Comment Period Extended to 3/23/2015 for Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

Cough and Swallow Rehab Following Stroke

This study is currently recruiting participants. (see Contacts and Locations)
Verified February 2015 by University of Florida
American Heart Association
Information provided by (Responsible Party):
University of Florida Identifier:
First received: July 11, 2013
Last updated: February 4, 2015
Last verified: February 2015

July 11, 2013
February 4, 2015
January 2011
December 2015   (final data collection date for primary outcome measure)
Maximum Expiratory Pressure [ Time Frame: Change in baseline to week 7 ] [ Designated as safety issue: No ]
This measure will indicate if there are strength gains in the respiratory muscle by measuring expiratory pressure generating ability.
Same as current
Complete list of historical versions of study NCT01907321 on Archive Site
Cough expiratory airflow [ Time Frame: Change in baseline to 7 weeks ] [ Designated as safety issue: No ]
Cough airflow measure of peak expiratory flow rate
Same as current
Not Provided
Not Provided
Cough and Swallow Rehab Following Stroke
Cough and Swallow Rehabilitation Following Stroke

Stroke is the leading case of neurologic swallow dysfunction, or dysphagia. Post stroke dysphagia is associated with approximately 50% increase in the rate of pneumonia diagnoses; aspiration pneumonia is the most common respiratory complication in all stroke deaths, accounting for a three-fold increase in the 30-day post stroke death rate. The long-term goal of this systematic line of research is to decrease the morbidity, mortality, and health care costs associated with disordered airway protection following stroke.

The overall hypothesis central to this proposal is that the ability to protect the airway is dependent upon a continuum of multiple behaviors, including swallowing and cough. Safe, efficient swallowing prevents material from entering the larynx and lower airway, and effective cough ejects aspirate or mucus material. Currently, only one end of the continuum, swallowing, is rigorously assessed in stroke patients. However, ineffective or disordered cough is indicative of the inability to eject aspirate material or clear mucus and secretions from the lower airway. Ineffective clearance and subsequent accumulation of material in the lower airway increases the risk of chest infection. Hence, patients at the greatest risk for chest infection would not only have disordered swallowing (dysphagia) but also disordered cough (dystussia), meaning they are more likely to aspirate material and then cannot effectively eject the aspirate from the airway. There is a high likelihood that swallowing and cough are simultaneously disordered following stroke. To date, there is a treatment that targets both swallowing and cough function in stroke patients.

Expiratory muscle strength training (EMST) increases expiratory muscle strength (Baker et al., 2005) and there is evidence that supports its use to improve both swallow and cough functions in patients with Parkinson's disease (Troche et al., in press). This cross-system, device-driven approach to rehabilitating multiple contributors to airway protection deficits is highly desirable in the stroke population due to the likelihood of the co-occurrence of both swallow and cough disorders. To date, EMST has not been tested in stroke patients. We propose that by including cough in the screening, evaluation and treatment processes for disorders of airway protection, we will be able to better identify and treat patients most at risk for airway compromise and associated sequelae.

Research Design and Methods This pilot study will include twenty acute (1-14 days post-ictus) and subacute (14 days - 6 months post-ictus) ischemic stroke patients between the ages of 50 and 80 as participants. Once enrolled, participants will complete a battery of pre-training baseline measures ('measures' subheading below) and then be randomized to one of two groups: the experimental EMST group, or the control group. The training (EMST group) or control period will last for 5 weeks, and there will then be a post-training assessment that will consist of the same measures that were taken during the initial baseline visit.

Once informed consent is obtained, medical records will be reviewed for confirmation that the patient meets inclusion and exclusion criteria. Cognitive status: Cognitive status in stroke brain injured patients is known to impact recovery and relate to dysphagia, risk of aspiration, and cough. We will use the National Institutes of Health Stroke Scale (NIHSS) assess stroke severity (Appendix 1). The NIHSS will be treated as an independent predictor of cough and/or swallow dysfunction.


Maximum Expiratory Pressure: Maximum expiratory (MEP) pressures are an indirect measure of expiratory muscle strength. The measurement apparatus consists of a mouthpiece connected to a pressure manometer by 50 cm of 2 mm i.d. tubing with a 14-gauge-needle air-leak. In order to measure MEP, the participant will be seated with the nose occluded with nose clips. After inhaling to total lung capacity, the participant will place his or her lips around the mouthpiece and blow out as forcefully as possible. Repeated measures will be taken with a one to two minute rest between trials, until three measurements obtained are within 5%. The average of these three values will be recorded.

Lung function test: Forced Vital Capacity (FVC) and Force Expiratory Volume at one second (FEV1): The participants will be asked to breathe in to their total lung capacity. The participants will then be asked to blow out as forcefully as possible into a computerized spirometer. FEV1 is a measure of expiratory volume during the first second of expiration during the forced vital capacity maneuver. Alternatively, if the subject is unable to perform the cognitive voluntary spirometric task, upper airway respiratory resistance (R5) will be measured with impulse oscillometry (IOS, Jaeger Instruments). Impulse oscillometry requires the participant to breath through a mouthpiece connected to the computer. The mouthpiece apparatus delivers small puffs of air whose reverberations provide measures of upper and lower airway resistance. This takes approximately 5-10 minutes to complete.

Cough: Participants will be instrumented for the measurement of the respiratory airflow pattern during spontaneous breathing, voluntary cough and capsaicin induced reflex cough. A facemask connected to a pneumotachograph will be used to record the airflow and expiratory muscle activity will be measured with surface electromyography (sEMG), with electrodes placed over the rectus abdominus muscle, and over the 8th intercostal space. The mouth airflow signal and sEMG signal will be digitized and recorded on a desktop computer (Chart, ADInstruments, Inc). The computer signals will be analyzed to determine timing and duration of the inspiratory, expiratory and compression phases, as well as the peak and mean expiratory airflow of each cough (Figure 4), and associated sEMG amplitude measures. Because it has been recently reported that acute stroke related brain injury differentially affects the motor pattern of voluntary and reflex elicited coughs (Ward et al., 2010), hence it is essential to elicit coughs with both peripheral afferent stimulation (capsaicin; 'reflexive' cough) and voluntary induced cough.

Voluntary cough: Participants will be seated with a facemask connected to a pneumotachograph. They will be instructed to produce a strong cough three times into the facemask. They will rest for one minute between trials. This will take 5 - 10 minutes to complete.

Reflexive cough / capsaicin administration: After the participant is instrumented with facemask, he/she will be seated comfortably in a chair in front of an airflow fume hood. The airflow fume hood prevents exposure of the participant and experimenter to the nebulized solution except when the participant inhales for the capsaicin challenge. Participants will inspire deeply through the nebulizer (containing the capsaicin or a vehicle solution) coupled to the facemask and pneumotachograph. The outflow nebulizer gas will be passed through an isopropyl alcohol solution to remove capsaicin from the air vented into the fume hood. Dr. Davenport holds an FDA IND # 76866 for the use of capsaicin in the study of cough motor pattern. This will take 10 minutes to complete.

Swallowing Evaluation: Videofluoroscopic measures: Swallowing will be assessed using a high resolution, dual modality videofluoroscopic (VFS) recording device with signal acquisition (digitized at 250 Hz) and digital storage and retrieval of respiratory and swallowing data (Digital Swallowing Workstation, model 7100, Lincoln Park, NJ: Kay Elemetrics). The clinical swallow examination comprises: a brief swallowing history, an oral motor examination, a 3 oz swallowing test, and a Videofluoroscopic Swallowing Examination (VFSE). The oral motor examination assesses the strength, timing and tone of jaw, lips, face, larynx and velopharynx as these structures all contribute to safe, adequate swallowing. Their impairment is predictive of swallowing abnormality. The 3 oz swallow test, requires each person to swallow three ounces of water. It is also strongly associated with aspiration on instrumental testing. The VFSE includes videotaping the participant in the radiologic suite (Shands radiology department) using standard fluoroscopic systems with remote monitor and a standard lateral view of the oropharynx. This lateral view will allow visualization of all critical oral and pharyngeal structures, including jaw, lips, tongue, soft palate, larynx and pharynx. A video counter will imprint a time code on each examination to aid subsequent analysis. Each examination will consist of 6, 5-ml and 10-ml thin liquid swallows, 3, 15-ml thin liquid swallows, 6, 5-ml and 10-ml swallows of barium pudding, and one, 3oz thin liquid. Standardized "bail-out" criteria will be used to eliminate serious aspiration.

The Modified Barium Swallow Impairment Profile (MBSImp™) will be used to analyze the VFS recordings and determine the presence of oral and/or pharyngeal swallowing impairment. The MBSImp is a validated tool (B. Martin-Harris et al., 2008) for assessing swallow impairment. Six objective components of oral and pharyngeal impairment are included on the scoring form, thus giving an overall impression of swallowing performance.

The penetration-aspiration scale (PAS) (Rosenbek, Robbins, Roecker, Coyle, & Wood, 1996) will be used to assess penetration or aspiration; the PAS is an 8-point scale that ranges from 1 (no penetration/aspiration) to 8 (aspiration with no cough response).

EMST training procedures As indicated in the Informed Consent Form, after completion of the baseline testing, participants will be randomized to either an experimental EMST group, or a control group. Participants in both groups will follow any compensatory strategies, including diet modifications and/or postural adjustments recommended for safe swallowing based on the initial swallowing examination. In addition, the EMST group will receive 5 weeks of EMST.

  1. The EMST group will be given an expiratory pressure threshold trainer, which consists of plexiglass tube with a variable tension spring controlling a "pop-off" valve. The threshold training device used in this study will be a modification of a commercially available device manufactured by HealthScan, Inc. The modification of this device allows the pressure threshold to be set up to 160 cmH20. The current device only allows pressure threshold settings up to 20 cmH20. The higher pressure-threshold settings are necessary to allow the threshold to be set at 75% of the participant's MEP.
  2. The training protocol will consist of five sets of five breaths, five days per week for 5 weeks with the pressure threshold set at 75% of the participant's most recently acquired MEP. The EMST participants will be provided with written (Appendix 2) and verbal instructions for the completion of the training protocol. Participants will mark the completion of training sets on a log sheet (Appendix 3) each week.
  3. Each EMST participant will be visited at their home by a trained therapist once a week during each week of the 5 week training period. The participant's MEP will be measured at this time. Three trials will be completed. The maximum value will be used in the dataset. Any participant concerns regarding the training program will be addressed at this time.
  4. Following the training period, all of the baseline measures described above for breathing, coughing, and swallowing will be re-evaluated. This will constitute the post-training baseline measures and will occur within one following the 5-week intervention

Control group procedures:

As indicated in the Informed Consent Form, after completion of the baseline testing, participants will be randomized to either an experimental EMST group, or a control group. Participants randomized to the control group will not be involved in any EMST treatment paradigm or any other exercise treatment paradigm, but as with the EMST group, participants may be using compensatory strategies as per standard of care. This will ensure they are able to safely maintain adequate nutritional status. Participants in this group will be assessed at the pre-training and post-training visits using the identical protocol for that of the EMST group. They will not receive weekly home visits.

Phase 1
Phase 2
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Subject)
Primary Purpose: Treatment
Ischemic Stroke
  • Behavioral: Expiratory muscle strength training
    Small hand held device that provides calibrated (cmH20) resistance to expiratory pressure. Once sufficient pressure is achieved (participant blowing out into the device) a valve is released, letting air flow through.
    Other Name: EMST
  • Behavioral: Placebo expiratory training
    Device with the same look and feel as the active EMST, but which provides no resistance to airflow.
  • Drug: Measures perfomed on all subjects
    Capsaicin is a cough-inducing vapor that will be inhaled by participants to induce coughing. The airflow of the cough will be recorded and measures of compression phase duration, peak expiratory flow rate, and post-peak plateau phase will be made.
    Other Name: Capsaicin
  • Behavioral: Pulmonary function test
    Measures of forced vital capacity (FVC) and Forced expiratory volume in the 1st second (FEV1), and the ratio between the two measures (FEV1/FVC). Also included is the measure of maximum expiratory pressure. Airflow from the voluntary cough will also be recorded and measured using the spirometric system. These measures will be identical to those made on the capsaicin-induced cough.
    Other Name: Spirometry
  • Radiation: Fluoroscopic swallow study
    Images from the swallow study will be used to determine the modified barium swallow impairment profile (MBSImp) score, as well as the penetration-aspiration score (PA).
    Other Name: Modified barium swallow study
  • Experimental: Expiratory muscle strength training (EMST)
    Participants will complete 5 weeks of EMST training, 5 repetitions per set, 5 sets per day, 5 days per week.
    • Behavioral: Expiratory muscle strength training
    • Drug: Measures perfomed on all subjects
    • Behavioral: Pulmonary function test
    • Radiation: Fluoroscopic swallow study
  • Placebo Comparator: Placebo expiratory training
    Same look and feel of EMST with no resistance. Same protocol - 5 repetitions of 5 sets, 5 days per week
    • Behavioral: Placebo expiratory training
    • Drug: Measures perfomed on all subjects
    • Behavioral: Pulmonary function test
    • Radiation: Fluoroscopic swallow study
Not Provided

*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
December 2015
December 2015   (final data collection date for primary outcome measure)

Inclusion Criteria:

  1. Acute (0-14 days) and subacute (14 days - 6 months) ischemic stroke
  2. Neurologic status permits participation.
  3. Medical status permits participation.

Exclusion Criteria:

  1. Dysphagia secondary to something other than stroke.
  2. Refuses consent.
  3. Incapable of informed consent and has no representative.
  4. Multiple strokes and previous history of dysphagia secondary to stroke.
  5. Longer than 6 months post-stroke
  6. Known cardiac valve thrombosis
  7. Stroke etiology of dissection
  8. Unstable / evolving stroke lesion.
  9. History of cancer in the head or neck
  10. History of radiation to the head or neck
  11. History of degenerative disease
50 Years to 85 Years
Contact: Karen W Hegland, PhD 352 373-3710
United States
University of Florida
University of Florida
American Heart Association
Principal Investigator: Karen W Hegland, PHD University of Florida
University of Florida
February 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP