Expiratory Muscle Strength Training (EMST) in Neuromuscular Disorders

Muscular Dystrophies Clinical Trial

Official title:

Interventional Study of Expiratory Muscle Strength Training as a Treatment in Neuromuscular Disorders

Clinical Trial Details — Status: Enrolling by invitation

Administrative data

• NCT number: NCT04009408
• Other study ID #: REB18-1121
• Status: Enrolling by invitation
• Phase: N/A
• Start date: May 2022
• Est. completion date: December 1, 2022

Study information

• Verified date: April 2022
• Source: University of Calgary
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to investigate the impact of expiratory muscle strength training (EMST) on the swallowing, breathing, oral intake, quality of life and cough function of people with oculopharyngeal muscular dystrophy (OPMD).

Description:

Outline:

Twenty participants with OPMD, with dysphagia, will be recruited from Neuromuscular clinics within Calgary. The investigators will enrol patients in a parallel group, sham-controlled, randomized clinical trial, with 10 participants in each group (active EMST and sham EMST).

Participants will have baseline measurements of: (i) global swallowing function via modified barium swallow study, (ii) maximum expiratory pressure, (iii) voluntary cough spirometry, (iv) forced vital capacity, (v) functional oral intake, (vi) patient report of self-perceived swallowing impairment (EAT-10 Questionnaire), and (vii) biomarker analyses.

Participants will undergo 5-weeks of EMST (active or sham). All baseline measurements will be repeated after 5-weeks of EMST and 10-weeks post-EMST to measure durability of effect.

Outcomes:

The end-goal of the current research is to obtain preliminary data for the benefit of EMST in a new study population, and direct future studies that may provide evidence for a new standard of care in treating neuromuscular diagnoses.

Recruitment information / eligibility

• Status: Enrolling by invitation
• Enrollment: 20
• Est. completion date: December 1, 2022
• Est. primary completion date: December 1, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Diagnosis of oculopharyngeal muscular dystrophy (OPMD)

• 18 years of age or older

• Must be capable of providing informed consent

• Must be able to undergo respiratory function testing and swallowing studies

• Must have a forced vital capacity (FVC) greater than 60%

• A score of 3 or greater on the Eating Assessment Tool-10 (EAT-10; self-administered, symptom-specific outcome instrument for dysphagia. A score of 3 or greater indicates increased stress around eating)

• A score of 26 or greater on the Montreal Cognitive Assessment (MoCA; 30-point screening assessment used for detecting cognitive impairment. A score of 26 or greater is considered to be within functional limits.)

Exclusion Criteria:

• Severe coronary artery disease

• Acute myocardial infarction

• Moderate to severe hypovolemia

• Acute neurological events

• Unstable cardiac status

• Recent hernia

• Severe chronic obstructive pulmonary disease (COPD)

• Uncontrolled reflux issues

• Women who are pregnant, or who suspect they may be pregnant

• Cognitive impairment that would prevent comprehension of instructions and adherence to intervention guidelines (a score of less than 26 points on the MoCA)

Related Conditions & MeSH terms

• Muscular Diseases
• Muscular Dystrophies
• Muscular Dystrophy, Oculopharyngeal
• Myopathy; Hereditary
• Neuromuscular Diseases
• Oculopharyngeal Muscular Dystrophy

Intervention

Device:
• Expiratory muscle strength therapy (EMST150, Aspire LLC)
Active therapy calibrated to the participant's maximum expiratory pressure

Locations

Country	Name	City	State
Canada	Neuromuscular Clinic, South Health Campus	Calgary	Alberta

Sponsors (2)

Lead Sponsor	Collaborator
University of Calgary	Muscular Dystrophy Canada

Country where clinical trial is conducted

Canada, 

References & Publications (23)

Abu-Baker A, Rouleau GA. Oculopharyngeal muscular dystrophy: recent advances in the understanding of the molecular pathogenic mechanisms and treatment strategies. Biochim Biophys Acta. 2007 Feb;1772(2):173-85. Epub 2006 Oct 11. Review. — View Citation

Belafsky PC, Mouadeb DA, Rees CJ, Pryor JC, Postma GN, Allen J, Leonard RJ. Validity and reliability of the Eating Assessment Tool (EAT-10). Ann Otol Rhinol Laryngol. 2008 Dec;117(12):919-24. — View Citation

Chiara T, Martin AD, Davenport PW, Bolser DC. Expiratory muscle strength training in persons with multiple sclerosis having mild to moderate disability: effect on maximal expiratory pressure, pulmonary function, and maximal voluntary cough. Arch Phys Med Rehabil. 2006 Apr;87(4):468-73. — View Citation

Chiò A, Logroscino G, Hardiman O, Swingler R, Mitchell D, Beghi E, Traynor BG; Eurals Consortium. Prognostic factors in ALS: A critical review. Amyotroph Lateral Scler. 2009 Oct-Dec;10(5-6):310-23. doi: 10.3109/17482960802566824. Review. — View Citation

Crary MA, Mann GD, Groher ME. Initial psychometric assessment of a functional oral intake scale for dysphagia in stroke patients. Arch Phys Med Rehabil. 2005 Aug;86(8):1516-20. — View Citation

Duranceau CA, Letendre J, Clermont RJ, Lévesque HP, Barbeau A. Oropharyngeal dysphagia in patients with oculopharyngeal muscular dystrophy. Can J Surg. 1978 Jul;21(4):326-9. — View Citation

Ertekin C, Yüceyar N, Aydogdu, Karasoy H. Electrophysiological evaluation of oropharyngeal swallowing in myotonic dystrophy. J Neurol Neurosurg Psychiatry. 2001 Mar;70(3):363-71. — View Citation

Hutcheson KA, Barrow MP, Barringer DA, Knott JK, Lin HY, Weber RS, Fuller CD, Lai SY, Alvarez CP, Raut J, Lazarus CL, May A, Patterson J, Roe JW, Starmer HM, Lewin JS. Dynamic Imaging Grade of Swallowing Toxicity (DIGEST): Scale development and validation. Cancer. 2017 Jan 1;123(1):62-70. doi: 10.1002/cncr.30283. Epub 2016 Aug 26. — View Citation

Jones HN, Crisp KD, Robey RR, Case LE, Kravitz RM, Kishnani PS. Respiratory muscle training (RMT) in late-onset Pompe disease (LOPD): Effects of training and detraining. Mol Genet Metab. 2016 Feb;117(2):120-8. doi: 10.1016/j.ymgme.2015.09.003. Epub 2015 Sep 8. — View Citation

Luchesi KF, Kitamua S, Mourão LF. Amyotrophic Lateral Sclerosis survival analysis: Swallowing and non-oral feeding. NeuroRehabilitation. 2014;35(3):535-42. doi: 10.3233/NRE-141149. — View Citation

Nimmons D, Pendleton N, Payton A, Ollier W, Horan M, Wilkinson J, Hamdy S. A novel association between COMT and BDNF gene polymorphisms and likelihood of symptomatic dysphagia in older people. Neurogastroenterol Motil. 2015 Sep;27(9):1223-31. doi: 10.1111/nmo.12609. Epub 2015 Jun 14. — View Citation

Paris G, Martinaud O, Petit A, Cuvelier A, Hannequin D, Roppeneck P, Verin E. Oropharyngeal dysphagia in amyotrophic lateral sclerosis alters quality of life. J Oral Rehabil. 2013 Mar;40(3):199-204. doi: 10.1111/joor.12019. Epub 2012 Dec 27. — View Citation

Pitts T, Bolser D, Rosenbek J, Troche M, Okun MS, Sapienza C. Impact of expiratory muscle strength training on voluntary cough and swallow function in Parkinson disease. Chest. 2009 May;135(5):1301-1308. doi: 10.1378/chest.08-1389. Epub 2008 Nov 24. — View Citation

Plowman EK, Tabor LC, Robison R, Gaziano J, Dion C, Watts SA, Vu T, Gooch C. Discriminant ability of the Eating Assessment Tool-10 to detect aspiration in individuals with amyotrophic lateral sclerosis. Neurogastroenterol Motil. 2016 Jan;28(1):85-90. doi: 10.1111/nmo.12700. Epub 2015 Oct 28. — View Citation

Plowman EK, Tabor-Gray L, Rosado KM, Vasilopoulos T, Robison R, Chapin JL, Gaziano J, Vu T, Gooch C. Impact of expiratory strength training in amyotrophic lateral sclerosis: Results of a randomized, sham-controlled trial. Muscle Nerve. 2019 Jan;59(1):40-46. doi: 10.1002/mus.26292. Epub 2018 Nov 29. — View Citation

Plowman EK, Watts SA, Tabor L, Robison R, Gaziano J, Domer AS, Richter J, Vu T, Gooch C. Impact of expiratory strength training in amyotrophic lateral sclerosis. Muscle Nerve. 2016 Jun;54(1):48-53. doi: 10.1002/mus.24990. Epub 2016 Mar 3. — View Citation

Raginis-Zborowska A, Pendleton N, Hamdy S. Genetic determinants of swallowing impairment, recovery and responsiveness to treatment. Curr Phys Med Rehabil Rep. 2016;4(4):249-256. doi: 10.1007/s40141-016-0133-6. Epub 2016 Aug 8. Review. — View Citation

Robison R, Tabor-Gray LC, Wymer JP, Plowman EK. Combined respiratory training in an individual with C9orf72 amyotrophic lateral sclerosis. Ann Clin Transl Neurol. 2018 Aug 21;5(9):1134-1138. doi: 10.1002/acn3.623. eCollection 2018 Sep. — View Citation

Rosenbek JC, Robbins JA, Roecker EB, Coyle JL, Wood JL. A penetration-aspiration scale. Dysphagia. 1996 Spring;11(2):93-8. — View Citation

Silverman EP, Miller S, Zhang Y, Hoffman-Ruddy B, Yeager J, Daly JJ. Effects of expiratory muscle strength training on maximal respiratory pressure and swallow-related quality of life in individuals with multiple sclerosis. Mult Scler J Exp Transl Clin. 2017 May 29;3(2):2055217317710829. doi: 10.1177/2055217317710829. eCollection 2017 Apr-Jun. — View Citation

Tabor LC, Rosado KM, Robison R, Hegland K, Humbert IA, Plowman EK. Respiratory training in an individual with amyotrophic lateral sclerosis. Ann Clin Transl Neurol. 2016 Sep 1;3(10):819-823. eCollection 2016 Oct. — View Citation

Troche MS, Okun MS, Rosenbek JC, Musson N, Fernandez HH, Rodriguez R, Romrell J, Pitts T, Wheeler-Hegland KM, Sapienza CM. Aspiration and swallowing in Parkinson disease and rehabilitation with EMST: a randomized trial. Neurology. 2010 Nov 23;75(21):1912-9. doi: 10.1212/WNL.0b013e3181fef115. — View Citation

Yang R, Huang R, Chen D, Song W, Zeng Y, Zhao B, Zhou D, Shang HF. Causes and places of death of patients with amyotrophic lateral sclerosis in south-west China. Amyotroph Lateral Scler. 2011 May;12(3):206-9. doi: 10.3109/17482968.2011.572979. Epub 2011 Apr 21. — View Citation

* Note: There are 23 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Global Swallowing Function	Global swallowing function is rated from videofluoroscopy swallowing studies (VFSS), using the Dynamic Imaging Grade of Swallowing Toxicity (DIGEST), a validated 5-point scale. Global swallowing function is rated from 0-4: 0 = no pharyngeal dysphagia; 1 = mild; 2 = moderate; 3 = severe; 4 = life-threatening. A lower score is a better outcome.	Change in score from week 0 to week 5
Secondary	Global Swallowing Function	Global swallowing function is rated from videofluoroscopy swallowing studies (VFSS), using the Dynamic Imaging Grade of Swallowing Toxicity (DIGEST), a validated 5-point scale. Global swallowing function is rated from 0-4: 0 = no pharyngeal dysphagia; 1 = mild; 2 = moderate; 3 = severe; 4 = life-threatening.	Change in score from week 0 to week 15; change in score from week 5 to week 15.
Secondary	Maximum expiratory pressure (MEP)	MEP is a measure of respiratory muscle strength and is assessed with a handheld manometer, measured in centimetres of water (cmH2O). A higher score is a better outcome.	Change in score from week 0 to week 5; change in score from week 0 to week 15; change in score from week 5 to week 15.
Secondary	Volitional cough strength (peak cough flow)	Measure of cough strength that is assessed using a spirometer, measured in litres per minute (L/min). A higher score is a better outcome.	Change in score from week 0 to week 5; change in score from week 0 to week 15; change in score from week 5 to week 15.
Secondary	Forced vital capacity (FVC)	Measure of how much air is exhaled during forced exhalation and is assessed with a spirometer, measured in litres. A higher score is a better outcome.	Change in score from week 0 to week 5; change in score from week 0 to week 15; change in score from week 5 to week 15.
Secondary	Oral Intake	A measure daily nutritional and hydration consumption. Oral intake is assessed using the Functional Oral Intake Scale (FOIS), a validated 7-point ordinal scale (1 = no oral intake; 2 = tube dependent with minimal/inconsistent oral intake; 3 = tube supplements with consistent oral intake; 4 = total oral intake in single consistency; 5 = total oral intake of multiple consistencies requiring special preparation; 6 = total oral intake with no special preparation, but must avoid specific foods or liquid items; 7 = total oral intake with no restrictions). A higher score is a better outcome.	Change in score from week 0 to week 5; change in score from week 0 to week 15; change in score from week 5 to week 15.
Secondary	Self-perceived swallowing impairment	Will be measured using the Eating Assessment Tool-10 (EAT-10), a self-administered, symptom-specific outcome instrument for dysphagia. The EAT-10 allows patients to rate their swallowing symptoms on scale of 0 = no problem to 4 = severe problem. A lower score is a better outcome.	Change in score from week 0 to week 5; change in score from week 0 to week 15; change in score from week 5 to week 15.
Secondary	Biomarker analyses	An optional blood sample will be collected for biomarker analysis, to identify correlations with clinical response. We will measure genetic biomarkers associated with swallowing function including rs6265, rs165599, rs10835211, rs17601696, and APOE4 genotype status. For these 5 genetic biomarkers, participants will be scored as having zero, one, or two alleles. This information will be used in subgroup analyses for the primary and secondary outcomes.	Baseline measurement (week 0)