2006-11-09
CLINICAL STUDY PROTOCOL
STUDY IV
EFFECTS OF ORAL SCREEN TRAINING AND MANUAL
REGULATION THERAPY IN STROKE PATIENTS WITH
OROPHARYNGEAL DYSPHAGIA: A RANDOMISED TRIAL WITH
CONTROL GROUP
Study No.:
SIV-200611
Investigational Product:
The Oral Screen training device
Manual regulation therapy
Principal Investigator:
Mary Hägg, DDS
The clinical trial will be conducted, and essential study documentation archived,
in principle with UCR SOP’s and standards, which incorporate the
requirements of the ICH Guideline for Good Clinical Practice.
The following amendment(s) is/are accompanying the protocol:
1. Date:
UCR contact person (initials):
2. Date:
UCR contact person (initials):
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1. Signed agreement of the study protocol
Protocol number: SIV-200611
Title of the trial: Effects of oral screen training and manual regulation therapy in stroke
patients with oropharyngeal dysphagia: A randomised trial with
control group
We, the undersigned, have read and understood the protocol specified below and agree on the
contents.
Principle Investigator
Mary Hägg
Statistician
Lisa Wernroth
Data Manager
Patrik Holmqvist
2006-11-09
___________________________________
Signature
Date
___________________________________
Signature
Date
___________________________________
Signature
Date
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2. Table of Contents
1.
2.
3.
4.
5.
6.
Signed agreement of the study protocol ............................................................................. 2
Table of Contents ............................................................................................................... 3
List of abbreviations ........................................................................................................... 4
Investigators and study administrative structure ................................................................ 5
Background ........................................................................................................................ 6
Objectives and endpoints ................................................................................................... 6
6.1. Primary objective ....................................................................................................... 6
6.2. Primary endpoint ........................................................................................................ 6
6.3. Secondary objective ................................................................................................... 6
6.4. Secondary endpoint .................................................................................................... 6
7. Study design ....................................................................................................................... 7
7.1. Visit 0 (Screening; -3 week)....................................................................................... 8
7.2. Visit 1(Treatment start; week 0) ................................................................................. 8
7.3. Visit 2-5 (Treatment period) ...................................................................................... 9
7.4. Visit 6 (End of treatment)........................................................................................... 9
8. Study Treatment ................................................................................................................. 9
9. Study Population ................................................................................................................ 9
9.1. Inclusion criteria ......................................................................................................... 9
9.2. Exclusion criteria...................................................................................................... 10
9.3. Withdrawal Criteria .................................................................................................. 10
10.
Methods ........................................................................................................................ 10
10.1.
Swallowing Capacity Test .................................................................................... 10
10.2.
Lip Force Meter .................................................................................................... 10
10.3.
Meal Situation ...................................................................................................... 11
10.4.
Motility Function.................................................................................................. 11
10.5.
Sensory Function (oral stereognosia and two-point discrimination).................... 12
10.6.
Postural Scale for Stroke Patients (PASS) ........................................................... 12
10.7.
Velopharyngeal Closure Test ( VCT) .................................................................. 12
10.8.
Videofluoroscopy ................................................................................................. 12
10.9.
Subjective Evaluation ........................................................................................... 12
10.10. Body Mass Index (BMI) ...................................................................................... 13
10.11. EMG ..................................................................................................................... 13
10.12. PET ....................................................................................................................... 13
11.
Adverse events ............................................................................................................. 13
12.
Data Management ........................................................................................................ 13
13.
Statistical analysis ........................................................................................................ 14
13.1.
Determination of sample size ............................................................................... 14
13.2.
Primary analysis ................................................................................................... 14
13.3.
Secondary analysis ............................................................................................... 15
Supportive analysis of the primary variable ..................................................................... 15
Secondary endpoints ........................................................................................................ 16
14.
Informed consent .......................................................................................................... 16
15.
References .................................................................................................................... 17
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3. List of abbreviations
BMI
Body Mass Index
CI
Confidence Interval
CT
Conventional Therapy
CRF
Case Report Form
DMP
Data Management Plan
DVP
Data Validation Plan
DCF
Data Clarification Form
EMG
Electromyography
GCP
Good Clinical Practice
LFM
Lip Force Meter
MRT
Manual Regulation Therapy
ORT
Orofacial Regulation Therapy
OST
Oral Screen Training
PASS
Postural Assessment Scale for Stroke patients
PET
Positron Emission Tomography
SCT
Swallowing Capacity Test
SOP
Standard Operating Procedure
UCR
Uppsala Clinical Research Center. UCR is a clinical research consultant
organisation (CRO) at Uppsala University and University Hospital in
Uppsala.
VAS
Visual Analog Scale
VCT
Velopharyngeal Closure Test
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4. Investigators and study administrative structure
Principal Investigator:
Mary Hägg
Tal & Svälj Center, ÖNH
Hudiksvalls sjukhus, Hus 11
824 81 Hudiksvall
Sub Investigators:
Margaretha Olgarsson
Tal & Svälj Center, ÖNH
Hudiksvalls sjukhus, Hus 11
824 81 Hudiksvall
Bengt Larsson
Röntgen kliniken
Hudiksvalls sjukhus
824 81 Hudiksvall
Supervisor:
Matti Anniko
Öron-,näs- och halssjukdomar
Akademiska sjukhuset
SE-751 85 Uppsala
Data Manager:
Patrik Holmqvist
UCR
University Hospital
SE-751 85 Uppsala, Sweden
Statistician:
Lisa Wernroth
UCR
University Hospital
SE-751 85 Uppsala, Sweden
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5. Background
Orofacial Regulation Therapy (ORT) was introduced in 1990 and has often been clinically
applied to patients with oropharyngeal dysphagia in several hospitals around the world. ORT
comprises different ways to stimulate motor and sensory function, e.g. with the combination
of Manual Regulation Therapy (MRT) including the body and the orofacial region and
training with different oral devices. Since it is difficult to know which of the different
techniques that is most responsible for the therapeutic effect on oropharyngeal swallowing
disorders the aim is to study the effect of Oral Screen Training (OST) and MRT separately
and to compare the outcome with the effect of Conventional Therapy (CT). To this end stroke
patients will be randomised into three different groups, one that receives OST, one that is
assigned to MRT, and one CT, constitute the control group. All groups receive CT.
In order to avoid interference with spontaneous remission, patients in the three groups are
enrolled in the study one month after the stroke attack since mostly transient oropharyngeal
dysphagia is relieved within 2-3 weeks.
6. Objectives and endpoints
6.1.
Primary objective
The primary objective is to estimate the treatment effect of Manual Regulation
Therapy(MRT) and Oral Screen Training(OST) on swallowing capacity.
6.2.
Primary endpoint
The primary objective comprises two endpoints
 Change from start to end of treatment in Swallowing Capacity Test (SCT) result.
 Change from start to end of treatment in LFM result.
6.3.
Secondary objective
The secondary objective is to estimate the treatment effect of MRT and OST on functions
which are both dependent on and have an affect on swallowing capacity.
6.4.
Secondary endpoint
Changes from start to end of treatment in items divided into the following 11 categories
 Meal observation
 Oral motor performance
 Orofacial sensory function
 Gross motor skills
 PASS
 VCT
 Videofluoroscopy
 Patient self-assessment (VAS)
 BMI
 EMG
 PET
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7. Study design
The study will be conducted at the Speech and Swallowing Centre, ENT Department,
Hudiksvall Hospital.
The study design is a randomized parallel group design with three treatment arms.
Treatment 1: Manual Regulation Therapy
Treatment 2: Oral Screen Training
Treatment 3: Conventional Therapy = control group
Stroke patients with dysphagia at admission to a hospital will be referred to the speech and
swallowing centre for a screening visit during the first week. Their dysphagia will be assessed
with a SCT and a LFM at the screening visit on the stroke clinic (Visit 0) and at (Visit 1,
Week 0) 25 ± 4 days after the stroke incident on the Speech and Swallowing Centre. The
patients with persisting dysphagia, with a swallowing capacity lower than 10 ml/sec at Visit 1,
will be included and randomized into one of the three treatment arms and the total
investigation will be done. The treatment period, from week zero, will last for five weeks
followed by investigation as before treatment. The patients will visit the clinic at six
occasions, once a week, during six weeks.
Different investigations are performed before start of therapy and five weeks later after end of
therapy. Each week, all patients are in addition investigated with SCT and a LFM.
All patients in the different groups will receive CT, from the stroke onset until end of
treatment, comprising sitting and head position advices, adapted diet, and instructions in how
to stimulate the face and tongue with an electrical toothbrush and instructions in good oral
hygiene.
Six representative patients of the 66 (2 in each treatment group) will be selected to an EMG
and PET investigation (the same patients to the both investigation).
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Table 1. Trial schedule
Visit 0
-3 Week
Screening
Visit 1
Week 0
(Start of
Visit 2
Week 1
Visit 3
Week 2
Visit 4
Week 3
Visit 5
Week 4
Visit 6
Week 5
treat)
Demography
X
Date of stroke
X
Inclusion/Exclusion Criteria
X
Anamnesis
Social situation
Environment/General health/
VAS
Orofacial Journal:
Gross motor skills
PASS
X
X
X
X
X
X
X
X
X
X
X
X
X
Orofacial motor skills
Pharyngeal motility: Velum,
Mirror test
Sensory function
X
X
X
X
X
X
Intraoral examination
Saliva; normal-dry
Drooling
Bite force
X
X
X
X
X
X
X
Swallowing Capacity Test
X
X
X
X
X
X
X
Lip Force Meter
X
X
X
X
X
X
X
BMI/ADL/Diet
Meal observation
Videoradiography
X
X
EMG (6 patients)
PET (6 patients + 1 healthy)
7.1.
X
X
X
X
X
X
X
X
Visit 0 (Screening; -3 week)
At the stroke clinic, during the first week after the stroke incident, the dysphagia will be
assessed with a SCT and a LFM. A screening number will be given to the patient, identifying
him or her during the period between screening and start of treatment. All the patients are
treated conventionally.
7.2.
Visit 1(Treatment start; week 0)
At the Speech and Swallowing Centre 25 ± 4 days after the stroke incident the dysphagia will
be assessed with a SCT and a LFM. The patients with persisting dysphagia, will be given oral
and written information about the trial and will be asked to sign the informed consent form.
The investigator must keep a log identifying all patients having signed the informed consent
form. Afterward the patients will be included and randomized into one of the three treatment
arms. The total investigation will be done before the treatment start for respectively group
apart from the conventional therapy, which the patients continue with, and will last for five
weeks. Every patient has also to sign the treatment diary after each exercise.
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7.3.
Visit 2-5 (Treatment period)
Each week, patients in the two intervention groups and in the control group will visit the
clinic and are in addition investigated with SCT and a LFM.
7.4.
Visit 6 (End of treatment)
The treatment period, from week zero, will last for five weeks followed by investigation as
before treatment.
8. Study Treatment
All patients in the different groups will receive CT comprising sitting and head position
advices, adapted diet, and instructions in how to stimulate the face (buccinator mechanism,
the lips, the oral floor) and tongue with an electrical toothbrush three times daily and
instructions in good oral hygiene.
Patients in the OST group are instructed to train at home with the oral screen three times daily
before eating. The oral screen consists of a predental shield with a loop. For training, the
patient pulls at the loop while simultaneously trying to hold the screen with the lips. Each
exercise session consisted of pulling three times.
Patients assigned to MRT are treated once a week by a physiotherapist at the swallowing
centre. The body regulation is restricted to the shoulder-neck-head region. Its aim is to
achieve optimal head control, equilibrium of the infra-(n XII hypoglossus) and the
suprahyoidal muscles (n VII facialis, n V trigeminus, n XII hypoglossus) and to stimulate the
swallowing reflex. The orofacial regulation includes 14 different procedures.
9. Study Population
66 stroke patients with oropharyngeal dysphagia persisting for at least three weeks will be
included in the study.
Stroke patients with dysphagia at admission to a hospital will be referred to the speech and
swallowing centre at Hudiksvall Hospital for a screening visit. Their dysphagia will be
assessed with a SCT at the screening visit (Visit 0) and at Visit 1. The patients with persisting
dysphagia, represent a swallowing capacity lower than 10 ml/sec, at Visit 1, will be included
in the study.
9.1.

Inclusion criteria

Oropharyngeal dysphagia objectively (a swallowing capacity lower than 10 ml/sec)
persisting for 25±4 days
For the first time suffer from stroke including oropharyngeal dysphagia

Age 30-80 years

Consent by the subject to participate in the study
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9.2.

Exclusion criteria
Other neurological or psychiatric disease or other disease/injury that might affect the
swallowing function

Inability to cooperate

History of swallowing treatment

A prominent horizontal overbite

Hypersensitivity to acrylate, the oral screen
9.3.
Withdrawal Criteria
Patients are free to discontinue their participation in the study at any time. A patient’s
participation in the study might be discontinued at any time at the discretion of the
Investigator. Any patient’s participation in the study will be discontinued if any of the
following applies:





Consent withdrawn/The patient wishes to discontinue study treatment
Inability to cooperate
Best interest of patient, as judged by the investigator
Death
Other
10.
Methods
10.1.
Swallowing Capacity Test
The patient is asked to swallow 150 ml of cold tap water in one sweep and as quickly as
possible. The subject is instructed to sit upright, preferably on a chair at a table, then place the
glass close to the lower lip, and start drinking when the “go” signal is given (and stop
drinking in case of difficulties). The time is measured from the onset of drinking until the last
swallowing has been completed. Remaining water in the glass is measured. A swallowing
capacity index of 10ml/sec is regarded as the lower normal limit.
10.2.
Lip Force Meter
Lip Force Meter LF100 (LFM)
The Lip Force Meter (LF100, MHC1 AB Detector, Sweden) consists of a strain gauge applied
to the surface of an aluminium ring taking up the pulling force on the oral screen. The
detector is connected to an electronic unit for measuring maximal lip force. In order to obtain
the highest possible reproducibility of the measurement the pulling force has to be applied
perpendicular to the mouth of the patient. To this end a water-level has been attached to the
housing of the device.
The subjects are seated in a certified chair (REAL 9100 EL, Mercado Medic AB, Sweden)
with the body and the head in a strict upright position, with support for the feet, the knees in
straight angle position, and the hands resting in the lap. The investigator applies the force by
drawing the handle with increasing force backwards for a maximum of ten seconds or until
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the patient/subject loses grip of the screen. The maximum force value (newton) is observed by
an independent person. The investigator is blinded to this value.
Lip force is measured blindly 3 times by person A (MH) or by person B (MO) with a 2
minutes rest between measurements and the maximum force value is registered.
10.3.
Meal Situation
Each patient is served a meal consisting of 2 dl sour milk (youghurt that is liquid, but thicker
than ordinary milk), one slice of hard bread, and 1.5 dl of water. During the meal, the patient
is recorded with a video camera on video tape and simultaneously observed by one of the
authors (MH), who also filled in a questionnaire with the following parameters, each scored
from 0 (normal) to 4 (severe dysfunction): length of meal (1= >20 min, 2= >30 min, 3= >40
min, 4= inability to complete the meal); oral preparation time - from intake to initiation of
swallowing (1= sometimes > 10 sec, 2= often > 10 sec, 3= always > 10 sec, 4= complete
inability to swallow); drooling/oral leakage (1= sometimes, 2= often, 3= always, 4= complete
inability to keep saliva or food in the mouth); coughing when eating (1= sometimes, 2= often,
3= always); leakage to the nose (1= sometimes, 2= often, 3= always); and hoarseness (the
patients were asked how frequently they experienced hoarseness at meals, 1= sometimes, 2=
often, 3= always).
10.4.
Motility Function
The patients are placed in an upright and slightly forward position in a chair in front of a table
and are instructed to perform 29 different movements divided into five sections reflecting the
motor functions of head, facial muscles, lips, jaw, tongue and soft palate
The different items are scored (by the authors, M.H; M.O) from zero (normal) to 4 (severe
dysfunction) and registered in a test protocol. The motility tests are videotaped.
The movements relate to head control (6 variables): flexion, extension, rotation to the right
and left, lateral flexion to the right and left; facial expression, (4 variables), n VII facialis:
close the eyes tightly, make the eyes wide open and wrinkle the forehead, pull the brows close
together, wrinkle the nose; lips, (7 variables), n VII facialis : pout the lips, smile with closed
lips, smack as loud as possible, blow up the cheeks against pressure of a finger, suck the
cheeks together; repeat “oh-eeh” and “pah” three times as quickly and rhythmically as
possible (oral diadochokinesy): jaw,(5 variables, assessing the functions of the four chewing
muscles), n V trigeminus ; n mandibularis : open and close the mouth; move the lower jaw
forward, backward and to the left and right side: tongue, (8 variables), n XII hypoglossus:
stretch out the tongue as much as possible, move the tongue to the left and to the right corner
of the mouth, move the tongue three times alternatively to the right and to the left as quickly
and rhythmically as possible, point the tip of the tongue upwards and downwards, lick the lips
all around and the front side of the teeth in the upper and lower jaws three times; velum,
(1 variable), n X vagus, n V trigeminus, n VII facialis : say “ah” for evaluation of velum lift.
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10.5.
Sensory Function (oral stereognosia and twopoint discrimination)
The oral sensory function is examined through stereognostic tests. Eight metallic objects of
two different sizes (10 mm and 20 mm in diameter) and four different shapes (full circle, half
circle, star and triangle) are placed in the mouth of the patient, who is asked to match the
contour felt against a picture of five different objects. The time allowed for identification is at
the most 15 seconds. The objects are administered randomly and each one is presented twice.
Two-point discrimination is tested with a pair of compasses. The two points of the compasses
are placed with equal pressure on the epithelium until a slight indentation of the area is seen.
The space between the points differed depending on the area to be tested; the smallest
distinguishable distance in millimetres (the upper normal limit) are for the cheeks set to 15
mm, for the lips 5 mm, the tongue 3 mm and the anterior faucial arch 3 mm.
10.6.
Postural Scale for Stroke Patients (PASS)
PASS is a clinical scale for assessing stroke patients with respect to their capacity for postural
control. It comprises an assessment of the patient's capacity to retain or change his or her
posture while lying down, sitting down, or standing up. The ability to walk is not evaluated.
The assessment is easy to use clinically and takes only short time. The scale comprises twelve
activities judged according to a four degree scale (0-3), which gives a range from 0 to 36
points. The scale assesses performance for different postures and activities at varying levels of
difficulty.
The scale is primarily intended for new stroke patients but may also be used later in the
rehabilitation process. Studies have demonstrated good reliability and validity for PASS at
different phases after stroke. Tests of responsiveness have shown "fair to good levels",
especially for the first three months after the stroke.
10.7.
Velopharyngeal Closure Test ( VCT)
The ability to increase the intra-oral pressure is tested by instructing the patients to inhale
deeply and then exhale through a straw at a constant pace and for as long as they can against a
water pressure of 12 cm. The generally accepted lower normal limit is the ability to exhale
against a water pressure of 5 cm for at least 5 seconds.
10.8.
Videofluoroscopy
The following parameters are analysed by means of videofluoroscopy with low density
barium contrast medium: bolus control, oral retention, epiglottic closure, retention in
vallecula, retention in the pyriform sinus, aspiration (before, during, or after swallowing), and
cough with aspiration. All variables are given a score from zero (normal) to three (severe
dysfunction). Scoring is performed by a radiologist (one of the authors, B. L.) and intra-rater
reliability is tested several weeks later.
10.9.
Subjective Evaluation
The impact of dysphagia on their life situation are estimated by the patients on a 100 mm
VAS scale (0 = no impact, 100 = unbearable impact). Also a history is taken regarding the
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frequency of bronchopulmonary complications, hoarseness in connection with meals, the
patient’s mood and hobbies.
10.10.
BMI 
Body Mass Index (BMI)
weight (kg)
lenght 2 (m)
10.11.
EMG
See appendix 1.
10.12.
PET
See appendix 2.
11.
Adverse events
There will be slight risk or none at all for complications such as: aspiration during the SCT
when the patient is asked to swallow 150 ml water in one sweep. The patient will be informed
to stop drinking in case of difficulties or if we consider the test unworkable.
12.
Data Management
Data management will be performed by Clinical Data Management within the Biometric
section at UCR, in accordance with the Study specific Data Management Plan (DMP). Prior
to submitting the CRFs to data management for further processing, the investigators are
responsible for assuring that all data recorded within the CRF are legible, complete, correct,
and comply with the directives for recording data within the CRF.
CRF data will be singly entered into a Study database which will be subject to both logical
computerized checks and manual validation checks against listings, in accordance with the
Study specific Data Validation Plan (DVP). All inconsistencies detected during these
procedures will be resolved through Data Clarification Forms (DCF’s), being issued to the
investigational site personnel. A copy of the DCF will be filed with the CRF at the trial centre
and the original will be returned to UCR.
When all data entered into the database, including all coding, are deemed final a Clean File
procedure will be initiated including a Quality Control process preceding the actual Clean File
meeting, as specified within the DMP. Post clean file the database will be locked and the data
will be prepared for the statistical analysis and final export as specified within the DMP.
Data management and the data handling process will be conducted in accordance with Good
Clinical Practice (GCP), scientific and data management principles and in compliance with
UCR Standard Operating Procedures.
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13.
Statistical analysis
Statistical analysis will be conducted by a biostatistician at the Biometrics section at UCR. A
statistical analysis plan with a more detailed description of the analyses will be completed
before finalization of the study.
The main analysis will be performed on patients completing the study treatment period.
A patient flow diagram showing progress through the various stage of the study, including
flow of participants, withdrawals and deaths will be presented.
The significance tests will be two-sided and performed at 5% significance level.
Bootstrap will be used to calculate confidence interval for the median. The confidence
interval will be based on 10 000 bootstrap samples and the bias corrected method will be
applied.
13.1.
Determination of sample size
The primary variables are the changes from start to end of treatment in SCT result and in
LFM result. The sample size calculation is based on the assumption that data is normally
distributed. In order to retain an overall type I error of 5%, the type I error is set to 2.5% for
the two endpoints. Based on historical data, it is assumed that the standard deviation for the
change in SCT level is 3 ml/sec. To detect a critical difference of 2.8 ml/sec in SCT level
between treatment groups with a power of 80% and type I error of 2.5% a sample size of
approximately 20 subjects in each treatment group is required. The standard deviation for the
change in LFM is assumed to be approximately 5 N and to detect a critical difference of 4.2 N
the number of subjects will also be approximately 20.
Taking the possibility of drop-outs into account, a total of 22 subjects per treatment group is
needed, i.e. 66 in total.
13.2.
Primary analysis
The null hypothesis is that there are no differences in the change from Start to End of
treatment in SCT and LFM results among the three treatment groups. The alternative
hypothesis is that at least one group is different from the others regarding the endpoints.
The primary endpoints will be analysed with an analysis of covariance (ANCOVA) with the
SCT and LFM levels respectively as response variables, treatment-group as factor and the
level, at Start of treatment, of the response-variable as covariate. If the overall F-test indicate
no treatment effect, no further comparisons between the treatment groups will be made. The
95% CI for the mean differences, in change from baseline, among treatment groups will be
estimated from the ANCOVA model.
If the distribution of data is markedly non-normal the data will be transformed. If also the
distribution of the transformed data is non-normal a non-parametric method will be used. The
change from baseline to follow-up in SCT and LFM result will be calculated for each subject
and the Kruskal-Wallis test will be used to test if there is a significant difference between the
treatment groups.
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Permutation tests will be performed to ensure that the overall type I error will remain at 5 %
over the two primary endpoints. Individuals in the experiment are indexed from 1 to n. The
data are shuffled by computing a random permutation of the indices 1, …, n and assigning
the ith value of the endpoints to the individual whose index is given by the ith element of
permutation. The shuffled data are then analysed for effects. The resulting p-values at each
analysis point are stored and the entire procedure (shuffling and analysis) is repeated 10 000
times. A comparison wise critical value is obtained by ordering the minimum p-value over the
analysis of the two endpoints at each of the 10 000 analysis and finding their 5th percentile. If
the p-values obtained in the analyses of the primary endpoints are less than the critical value
obtained in the procedure above then the tests are considered to be statistically significant.
13.3.
Secondary analysis
The results from the secondary analyses of secondary endpoints will be regarded as
descriptive and hence no adjustment of the critical p-value will be performed.
All qualitative variables will be summarised in frequency tables for each treatment group and
visit respectively.
The quantitative variables will be summarised by number of observations, mean, standard
deviation, median, minimum and maximum values for each treatment group and visit
respectively.
Supportive analysis of the primary variable
95% two-sided CI for the average change will be calculated to estimate the swallowing
improvement for each treatment group .The CI will be estimated from the ANCOVA model.
If the distributions of data are markedly non-normal the data will be transformed.
If also the distribution of the transformed data is non-normal a 95% two-sided confidence
interval for the median change will be calculated to estimate the swallowing improvement for
each treatment group.
Boxplots and individual response profiles of SCT and LFM results for the seven visits will be
presented.
For each treatment group a 95% two-sided confidence interval, will be calculated for the
proportion of patients

with an improved SCT result (SCT at Start of treatment <SCT at End of treatment).

with a regained normal swallowing capacity (SCT>10 ml/s at End of treatment)

with an improved LFM result (LFM at Start of treatment <LFM at End of treatment).
Fisher’s exact test will also be calculated.
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Secondary endpoints
The median change from start to end of treatment will be calculated for Bite force, VCT,
VAS, BMI and PASS. A 95% two-sided confidence interval for the median change will be
presented.
95% two-sided confidence intervals for the proportion of patients with an improved result will
be calculated for each ordinal categorical response variable.
For each binomial response variable the proportion of patients with normal function at start
(ps ) and at end of treatment(pe) will be presented and a 95% confidence intervals for pe-ps
will be calculated (Table 2 and formula 1)
Table 2. Table of the result of a binomial response variable
Start of treatment
End of treatment Normal Dysfunction Total
Normal
A
B
a+b
Dysfunction
C
D
c+d
Total
a+c
b+d
n
pe  p s 
ab ac bc


(1)
n
n
n
Method 10 of Newcombe will be used to calculate the confidence interval for pe-ps
The mean severity score will be calculated for each of the six sections in the motility function
test. The change from start to end of treatment in mean severity will be calculated for each
subject (des) and a 95% two-sided confidence interval for the median change will be
calculated.
The mean severity score will be calculated for each of the seven sections in the
videofluoroscopy test. The change from start to end of treatment in mean severity will be
calculated for each subject (des) and a 95% two-sided confidence interval for the median
change will be calculated.
14.
Informed consent
The Investigator will ensure that each patient will be given full and adequate verbal and
written information about the nature, purpose, possible risk and benefit of the study. Patients
will also be notified that they are free to discontinue their participation in the study at any
time. The Investigator is responsible for obtaining consent from all patients before enrolment.
A suggested written patient information including the information on the liability in case of
injury and Informed Consent Form are provided in appendix 3.
Patients for whom consent could not be gathered will be placed on a waiting
list, reassessed daily, and included if they meet the entry criteria and consented within 21 days
of stroke onset.
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