Motor Performance Modulation After Total Knee Replacement
Conditions: Total Knee Replacement
Sponsor: Istituto Clinico Humanitas

 
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Motor performance modulation after total knee 
replacement 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
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PROTOCOL NAME: Motor performance modulation after total knee 
replacement. 
 
 
PROTOCOL IDENTIFYING NUMBER: CLF18/06 
 
 
PROTOCOL VERSION DATE: 07-11-2018 
 
 
 
 
 
Contact addresses:                                                  roberto.gatti@hunimed.eu 
 
 
 
 
Study coordinator: 
Roberto Gatti 
+390282245610  
 
 
 
 
 
 
 
 
 
 
 

 
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Glossary of abbreviations 
 
 
TKR: Total Knee Replacement  
AMI: Arthrogenic Muscle Inibition  
STS: Sit To Stand 
10MWT: 10 Metres Walking Test 
MdF: Torque  
RoM: Range of Motion 
OS: Overshoot 
FRE: Force Reproduction Error 
ICH: Istituto Clinico Humanitas 
KOOS: Knee Injury and Osteoarthritis outcome score 
IPAQ: International Physical Activity Questionnaire 
  
 
 
 
 
 
 
 

 
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INDEX 
 
1- SYNOPSIS…………...………………………………………………………………........ 
2- BACKGROUND AND INTRODUCTION ..................................................................... 
3- STUDY’S RATIONALE.................................................................................................... 
4- STUDY’S OBJECTIVES .................................................................................................. 
4.1 general objectives ......................................................................................................... 
4.2 End-points .................................................................................................................... 
4.2.1 Primary endpoint ................................................................................................ 
4.2.2 Secondary endpoint............................................................................................. 
5- SELECTION CRITERIA ................................................................................................. 
5.1 Inclusion criteria .......................................................................................................... 
5.2 Exclusion criteria ......................................................................................................... 
6- STUDY DESIGN ............................................................................................................... 
6.1 General Design ............................................................................................................. 
7- STATISTICAL CONSIDERATIONS ............................................................................. 
7.1 Sample size ................................................................................................................... 
7.2 Analysis ......................................................................................................................... 
8- STUDY DESERTION........................................................................................................ 
9- MODULES AND PROCEDURES FOR DATA COLLECTION AND 
MANAGEMENT………………………………………………………………………… 
10- ETHICAL CONSIDERATIONS ..................................................................................... 

 
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10.1 Patient protection ....................................................................................................... 
10.2 Subjects identification – Personal data protection.................................................. 
11- CONFLICT OF INTEREST ............................................................................................ 
12- DATA OWNERSHIP ........................................................................................................ 
13- PUBLICATION POLICY ................................................................................................ 
14- TIMING OF THE STUDY................................................................................................ 
15- BIBLIOGRAPHY ............................................................................................................. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
1 Synopsis  

 
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Title
Motor performance modulation after total knee replacement 
 
 
Study Coordinator 
Roberto Gatti 
Protocol’s number  
CLF18/06 
Protocol’s date 
07-11-2018 
Background  
 
 
Functional recovery after total knee replacement (TKR) is 
characterized by incomplete recovery of muscular strength due 
to arthrogenic muscle inhibition (AMI) and difficulty in 
functional level self-estimation. Moreover, the widely described 
alteration of sensory feedback can influence the ability to 
modulate motor performance in these patients. 
To date, no studies have investigated the ability to modulate the 
motor performance in patients with TKR with respect to healthy 
subjects.   
Population and selection 
criteria 
 
In this study, 20 patients who undergo TKR and 20 healthy 
subjects will be enrolled. Inclusion criteria are: age between 40 
and 80 years, TKR for primary knee osteoarthritis, knee flexion ≥ 
90° and complete knee extension. Patients must be able to 
perform a sit to stand on a 46 cm chair and to walk for 50m 
without aids. Exclusion criteria are: TKR following traumas, 
previous tibial or femoral osteotomy, partial or complete 
revision, cognitive impairments, other disorders able to influence 
motor or functional recovery.  
 
 
Study design  
This is a prospective observational study. Patients will be 
enrolled from June 2019 to October 2019. After the completion 
of the trials, we will proceed with data analysis. 
 
 

 
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Objectives 
Primary 
endpoint is to investigate motor performance 
modulation during a leg extension, sit-to-stand and walking (10 
Meters Walking Test) tasks. Secondary endpoint is to investigate 
pain, rate of perceived exertion and load symmetry during all 
tasks. TKR group will be evaluated the day before surgery (T0) 
and at 5 days (T1), whereas healthy subjects will perform two 
evaluation sessions at a distance of 5 days.  
Statistical Methods and Data 
analysis.  
Normality and homogeneity of demographic variables will be 
evaluated at the end of data collection.  Differences within-group 
from T0 to T1 and between TKR group and healthy subjects will 
be investigated with t Student test or Wilcoxon-Mann-Whitney 
test.   
Ethical considerations 
 
This is and observational study involving healthy subjects and 
TKR patients. The assessment procedures will be performed 
according to previous studies described in literature and without 
adverse effects. The assessments will be conducted in the Motion 
Analysis Lab of Humanitas Research Hospital. 
 
 
Timeline 
 
 
 
 
 
Patients enrolment: July 2019 - October 2019  
Data analysis: November 2019 - December 2019 
Report Presentation: January 2020 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
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2 Background and introduction 
Knee osteoarthritis is a common disease in patients over 60 years old (Heidari, 2011). Total knee 
replacement (TKR) is a definitive treatment able to relief pain and improve function and quality of 
life. (Callahan, 1994; da Silva et al., 2014). In spite of rapid functional recovery, some deficits, 
such as the incomplete restoration of muscular strength, can persist for several months after this 
type of surgery. The decreased muscular strength seems to depend on the reduced efficiency in  
neuromuscular activity (arthrogenic muscular inhibition - AMI) rather than muscle atrophy 
(Kauppila et al., 2010; Roos et al., 2011; Smith et al., 2014) (Pietrosimone et al., 2011). In fact, 
AMI cam be explained through a spinal and supraspinal excitability modification due to the 
alteration of the sensory feedback from the damaged joint (Rice et al., 2010). It affects not only 
muscles of the operated limb, but also muscles of the non-operated side (Urbach D et al., 2002). 
Moreover, a lack of awareness of functional level represents another feature of patients after TKR. 
To date, only a single study have investigated this aspect in patients with musculoskeletal disorders, 
highlighting the trend to underestimate their functional level (Fisher et al., 2003). However, these 
deficits can also affect the ability to modulate and generate muscle force during the execution of 
motor and functional tasks. 
 
3 Rationale of the study 
The ability to modulate the performance during motor and functional tasks represents a measure of 
neuromuscular control (Dover G et al 2003). To our knowledge, no studies have evaluated this 
ability in patients after TKR with respect to healthy age-matched subjects. Our clinical observations 
and the neurophysiological rationale underlying the deficits of these patients lead us to hypothesize 
the reduction of this ability after TKR.  
 
4 Study objectives  
4.1 General objectives  
The aim of the study is to investigate the ability to modulate the motor performance during motor 
and functional tasks in subjects undergoing TKR. 
 
4.2 End-points  
4.2.1 Primary endpoint 
 
The primary endpoint is to investigate the ability to modulate the motor performance in subjects 
after TKR during a knee extension, sit-to-stand (STS) and walking (10 Meters Walking Test – 
10MWT) tasks. Knee extension will be performed using an isokinetic dynamometer (Ω = 60 °/s) 
and the peak torque (PT) will be measured. The difference between the PT-target and the PT-
observed will be computed in order to quantify the Force Reproduction Error (FRE). The STS will 
be evaluated using two force platforms (BTS P-6000, BTS, Italy) in order to detect the Ground 
Reaction Force (GRF) and to calculate the difference between the GRF-peak and body weight 

 
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(Overshoot-OS). The error between OS-target and OS-observed will be calculated. Finally the 
10MWT will be used to measure the walking speed. The difference between the “target speed” and 
the “observed speed” will be calculated.  
 
4.2.2 Secondary endpoint 
The self-perceived pain (Visual Analogue scale - VAS), the rate of perceived exertion (modified 
Borg scale) and the perceived symmetry of load during these tasks will be assessed. Any correlation 
among these variables and the ability to modulate the motor performance will be investigated.  
 
 
5 Selection criteria 
5.1 Inclusion criteria 
Inclusion criteria: 
• Age between 40 and 80 years old 
• TKR due to primary knee osteoarthritis 
• Flexion ≥ 90° and complete knee extension  
• Ability  to perform STS from a 46 cm chair without the use of the upper limbs 
• Ability to walk for 50 meters without aids 
5.2 Exclusion criteria 
Exclusion criteria: 
• TKR for traumatic events 
• Tibial or femoral osteotomy 
• Partial or total TKR revision 
• Cognitive and psychiatric disorders 
• Neurological or musculoskeletal disorders able to affect functional or motor recovery. 
 
 
 
Healthy subjects will have to match all the eligibility criteria except “intervention of TKR for 
primary knee osteoarthritis”. 
 
 
 
6 Study design  
This is a prospective observational study and it will take place at the Motion Analysis Lab of 
Humanitas Reasearch Hospital.  
 

 
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6.1 General design  
Twenty subjects undergoing TKR and twenty age-matched healthy subjects will be enrolled in the 
study. Patients will be evaluated the day before (T0) and five days after (T1), whereas healthy 
subjects will undergo two evaluation sessions at 5 days distance. The evaluation will start with the 
STS, performed using a 46 cm chair without armrests. The chair will be placed adjacent to the two 
force platforms and a physiotherapist will standardise the subjects’ position. In particular, the trunk 
will be placed in vertical position and the hips and knees will be set at 90° flexion (using a 
goniometer), whereas the feet will be placed equidistant (inter-malleolar distance of 20 cm). 
Twenty-one retro-reflective markers will be placed on lateral malleolus, between the heads of the 
second-third metatarsus, heel, lateral surface of the tibia, lateral condyle and lateral surface of the 
femur, apex of the iliac crest and acromial angle of both sides. Other five markers will be placed on 
sacrum (S2), seventh cervical vertebrae (C7), eighth thoracic vertebrae (T8), incisura jugularis and 
xiphoid process. This marker-set will allows us to monitor the kinematics of the trunk, hip and knee 
during the task, as well as to standardise the starting position of the subjects. All participants will be 
asked to perform three STS with their hands crossed over the chest. In particular, they will be asked 
to perform the first task at maximum speed, the second one at 50% of maximum speed and the third 
one at 25% of maximum speed. All tasks will be repeated twice without giving any feedback on 
participants’ performance. Subsequently, the knee extension task will be performed with both lower 
limbs using an isokinetic dynamometer. The subjects’ position will be standardized (hips and knees 
at 90° flexion) and they will be asked to perform three knee extensions for each limb at   60 °/s 
speed starting from 90° flexion. In particular, they will be asked to perform the first task at 
maximum force, the second one at 50% of maximum force and the third one at 25% of maximum 
force. The same procedure will be repeated with the contralateral lower limb. 
The 10MWT will be performed only three times because in order to reduce any risk of fall. Subjects 
will be asked to walk for 10 meters without aids at maximum speed, at 50% and 25% of maximum 
speed. Each trials will be spaced with 1 minute of rest. 
Standardized instructions will be provided by the same physiotherapist before each test and at the 
end of each task, pain (VAS Scale) and perceived exertion (modified BORG Scale) will be 
evaluated. Finally, only for STS the self-perceived load symmetry will be evaluated using a specific 
scale. It consists of a 20 cm line with two ends respectively defined as "maximum load on the left" 
and "maximum load on the right". Subjects will have to put a tick along the line according to their 
perception of load distribution. A numerical score will be obtained by measuring the distance (in 
centimeters) between the tick and the ends of the line. 
Finally, subjects will fill in KOOS and IPAQ scales in order to monitor the knee function during the 
activities of daily living, its impact on quality of life and their level of physical activity. 
 
 
7 Statistical considerations  

 
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7.1 Sample size  
This is a pilot study and no normative data are available. There are no studies in literature aimed at 
assessing the ability to modulate the motor performance in patients after TKR. However, the few 
studies assessing the ability to reproduce different force levels at the level of the upper limb, have 
enrolled a small sample size (Mugge W et al., 2015). Therefore, a sample of 40 subjects (20 per 
group) will be considered in order to estimate any change in outcome measures. 
 
7.2 Analysis  
Statistical analysis will be performed at the end of data collection using SPSS 20.0 software for 
Windows. Categorical variables will be described in terms of proportion, whereas continuous 
variables in terms of mean and standard or median deviation and interquartile range. The 
assumption of normality will be checked using the Kolmogorov-Smirnov test. Paired t-test for or 
the Wilcoxon test will be used to investigate any within-group difference over time. Student's t-test 
for independent samples or the Mann-Whitney test will be used to assess any difference between 
TKR patients and healthy subjects at T0 and T1. The level of significance will be set at α=0.05. 
 
8  Drop-out 
Individuals who will decide to withdrawn the study will be immediately excluded.  
 
9 Modules and procedures for data collection and management  
Demographic variables and outcome measures will be entered anonymously in an Excel sheet 
(Annex B). Data will be collected by two investigators in order to minimize any errors and will be 
mantained in electronic format, protected by password.  
 
10 Ethical considerations  
10.1 Patient protection 
The study coordinator ensures that this work will be conducted following the principles outlined in 
the Helsinki Declaration (Annex C) and according to the laws of the country in order to guarantee 
the maximum protection of the study participants. The study will be conducted according to the 
Guidelines (ICH) for Good Clinical Practice.  
 
10.2 Subjects identification – Personal data protection  
Participants’ privacy will be protected and no information will be disclosed to the public. Subjects 
will be identified with an ID code and only researcher who are actively involved in the study can 
have access to the database. Each person will be informed through an appropriate form about the 
protection of personal data. Moreover, each participants will be asked to sign in a written informed 
consent. 
 

 
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11  Conflict of interest 
All study members declare to have no conflict of interest. 
 
12 Data ownership  
In accordance with the Guidelines (ICH) for Good Clinical Practice and considering that this is a 
single-center study. Therefore, the data owner is the Istituto Clinico Humanitas. 
 
13 Publication policy  
At the end of the study, the coordinator will prepare a manuscript containing the results of the 
study. This manuscript, after revision, will be sent to an appropriate scientific journal. All 
publications, abstracts, presentations, manuscripts and slides, including the data of this study will be 
submitted and reviewed. 
 
14 Timeline  
1. Subject enrolment: July 2019 - October 2019  
2. Data Analysis: November 2019 - December 2019 
3. Report presentation: January 2020 
 
15 Bibliography  
 
Heidari B. Knee osteoarthritis prevalence, risk factors, pathogenesis and features: Part I. Caspian J 
Intern Med. 2011, 2(2): 205-212. 
 
da Silva RR, Santos AA, de Sampaio Carvalho Júnior J, Matos MA. Quality of life after total knee 
arthroplasty: systematic review. Rev Bras Ortop. 2014, 49(5): 520-7. 
 
Urbach D, Awiszus F. Impaired ability of voluntary quadriceps activation bilaterally interferes with 
function testing after knee injuries. A twitch interpolation study. Int J Sports Med. 2002, 23(4): 231-
6. 
 
Callahan CM, Drake BG, Heck DA, Dittus RS. Patient outcomes follow-ing tricompartimental total 
knee replacement. A meta-analysis. JAMA. 1994, 271: 1349-57. 
 
Dover G, Powers E. Reliability of Joint Position Sense and Force-Reproduction Measures During 
Internal and External Rotation of the Shoulder Journal of Athletic Training. 2003, 38(4): 304–310.  
 
 
Kauppila AM, Kyllönen E, Ohtonen P, Hämäläinen M, Mikkonen P, Laine V, et al. 
Multidisciplinary rehabilitation after primary total knee arthroplasty: a randomized controlled study 
of its effects on functional capacity and quality of life. Clin Rehabil. 2010, 24: 398-411. 
 

 
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Pietrosimone BG, Hertel J, Ingersoll CD, Hart JM, Saliba SA. Voluntary Quadriceps Activation 
Deficits in Patients with Tibiofemoral Osteoarthritis: A Meta-Analysis. Physical medicine and 
rehabilitation. 2011, 3: 153-62. 
 
Smith JW, Christensen JC, Marcus RL, LaStayo PC. Muscle force and movement variability before 
and after total knee arthroplasty: A review. World J Orthop. 2014, 5(2): 69-79.  
 
Roos EM, Herzog W, Block JA, Bennell KL. Muscle weakness, afferent sensory dysfunction and 
exercise in knee osteoarthritis. Nat Rev Rheumatol. 2011, 7(1): 57-63.  
 
Rice DA, McNair PJ. Quadriceps arthrogenic muscle inhibition: neural mechanisms and treatment 
perspectives. Semin Arthritis Rheum. 2010, 40(3): 250-66.  
 
Mugge W, Onneweer B, Schouten A. Force reproduction error depends on force level, whereas the 
position reproduction error does not. IEEE Trans Haptics. 2015.