypnotic medications

• Other neuromuscular diseases or conditions affecting oropharyngeal muscles

• Montreal Cognitive Assessment (MoCA) < 18

• Aphasia

• Oral or apraxia of speech

Related Conditions & MeSH terms

• Apnea
• Ischemic Attack, Transient
• Sleep Apnea Syndromes
• Sleep Apnea, Obstructive
• Stroke
• Transient Ischemic Attack

Intervention

Behavioral:
• Oropharyngeal exercises
Oro-pharyngeal exercises that improve oro-pharyngeal and tongue strength. Instructions will be delivered via a tablet-based app.
• Sham control
Simple mouth movements that have no impact of oro-pharyngeal strength. Instructions will be delivered via a tablet-based app.

Locations

Country	Name	City	State
Canada	Sunnybrook Health Sciences Centre	Toronto	Ontario

Sponsors (5)

Lead Sponsor	Collaborator
Sunnybrook Health Sciences Centre	Sunnybrook Research Institute, Toronto Rehabilitation Institute, Unity Health Toronto, University of Toronto

Country where clinical trial is conducted

Canada, 

References & Publications (19)

Aaronson JA, Hofman WF, van Bennekom CA, van Bezeij T, van den Aardweg JG, Groet E, Kylstra WA, Schmand B. Effects of Continuous Positive Airway Pressure on Cognitive and Functional Outcome of Stroke Patients with Obstructive Sleep Apnea: A Randomized Controlled Trial. J Clin Sleep Med. 2016 Apr 15;12(4):533-41. doi: 10.5664/jcsm.5684. — View Citation

Aloia MS, Arnedt JT, Riggs RL, Hecht J, Borrelli B. Clinical management of poor adherence to CPAP: motivational enhancement. Behav Sleep Med. 2004;2(4):205-22. doi: 10.1207/s15402010bsm0204_3. — View Citation

Annoni JM, Staub F, Bogousslavsky J, Brioschi A. Frequency, characterisation and therapies of fatigue after stroke. Neurol Sci. 2008 Sep;29 Suppl 2:S244-6. doi: 10.1007/s10072-008-0951-0. — View Citation

Arzt M, Young T, Finn L, Skatrud JB, Bradley TD. Association of sleep-disordered breathing and the occurrence of stroke. Am J Respir Crit Care Med. 2005 Dec 1;172(11):1447-51. doi: 10.1164/rccm.200505-702OC. Epub 2005 Sep 1. — View Citation

Bradley TD, Floras JS. Obstructive sleep apnoea and its cardiovascular consequences. Lancet. 2009 Jan 3;373(9657):82-93. doi: 10.1016/S0140-6736(08)61622-0. Epub 2008 Dec 26. — View Citation

Chai-Coetzer CL, Luo YM, Antic NA, Zhang XL, Chen BY, He QY, Heeley E, Huang SG, Anderson C, Zhong NS, McEvoy RD. Predictors of long-term adherence to continuous positive airway pressure therapy in patients with obstructive sleep apnea and cardiovascular disease in the SAVE study. Sleep. 2013 Dec 1;36(12):1929-37. doi: 10.5665/sleep.3232. — View Citation

Colelli DR, Kamra M, Rajendram P, Murray BJ, Boulos MI. Predictors of CPAP adherence following stroke and transient ischemic attack. Sleep Med. 2020 Feb;66:243-249. doi: 10.1016/j.sleep.2018.10.009. Epub 2018 Oct 24. — View Citation

Good DC, Henkle JQ, Gelber D, Welsh J, Verhulst S. Sleep-disordered breathing and poor functional outcome after stroke. Stroke. 1996 Feb;27(2):252-9. doi: 10.1161/01.str.27.2.252. — View Citation

Guimaraes KC, Drager LF, Genta PR, Marcondes BF, Lorenzi-Filho G. Effects of oropharyngeal exercises on patients with moderate obstructive sleep apnea syndrome. Am J Respir Crit Care Med. 2009 May 15;179(10):962-6. doi: 10.1164/rccm.200806-981OC. Epub 2009 Feb 20. — View Citation

Johnson KG, Johnson DC. Frequency of sleep apnea in stroke and TIA patients: a meta-analysis. J Clin Sleep Med. 2010 Apr 15;6(2):131-7. — View Citation

Kaneko Y, Hajek VE, Zivanovic V, Raboud J, Bradley TD. Relationship of sleep apnea to functional capacity and length of hospitalization following stroke. Sleep. 2003 May 1;26(3):293-7. doi: 10.1093/sleep/26.3.293. — View Citation

Kim HD, Choi JB, Yoo SJ, Chang MY, Lee SW, Park JS. Tongue-to-palate resistance training improves tongue strength and oropharyngeal swallowing function in subacute stroke survivors with dysphagia. J Oral Rehabil. 2017 Jan;44(1):59-64. doi: 10.1111/joor.12461. — View Citation

Mackenzie C, Muir M, Allen C, Jensen A. Non-speech oro-motor exercises in post-stroke dysarthria intervention: a randomized feasibility trial. Int J Lang Commun Disord. 2014 Sep-Oct;49(5):602-17. doi: 10.1111/1460-6984.12096. Epub 2014 May 29. — View Citation

Martinez-Garcia MA, Soler-Cataluna JJ, Ejarque-Martinez L, Soriano Y, Roman-Sanchez P, Illa FB, Canal JM, Duran-Cantolla J. Continuous positive airway pressure treatment reduces mortality in patients with ischemic stroke and obstructive sleep apnea: a 5-year follow-up study. Am J Respir Crit Care Med. 2009 Jul 1;180(1):36-41. doi: 10.1164/rccm.200808-1341OC. Epub 2009 Apr 30. — View Citation

McEvoy RD, Antic NA, Heeley E, Luo Y, Ou Q, Zhang X, Mediano O, Chen R, Drager LF, Liu Z, Chen G, Du B, McArdle N, Mukherjee S, Tripathi M, Billot L, Li Q, Lorenzi-Filho G, Barbe F, Redline S, Wang J, Arima H, Neal B, White DP, Grunstein RR, Zhong N, Anderson CS; SAVE Investigators and Coordinators. CPAP for Prevention of Cardiovascular Events in Obstructive Sleep Apnea. N Engl J Med. 2016 Sep 8;375(10):919-31. doi: 10.1056/NEJMoa1606599. Epub 2016 Aug 28. — View Citation

Pollock A, St George B, Fenton M, Firkins L. Top ten research priorities relating to life after stroke. Lancet Neurol. 2012 Mar;11(3):209. doi: 10.1016/S1474-4422(12)70029-7. No abstract available. — View Citation

Puhan MA, Suarez A, Lo Cascio C, Zahn A, Heitz M, Braendli O. Didgeridoo playing as alternative treatment for obstructive sleep apnoea syndrome: randomised controlled trial. BMJ. 2006 Feb 4;332(7536):266-70. doi: 10.1136/bmj.38705.470590.55. Epub 2005 Dec 23. — View Citation

Ryan CM, Bayley M, Green R, Murray BJ, Bradley TD. Influence of continuous positive airway pressure on outcomes of rehabilitation in stroke patients with obstructive sleep apnea. Stroke. 2011 Apr;42(4):1062-7. doi: 10.1161/STROKEAHA.110.597468. Epub 2011 Mar 3. — View Citation

Yaggi HK, Concato J, Kernan WN, Lichtman JH, Brass LM, Mohsenin V. Obstructive sleep apnea as a risk factor for stroke and death. N Engl J Med. 2005 Nov 10;353(19):2034-41. doi: 10.1056/NEJMoa043104. — View Citation

* Note: There are 19 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of enrolled participants completing >80% of the study exercises	The study exercise regimen will be deemed feasible if >80% of enrolled patients complete >80% of the study exercises. Patient adherence with study exercises in both treatment arms will be recorded (in minutes) via use of the App that will deliver the oropharyngeal exercises/sham exercises. Completion of >80% of the study exercises would be indicated by >720 recorded minutes (if post-training visit is after 6 weeks) or >1200 recorded minutes (if post-training visit is after 10 weeks).	6-10 weeks (post-training)
Secondary	OSA severity (as measured by the apnea-hypopnea index)	Measured by the apnea-hypopnea index (AHI). AHI quantifies the number of apneas and hypopneas per hour of sleep. It will be measured using a home sleep monitor that has been validated for use in the stroke population.	Baseline, 6-10 weeks (post-training), and 10-14 weeks (retention)
Secondary	Lowest oxygen desaturation	Lowest oxygen desaturation will be measured using a home sleep monitor that has been validated for use in the stroke population.	Baseline, 6-10 weeks (post-training), and 10-14 weeks (retention)
Secondary	Oro-pharyngeal deficits and dysarthria (as measured by the second version of Frenchay Dysarthria Assessment)	The second version of Frenchay Dysarthria Assessment (FDA-2) is divided into 7 sections: reflexes, respiration, lips, palate, laryngeal, tongue, and intelligibility, each containing several individual items. Each item is rated on a scale from "0" to "7", where "0" means normal for age, and "7" means unable to undertake task/movement/sound. The total score of the 7 sections will determine the severity of dysarthria.	Baseline, 6-10 weeks (post-training), and 10-14 weeks (retention)
Secondary	Tongue/lip/jaw weakness	Measured by the Iowa Oral Performance Instrument & Flexiforce (max pressure, endurance)	Baseline, 6-10 weeks (post-training), and 10-14 weeks (retention)
Secondary	Oro-facial kinematic capacity	Oro-facial kinematic capacity is defined by the range of facial motions (in mm) for lips and jaw, assessed during a standardized series of oro-motor tasks (e.g. Maximum mouth opening, syllable repetition)	Baseline, 6-10 weeks (post-training), and 10-14 weeks (retention)
Secondary	Functional status (as measured by Functional Outcomes of Sleep Questionnaire)	Functional Outcomes of Sleep Questionnaire (FOSQ) encompasses 5 subscales: activity level, vigilance, intimacy and sexual relationships, general productivity, social outcome. An average score is calculated for each subscale and the 5 subscales are totaled to produce a total score. Subscale scores range from 1-4 with total scores ranging from 5-20. Higher scores indicate better functional status.	Baseline, 6-10 weeks (post-training), and 10-14 weeks (retention)
Secondary	Daytime sleepiness (as measured by Epworth Sleepiness Scale)	Scores on Epworth Sleepiness Scale range from range from 0 to 24, with higher scores indicating higher average sleep propensity in daily life (daytime sleepiness).	Baseline, 6-10 weeks (post-training), and 10-14 weeks (retention)
Secondary	Fatigue (as measured by Fatigue Severity Scale)	Fatigue Severity Scale measures the severity of fatigue and its effect on a person's activities and lifestyle. Scores range from 9 to 63, with higher scores indicating greater fatigue severity.	Baseline, 6-10 weeks (post-training), and 10-14 weeks (retention)
Secondary	Quality of Life (as measured by Stroke Impact Scale)	Stroke Impact Scale (SIS) assesses multidimensional stroke outcomes through 8 domains: strength (raw score range: 4-20), hand function (5-25), activities of daily living (score range 10-50), mobility (score range 9-45), communication (score range 7-35), emotion (score range 9-45), memory and thinking (score range: 7-35), and participation (8-40). Each domain is scored separately. For each domain, raw scores are transformed using the following formula: Transformed Scale = (Actual raw score - lowest possible raw score)*100 / (Possible raw score range). Higher scores indicate greater quality of life.	Baseline, 6-10 weeks (post-training), and 10-14 weeks (retention)
Secondary	Cognitive ability (as measured by Montreal Cognitive Assessment)	Montreal Cognitive Assessment (MoCA) is a screening test for detecting cognitive impairment. Scores range from 0 to 30, with higher scores indicating greater cognitive ability.	Baseline, 6-10 weeks (post-training), and 10-14 weeks (retention)