Novel Management of Airway Protection in Parkinson's Disease: A Clinical Trial
Phase: PHASE2
Conditions: Parkinson's Disease, Dysphagia, Dystussia
Sponsor: Teachers College, Columbia University

Study Protocol and Sta.s.cal Analysis Plan 
 
Oﬃcial Title: Novel Management of Airway Protec5on in Parkinson's disease: A clinical trial 
 
NCT number: NCT02927691 
 
Document Date: (Grant submission – February 2016) 
 
Study Protocol 
This prospec5ve experimental study will include two par5cipant groups; one group will receive 
EMST and the other smTAP. Brieﬂy, once enrolled in the study, par5cipants will undergo baseline 
tes5ng consis5ng of airway protec5ve measures, physiological measures of respiratory and 
laryngeal func5on, and pa5ent-centered outcome measures. Par5cipants will then be randomly 
assigned with alloca5on concealment to either the EMST or smTAP training groups. They will be 
further randomized to receive immediate training or delayed training where there is a 5-week 
wait to start with a second baseline performed at the end of the 5-week delay. Whether 
par5cipants are in the immediate or delayed start groups, once treatment commences they will 
receive 5 weeks of intensive training including weekly mee5ngs with a trea5ng clinician in our 
clinical-research laboratory. Upon comple5on of the treatment arm, par5cipants will return for a 
post-treatment assessment consis5ng of all tests and measures from the ini5al baseline 
assessment. All treatment and assessment visits will be completed ‘on’ op5mal PD medica5on 
dosage which will be deﬁned as one hour a]er medica5on administra5on. Par5cipants may use 
diet and/or postural modiﬁca5ons as recommended by their trea5ng Speech-Language 
Pathologist to maintain nutri5onal status and swallowing safety during enrollment in the study, 
but are not to par5cipate in other dysphagia exercise-based rehabilita5on including treatments 
such as the eﬀoraul swallow, mendelsohn maneuver, etc. that have been shown to have exercise 
training eﬀects (e.g., [10]). Pre- and post-treatment procedures are described below. More 
speciﬁc informa5on about the selected outcomes is included in the ‘clinical protocol synopsis’. 
Pre and Post Treatment Assessments  
Swallowing Assessment Procedures. Three 10 cc thin liquid boluses by spoon and three 
3-oz thin liquid sequen5al swallow challenges will be administered by cup. Our research team has 
extensive experience in the evalua5on and measurement of swallowing dysfunc5on in PD (e.g., 
[20, 30, 31]).  A recent retrospec5ve analysis by our group of the swallowing performance of 50 
par5cipants with PD demonstrated that the 3-oz sequen5al swallow presenta5on was the best 
bolus presenta5on to detect change in swallowing performance. We will also include a smaller 
bolus (10 cc.) in the case that swallowing performance is so severe that it precludes the ethical 
presenta5on of the 3-oz liquid challenge.   
Reﬂex Cough Assessment Procedures. Par5cipants will be ouaiged with a facemask 
covering the nose and mouth. The facemask will be coupled to a pneumotachograph, diﬀeren5al 
pressure transducer, and have a side port with a one-way inspiratory valve for nebulizer 
connec5on. The nebulizer will be a DeVilbuss T-piece connected to a dosimeter that delivers 
aerosolized solu5on during inspira5on with a delivery dura5on of two seconds. The cough airﬂow 
signal will be digi5zed (Power Lab Data Acquisi5on System) and recorded (LabChart 7; 
ADInstruments, Inc) to a laptop computer.   

Par5cipants will be seated for an ini5al 30 seconds of quiet breathing in order to acclimate 
to the facemask. Par5cipants will then complete a capsaicin challenge with three randomized 
blocks of 0, 50, 100, 200, and 500 μM capsaicin dissolved in a vehicle solu5on. Our preliminary 
data iden5ﬁed 500 μM as a supra-threshold concentra5on for elici5ng the reﬂex cough in 
par5cipants with PD. Par5cipants will be given the instruc5on “cough if you need to” prior to 
capsaicin delivery. The solu5on will be administered automa5cally upon detec5on of an inspired 
breath and there will be a minimum of one minute between each trial. Par5cipants will be 
provided water to drink between trials. Our research group has extensive experience u5lizing this 
methodology to induce cough (e.g., [8, 22, 32, 33]).  Our group holds an FDA IND # 76866 for the 
use of capsaicin in the study of cough reﬂex sensi5vity and motor pagern.   
Treatment protocols:   
Every eﬀort was made to match the two targeted treatments on amount of 5me with clinicians, 
home prac5ce 5me, and number of repe55ons.   
Expiratory Muscle Strength Training (EMST) 
EMST involves a calibrated device consis5ng of a mouthpiece with a one-way spring-loaded valve. 
The valve blocks airﬂow un5l a suﬃcient "threshold" pressure is produced to overcome the force. 
The pressure range is from 25 cm H20 to 150 cm H20.  Par5cipants will receive training at baseline, 
have the device set to 75% of his/her MEP, and then complete EMST ﬁve days per week for ﬁve 
weeks. During that 5me period they will be seen for weekly study-treatment visits in our clinical-
research laboratory which will last approximately 45 minutes.    
Weekly study-treatment visits:  
During weekly visits, a study clinician will re-measure MEP, re-set the EMST device as 
appropriate (75% MEP), and observe the par5cipant complete the targeted 25 repe55ons. MEPs 
are completed by having the par5cipants blow into a mouthpiece connected to a pressure 
manometer via tubing with a 14-guage needle air-leak. The par5cipant blows into the manometer 
for two seconds.   
Home pracGce: 
 The daily training sessions will be completed at home, with the assistance of the par5cipant’s 
primary caregiver if necessary. Each day approximately 20-30 minutes will be spent training. The 
daily training is iden5cal to the protocol described above.   
Sensorimotor Training for Airway ProtecGon (smTAP)  
Par5cipants will complete 45 minutes of cough rehabilita5on in the laboratory with a trained 
research clinician once a week for ﬁve weeks. During the weekly visits, par5cipants will complete 
25 ‘hard/long coughs’ at sub-threshold levels of capsaicin.  Level of capsaicin will be determined 
from baseline (pre-test) measures. Par5cipants will train at the concentra5on just preceding their 
reﬂex cough threshold (C2). Agen5onal focus to the sub-threshold s5mulus will be emphasized. 
Visual feedback will be provided in real 5me via LabChart 7 (ADInstruments, Inc) and will be 
displayed on a large 20 inch desktop computer monitor. A visual target line 25% above maximum 
PEFR (derived from baseline cough assessment; ﬁgure 5) will be provided during cough training 
in order to promote enhanced PEFR. PEFR was selected as a primary target given that it has been 
iden5ﬁed as a measure which can be modiﬁed through cueing of reﬂex cough [22], is related to 
swallowing outcomes [34, 35], can be visually targeted by par5cipants, and is associated with 
increased cough eﬀec5veness. The par5cipants will only be provided with feedback regarding 

their performance on the ﬁrst ﬁve coughs trained within each session in order to reduce the 
inﬂuence of clinician bias on treatment outcomes.   
Home pracGce: The daily training sessions will be completed at home, with the assistance of the 
par5cipant’s primary caregiver if necessary. Each day approximately 20-30 minutes will be spent 
training.  Home prac5ce will be completed 5 out of 7 days. Par5cipants will complete 25 
voluntary coughs (5 sets of 5 repe55ons) using a peak ﬂow meter [36].  Each week the target 
peak cough ﬂow will be 25% above maximum PEFR as iden5ﬁed during the study treatment 
visits to the laboratory.   
 
Sta.s.cal Analyses 
Mul5level models with main eﬀects of treatment, 5me, and their two-way interac5on will be 
used. A randomeﬀect of par5cipant will be used to include mul5ple trials (eg, three trials of 
MEP at each 5me point). In the presence of an interac5on, diﬀerences in the magnitude of 
change between groups, as well as changes within each group, will be examined. For primary 
outcomes, separate models will be performed for delayed to pre-training and pre-training to 
post-training cohorts. More speciﬁcally, for par5cipants randomized to the delayed treatment 
group, MEP and voluntary cough PEFR will be tested between delayed (ﬁrst baseline) and pre-
training (second baseline). For the ac5ve treatment phase, all outcomes will be tested between 
pre-training (which was the second baseline for those in the delayed treatment group) and 
post-training. α will be set at 0.05, and mul5ple pairwise comparisons were adjusted via Holm–
Bonferroni correc5ons. Standardized eﬀect sizes will be computed by dividing mean diﬀerence 
by the error and random eﬀect variance. Single measure, absolute agreement intraclass 
correla5on coeﬃcients and weighted Cohen’s kappa will be used for cough airﬂow and number 
of coughs, respec5vely, for reliability. Analyses will be performed in R.