Kinesthetic Motor Imagery Training During Immobilization to Improve Wrist Functional Outcome After a Distal Radius Fracture in Women of 45-75 Years of Age
Phase: NA
Conditions: Distal Radius Fracture
Sponsor: University Medical Center Groningen

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1 
 
 
 
 
RESEARCH PROTOCOL 
Kinetic motor imagery training during immobilization to improve wrist functional 
outcome after a distal radius fracture in women of 45-75 years of age 
 
 

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PROTOCOL TITLE: Kinetic motor imagery training during immobilization to improve wrist functional 
outcome after a distal radius fracture in women of 45-75 years of age 
 
Protocol ID 
MIDRF.METc.17-08-2015.v4 
Short title 
Motor imagery in rehabilitation after distal radius fracture 
Version 
5 
Date 
1-8-2016 
Coordinating investigator/project 
leader 
 
D.C. Broekstra, MSc, PhD candidate, research employee 
Dept. of Plastic Surgery 
University Medical Center Groningen, P4.260A 
PO Box 30.001 
9700 RB Groningen 
Principal investigator(s) (in Dutch: 
hoofdonderzoeker/uitvoerder) 
Multicenter research: per site 
 
M.W. Stenekes, MD, PhD, Plastic Surgeon 
Dept. of Plastic Surgery 
University Medical Center Groningen, P4.264 
PO Box 30.001 
9700 RB Groningen 
 
 
Sponsor (in Dutch: 
verrichter/opdrachtgever) 
UMCG 
 
 
Independent physician(s) 
P. van der Meer, MD, PhD, Cardiologist 
Dept. of Cardiology 
University Medical Center Groningen, 5.06 (3211) 
PO Box 30.001 
9700 RB Groningen 
Beeper: 77477 
 
 
 
 
Laboratory sites  
Not applicable. 
 
 
Pharmacy  
Not applicable. 
 
 
 

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PROTOCOL SIGNATURE SHEET 
 
Name 
Signature 
Date 
Sponsor or legal representative: 
<please include name and function> 
 
For non-commercial research, 
Head of Department: 
<include name and function> 
 
 
 
 
Prof. dr. P.M.N. Werker, Head of 
Dept. of Plastic Surgery 
 
 
 
 
 
 
 
Coordinating Investigator/Project 
leader/Principal Investigator: 
<please include name and function> 
 
M.W. Stenekes, MD, PhD 
Plastic Surgeon 
 
 
 
 
 
 
 
 
 

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TABLE OF CONTENTS 
1. 
Introduction and rationale ......................................................................................... 9 
1.1 
Relevance .......................................................................................................... 9 
1.2 
Theoretical framework ..................................................................................... 10 
1.3 
Hypothesis ....................................................................................................... 11 
2. 
Objective................................................................................................................. 12 
3. 
Study design ........................................................................................................... 13 
4. 
Study population ..................................................................................................... 14 
4.1 
Population ....................................................................................................... 14 
4.2 
Inclusion criteria .............................................................................................. 14 
4.3 
Exclusion criteria ............................................................................................. 14 
4.4 
Sample size ...................................................................................................... 14 
5. 
TReatment of subjects ............................................................................................. 17 
5.1 
Investigational product/treatment .................................................................... 17 
5.2 
Use of co-intervention ...................................................................................... 18 
6. 
Investigational medicinal product ............................................................................ 19 
6.1 
Name and description of investigational medicinal product(s) ........................... 19 
6.2 
Summary of findings from non-clinical studies .................................................. 19 
6.3 
Summary of findings from clinical studies ......................................................... 19 
6.4 
Summary of known and potential risks and benefits .......................................... 19 
6.5 
Description and justification of route of administration and dosage .................... 19 
6.6 
Dosages, dosage modifications and method of administration ............................ 19 
6.7 
Preparation and labeling of Investigational Medicinal Product ........................... 19 
6.8 
Drug accountability .......................................................................................... 19 
7. 
Methods .................................................................................................................. 20 
7.1 
Study parameters ............................................................................................. 20 
7.1.1 
Main study parameter/endpoint ................................................................ 20 
7.1.2 
Secondary study parameters/endpoints ..................................................... 20 
7.1.3 
Other study parameters ............................................................................. 21 
7.2 
Randomization, blinding and treatment allocation ............................................. 22 
7.3 
Study procedures ............................................................................................. 23 
7.4 
Withdrawal of individual subjects ..................................................................... 24 
7.4.1 
Specific criteria for withdrawal (if applicable) ............................................ 25 
7.5 
Replacement of individual subjects after redrawal ............................................. 25 
7.6 
Follow-up of subjects withdrawn from treatment .............................................. 25 
7.7 
Premature termination of the study .................................................................. 25 
8. 
Safety reporting ...................................................................................................... 26 
8.1 
Section 10 WMO event ..................................................................................... 26 
8.2 
Adverse and serious adverse events .................................................................. 26 
8.2.1 
Suspected unexpected serious adverse reactions (SUSAR) .......................... 27 

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8.2.2 
Annual safety report .................................................................................. 27 
8.3 
Follow-up of adverse events ............................................................................. 27 
9. 
Statistical Analysis .................................................................................................. 28 
9.1 
Descriptive statistics ........................................................................................ 28 
9.2 
Univariate analysis ........................................................................................... 28 
9.3 
Multivariate analysis ........................................................................................ 28 
9.4 
Interim analysis (if applicable) ......................................................................... 28 
10. 
Ethical Considerations ......................................................................................... 29 
10.1 
Regulation statement ....................................................................................... 29 
10.2 
Recruitment and consent .................................................................................. 29 
10.3 
Objection by minors or incapacitated subjects (if applicable) ............................. 29 
10.4 
Benefits and risks assessment, group relatedness .............................................. 30 
10.5 
Compensation for injury ................................................................................... 31 
10.6 
Incentives (if applicable) .................................................................................. 31 
11. 
Administrative Aspects and Publication ................................................................ 32 
11.1 
Handling and storage of data and documents .................................................... 32 
11.2 
Amendements .................................................................................................. 32 
11.3 
Annual progress report .................................................................................... 32 
11.4 
End of study report .......................................................................................... 32 
11.5 
Public disclosure and publication policy ............................................................ 33 
12. 
REFERENCES ....................................................................................................... 34 
 

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LIST OF ABBREVIATIONS AND RELEVANT DEFINITIONS  
 
ABR 
ABR form, General Assessment and Registration form, is the application form that 
is required for submission to the accredited Ethics Committee (In Dutch, ABR = 
Algemene Beoordeling en Registratie) 
AE 
Adverse Event 
AR 
Adverse Reaction 
CA 
Competent Authority 
CCMO 
Central Committee on Research Involving Human Subjects; in Dutch: Centrale 
Commissie Mensgebonden Onderzoek 
CV 
Curriculum Vitae 
DSMB 
Data Safety Monitoring Board 
EU 
European Union 
EudraCT European drug regulatory affairs Clinical Trials  
GCP 
Good Clinical Practice 
IB 
Investigator’s Brochure 
IC 
Informed Consent 
IMP 
Investigational Medicinal Product  
IMPD 
Investigational Medicinal Product Dossier  
METC  
Medical research ethics committee (MREC); in Dutch: medisch ethische toetsing 
commissie (METC) 
(S)AE 
(Serious) Adverse Event  
SPC 
Summary of Product Characteristics (in Dutch: officiële productinfomatie IB1-tekst) 
Sponsor 
The sponsor is the party that commissions the organisation or performance of the 
research, for example a pharmaceutical 
company, academic hospital, scientific organisation or investigator. A party that 
provides funding for a study but does not commission it is not regarded as the 
sponsor, but referred to as a subsidising party. 
SUSAR 
Suspected Unexpected Serious Adverse Reaction 
Wbp 
Personal Data Protection Act (in Dutch: Wet Bescherming Persoonsgevens) 
WMO 
Medical Research Involving Human Subjects Act (in Dutch: Wet Medisch-
wetenschappelijk Onderzoek met Mensen 

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SUMMARY 
 
Rationale: Distal radius fracture (DRF) is a common injury that may lead to prolonged function 
restrictions, decreased range of motion, reduced grip strength and pain. These symptoms may 
be caused by physical changes due to the injury and/or by the 4-6 weeks immobilization that is 
part of the conservative treatment. However, it might also be that neural changes during the 
immobilization play an important role. Such changes might be prevented by motor imagery 
training during the immobilization period. So, when neural changes are prevented, this may lead 
to a better functional outcome.  
Objective: The objective is to improve the functional outcome in distal radius fracture patients, 
specified as an increase in function, dexterity, grip strength, range of motion, and decrease of 
pain. 
Study design: Parallel group randomized controlled trial, with a post-test only control group 
design. Patients in the experimental group perform motor imagery training during the 
immobilization period, in addition to the regular treatment. Patients in the control group receive 
regular treatment.  
Study population: Female DRF-patients who are conservatively treated by a cast, aged 45-75 
years. The fracture must be a low energy trauma caused by a fall. Patients with a score higher 
than 72 on the internal scale of the Vividness of Motor Imagery Questionnaire (VMIQ) are 
excluded, as well as patients with co-morbidities that might influence the wrist function, or 
motor imagery-ability, and patients with no understanding of Dutch language.  
The patients are randomly allocated to the experimental or control group by restricted 
randomization to ensure equal group sizes. The randomization is conducted with use of PASW 
Statistics 18.  
Intervention: Motor imagery training; 4 times a day 7 minutes of motor imagery training for 3 
weeks (depending on duration of immobilization period).  
Main study parameters/endpoints: The main study parameter is function. Secondary study 
parameters are dexterity, range of motion, grip strength, and pain. 
Nature and extent of the burden and risks associated with participation, benefit and group 
relatedness: During the immobilization period, the patients in the experimental group are asked 
to perform motor imagery 4 times a day, whereby each session takes 7 minutes, so the time 
expenditure is 28 minutes a day. The outcome measures are determined twice in each group; 

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directly after cast removal and two weeks after cast removal. The measurements take place at 
the moments that the patients visit the hospital for a protocolized outpatient visit. Thus, the 
measurements do not require extra hospital visits. 
Although there is only one study that examined the effectiveness of motor imagery training in 
peripheral injuries, many studies are conducted that demonstrate the effectiveness of motor 
imagery training in stroke patients, athletes and healthy subjects. Based on these studies, it is 
expected that motor imagery training will benefit recovery after a distal radius fracture. To our 
knowledge, there are no studies that identified the risks of motor imagery training. Since motor 
imagery training does not contain motion, it is highly unlikely that the intervention is harmful to 
the patients.  

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1. INTRODUCTION AND RATIONALE 
1.1 Relevance 
Distal radius fracture (DRF) is a common injury (1-5). In adults, the incidence rates for women 
are 368 per 100.000 persons per year, and for men 90 per 100.000 persons per year. (6). 
Incidence rates are higher with increasing age, due to a higher tendency to falls. They are also 
higher in women compared to men, mainly due to osteoporosis (4).   
A DRF can be treated either conservatively or surgically by different methods, immobilization by 
plaster cast is one of it. Most DRF’s are treated conservatively, especially when the fracture is 
not impacted, is reducible, stable and the joint surface is not involved. Mostly, a plaster cast is 
applied for 4-6 weeks to avoid the loss of fracture reduction (7). This immobilization period 
causes physical changes like muscle atrophy (8-10) and contractures (11,12).  
Usually, DRF-patients are advised to do exercises after the immobilization period to prevent 
further complications associated with the fracture or the treatment, optimize functional 
recovery, and to be able to achieve normal functioning in activities of daily living again (13,14). 
However, research has shown that many DRF-patients suffer from pain, disability, decreased 
range of motion and reduced grip strength, shortly, but also long after the injury (15-18). It is 
reported that even after a few years, ranging from 2 to 26 years after injury, DRF-patients still 
had function restrictions (18). Also when DRF-patients follow a physiotherapy course or a home 
exercise program, 45-95% still have some form of pain and reduced function (15-17), which are 
most profound on work related and recreational activities (15,16). The fact that physiotherapy 
does not seem to improve the functional outcome (19-24), can partly be explained by high 
energy traumas and osteoporotic fractures (25). Such traumas mostly involve anatomical 
deformations which are related to poor functional outcome (26).  However, in other cases with 
low energy trauma, it is likely that other factors relate to the functional outcome too.  
Limb disuse and immobilization can cause neural changes, such as reorganization in the 
sensorimotor cortex and cerebellum, and changes in excitability of the motor cortex (27-29). 
When this happens during immobilization after DRF, it will partly be responsible for complaints 
as clumsiness and functional restrictions that DRF-patients report (30-33). Motor imagery during 
the immobilization period might prevent (part of) these neural changes. Motor imagery is the 
mental process by which a subject performs an action mentally, and it has been found that 
during motor imagery, overlapping cortical areas are activated as during real execution of the 
same movement (34-37).  So, motor imagery training of wrist movements during the 

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immobilization period following a DRF might prevent neural changes caused by limb disuse, 
which might underlie part of the remaining problems of these patients. Therefore, the aim of 
this study is to determine whether motor imagery training during the immobilization period 
following a DRF might prevent functional decay as result of limb disuse on short term. This 
might lead faster to a better functional outcome.  
This study contributes to the existing knowledge of the effectiveness of motor imagery training, 
and it provides new knowledge about the effect of motor imagery during immobilization after 
peripheral injury. Furthermore, when it is found that motor imagery during immobilization 
following a DRF is beneficial, a simple and cheap rehabilitation method is found that can be used 
in addition to existing rehabilitation methods in treating DRF. When DRF-patients recover more 
quickly, health costs will decrease, and patients will be able to return to work and to normal 
daily activities earlier. This is an important aspect, because it is found that work related activities 
and recreational activities are affected most and the most prolonged (15,16).  
 
1.2  Theoretical framework 
They say ‘Use it or lose it’ when it comes to the health of the brain. This is demonstrated by the 
finding that limb disuse and immobilization cause cortical changes (38,39). This might be caused 
by diminished afferent input. Many studies have shown that the absence of afferent input, 
caused by injuries, diseases, or anesthesia, leads to cortical reorganizations (40-44). Areas in the 
sensory and motor cortex that do not receive input, will be taken over by adjacent areas 
(42,44,45). This process reflects the plasticity of the brain, changes in peripheral structures can 
cause large cortical reorganizations (46). It is therefore suggested that absence of efferent 
output causes such cortical reorganizations too.  
The fact that conservative treatment of DRF involves a longer period of immobilization, suggests 
that the immobilization itself is partly responsible for complaints as clumsiness and functional 
restrictions following DRF (30-32), which would mean that immobilization causes undesirable 
effects. The immobilization itself cannot be avoided, but the corresponding neural changes 
might be, by using motor imagery. Motor imagery is the mental state in which an individual 
performs an activity mentally and explicitly feels himself performing it, without actually 
performing the activity physically (47). This mentally rehearsing of activities and movements is 
used as treatment method of many diseases of the central nervous system, like Parkinson’s 
Disease (48) and stroke (49-53). Although motor imagery training is found to be effective in 

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enhancing complex motor skills (54-56), strength (55,57), and reaction time (55) in athletes, 
little research has been published to determine the effect of motor imagery on recovery after 
peripheral injuries, such as a hand injury. One study provides evidence that motor imagery is 
beneficial in rehabilitation following immobilization after hand injury (31).  
1.3 Hypothesis 
We hypothesize that motor imagery training during the immobilization period improves 
functional outcome, specified as an increase in function, dexterity, grip strength and range of 
motion, and a decrease in pain. 

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2. OBJECTIVE 
The objective is to determine whether motor imagery training during the immobilization period 
in DRF patients, leads to an improved functional outcome, specified as increasing function, 
dexterity, grip strength, range of motion, and decreasing pain. 

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3. STUDY DESIGN 
The above hypothesis can be tested by conducting a parallel-group randomized controlled trial.  
The duration of this study is 5 weeks, depending on the length of the immobilization period. The 
patients will be measured during their visits to the hospital. The first measurement is conducted 
directly after removal of the cast. The second measurement is two weeks later, when the 
patients visit the hospital for their check-up appointment. A schematic view of the study is given 
below: 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Distal radius fracture 
- 45-75 years old 
- women 
- conservative treatment 
-  internal VMIQ score ≤ 72  
Motor imagery training 
No intervention 
T1, directly after cast removal 
T1, directly after cast removal 
T2, 2 weeks after cast removal 
T2, 2 weeks after cast removal 
 Experimental group 
Control group 

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4. STUDY POPULATION 
4.1 Population 
Participants are selected among distal radius fracture patients who are conservatively treated by 
plaster cast, or by closed reduction followed by plaster cast, from the University Medical Center 
Groningen. Female patients aged between 45-75 years will be included, because DRF is most 
common in women of 45-75 years of age (58). Patients are excluded when the internal (first 
perspective) VMIQ-score is higher than or equal to 72 points. This indicates that they are unable 
to perform motor imagery adequately. 
 
4.2 Inclusion criteria 
- 
Distal radius fracture patients diagnosed after radiological assessment 
- 
Female patients 
- 
Aged between 45-75 years 
- 
Conservative treatment by plaster cast, or closed reduction followed by plaster cast 
- 
Low energy trauma caused by fall  
 
4.3 Exclusion criteria 
- 
Internal Visual Motor Imagery Questionnaire-score ≥ 72 
- 
Intra-articular, communitive fractures of the distal radius 
- 
Complications likely resulting in worse functional outcome (e.g. dislocation) 
- 
High energy trauma (such as car accidents or by falls from height) 
- 
Pre-existent upper-extremity disorders 
- 
No understanding of Dutch language 
 
4.4 Sample size 
This is the first study that investigates the functional outcome effect of motor imagery training 
during the immobilization period in DRF-patients. Therefore, the sample size calculation cannot 
be based on data of an imagery intervention during immobilization on function after a DRF. In 
this study, function is the primary outcome variable, and it is measured using the Patient Rated 
Wrist/Hand Evaluation (PRWHE). This instrument is derived from the Patient Rated Wrist 
Evaluation (PRWE). The only difference between the PRWE and PRWHE is that the PRWHE 
contains extra questions about aesthetics. It still contains the originally validated questions, 

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format and scoring system. The added questions about aesthetics are not part of the scoring. 
Therefore, it can be treated as the PRWE (59). The PRWE is proven to be the most responsive 
instrument to measure outcome in DRF-patients (60), as it measures disability during usual and 
specific activities and also documents pain. Subjects can score from 0 to 100 on the PRWHE; 0 
indicates no problems at all and 100 indicates large functional difficulties and severe pain. The 
sample size calculation will be based on the expected outcomes of motor imagery training on 
the PRWHE.  
 
Description of calculation process 
A previous study has described  the change of the PRWE-score over time as a result of the 
process of natural recovery after a DRF (61). Based on the results of this study, a mathematical 
model was created using Matlab R2010a that estimates the PRWHE-scores between data 
collection moments. This way, a model was build to estimate the natural recovery process with 
respect to the outcome of the PRWHE. Using this model, it could be determined what the 
decrease of the PRWHE-score is, two weeks after cast removal. The results of this model 
showed that a decrease of 10 points can be expected between the first (T1) and second 
measurements (T2). This decrease is due to natural recovery, and therefore, we expect it to be 
present in both groups. 
Based on expert’s knowledge, we find a 1 week lead in the functional recovery of the motor 
experimental group on the control group a clinically significant difference. With use of the 
mathematical model, the change in the PRWHE-score after 1 week after cast removal could be 
estimated. Next, the mean standard deviation of the PRWHE-scores over time was calculated. 
By dividing the change in the PRWHE-score by the mean standard deviation, the effect size was 
calculated. Now, the sample size could be calculated using the statistical power analysis 
software G*Power 3 (62). 
 
Effect size calculation 
The model describing the change in the PRWHE-score as result of natural recovery following a 
DRF, showed that 1 week after cast removal a decrease of 5.3 points on the PRWHE can be 
expected, which indicates improved function. This would mean that the experimental group 
would show an extra decrease of 5 points on the PRWHE, two weeks after cast removal. 
The mean standard deviation was calculated using the following formula: 

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16
)
)(
1
(
)
(
2
2
2
2
2
2
2
2
2
2
2
y
x
y
x
y
x
y
x
y
x
x
y
y
x
x
x
y
y
x
y
y
y
x
x
n
n
n
n
Y
X
n
n
s
n
n
s
n
n
s
n
s
n
s
n
s
n
s
n
s
n
+
−
+
−
+
+
+
−
−
−
−
+
=

 
 
This provided a mean standard deviation of 26.13… points.  
 
The effect size was calculated using the following formula: 



2
1 −
=
ES
 
This provided an effect size of 0.20…  
 
Settings for sample size calculation 
Test Family: F-tests 
Statistical test: Repeated Measures ANOVA, within-between interaction 
Effect size: 0.20 
Significance level α = 5% 
Preferred power = 80% 
Number of groups: 2 
Number of measurements: 2 
Other settings were kept as the default setting. 
 
Sample size calculation 
The effect size, preferred power, significance level and two-tailed testing were entered in 
G*Power 3. Running the program resulted in a calculated sample size of 52 patients.   

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5. TREATMENT OF SUBJECTS 
5.1 Investigational product/treatment 
The treatment that the experimental group receives is motor imagery training, in addition to the 
regular treatment. The control group receives regular treatment only. Motor imagery is the 
mental state in which an individual performs an activity mentally and explicitly feels himself 
performing it, without actually performing the activity physically (47). This mentally rehearsing 
of a task can be done with two different strategies, by visual or kinetic motor imagery. When a 
person imagines the movement from a third person perspective, it is called visual motor 
imagery. When a person imagines the movement from a first person perspective, as if they are 
performing the movement themselves, it is called kinetic motor imagery (63). Research has 
shown that the neural structures activated during kinetic motor imagery are more similar to the 
neural structures activated during movement execution, than when visual motor imagery is 
performed (64,65). For that reason, the imagery training of DRF-patients in the present study 
will consist of kinetic imagery.  
 
Potential participants are informed about this study by sending them an information letter, 
directly after their initial hospital visit. Patients who want to participate, return an informed 
consent by mail. When the patients who are willing to participate visit the hospital for a medical 
check one week after initial treatment, they are asked to fill in the VMIQ, because the VMIQ-
score is an important inclusion criterion. When the patients reach the inclusion criteria, they are 
included in this study. After that, they receive information about the measurements and 
patients in the experimental group receive also instructions about the motor imagery training.  
The patients in the experimental group do the motor imagery training at home, unsupervised. 
The training starts with 1 minute of relaxation, where the patients are seated comfortably in a 
quiet environment, with their eyes closed. Such relaxation has proven to be promote the 
concentration, and as a consequence, the vividness of motor imagery (66). After that, the motor 
imagery training starts for about 6 minutes. This is well within the recommended maximal 
duration of 20 minutes, and long enough to be effective, as research has shown that the longer 
the imagery training session takes, the smaller the beneficial effect is (67). The patients imagine 
flexion, extension, abduction, adduction, pronation and supination of their injured wrist, 
following the procedure as explained during the instruction. Each set of movements (i.e. flexion-
extension, adduction-abduction, pronation-supination)  is executed in blocks of 10 repetitions. 

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The series of movements (10 times flexion-extension, 10 times adduction-abduction, 10 times 
pronation-supination) is repeated three times. The patients are asked to follow this procedure 4 
times a day, which will take about 28 minutes a day. 
 
5.2 Use of co-intervention 
Patients in the experimental group will do the motor imagery training in addition to the usual 
medical treatment and a usual session of advice by a physiotherapist, which patients receive 
after cast removal. The patients in the control group will receive usual medical treatment and 
session of advice by a physiotherapist, but no motor imagery training. This single session of 
advice by a physiotherapist, is part of the standard treatment protocol for DRF’s. The DRF-
patients receive tips how to handle their casted hand. DRF-patients do not receive 
physiotherapy during the immobilization period. Thereby, only DRF-patients with complications 
or with severe affected hand function long term (> 2 weeks) after the immobilization period, will 
be advised to visit a physiotherapist. So, the patients who will be included in the current study, 
will not receive physiotherapy during the study.  
After the last measurements, all patients will be asked whether they followed other 
interventions or received other treatments during the study period. If this is the case, the results 
of that patient will not be included in the statistical analysis, to control for confounding effects.  
 

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6. INVESTIGATIONAL MEDICINAL PRODUCT 
Not applicable.  
 
6.1 Name and description of investigational medicinal product(s) 
 
6.2 Summary of findings from non-clinical studies 
 
6.3 Summary of findings from clinical studies 
 
6.4 Summary of known and potential risks and benefits 
 
6.5 Description and justification of route of administration and dosage 
 
6.6 Dosages, dosage modifications and method of administration 
 
6.7 Preparation and labeling of Investigational Medicinal Product 
 
6.8 Drug accountability 
 
 

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7. METHODS 
7.1 Study parameters 
Based on literature about the outcome following a DRF (19-24), and experts’ opinions, we 
decided to use 5 outcome measures. The main outcome measure is function. Other outcome 
measures used are the range of motion, grip strength, dexterity, and pain. 
7.1.1 
Main study parameter/endpoint 
Research has shown that DRF-patients suffer more on long term from function restrictions than 
pain (15,16). Therefore, function is the main outcome measure. Function is measured using the 
Patient Rated Wrist/Hand Evaluation (PRWHE). This instrument is developed to measure 
disability during usual and specific activities, and it also documents pain and aesthetics. The 
PRWHE is derived from the PRWE and contains some extra questions about aesthetics. Because 
the PRWHE retains the originally validated questions, format and scoring system of the PRWE, it 
can be treated as the PRWE (59). A study that critically reviewed the available outcome 
assessment tools, showed that the PRWE is the most responsive instrument to measure 
outcome in DRF-patients (60). The PRWE is a self-rated questionnaire, and its mean completion 
time is 4 minutes (61). It consists of 15 questions, divided in 3 domains; pain, functional 
activities, and usual activities. The patients have to rate the severity of their pain or disability in 
different situations. The final score of the PRWE and PRWHE lies between 0-100, where 0 
represents the best and 100 represents the worst outcome. The PRWE is found to be reliable 
and valid, and therefore provides a simple and quick method to measure patient-rated pain and 
disability (61).  
7.1.2 
Secondary study parameters/endpoints 
Secondary outcome measures are dexterity, active range of motion, grip strength, and pain. 
The Sequential Occupational Dexterity Assessment (SODA) is used to determine dexterity. The 
SODA is a valid and reliable instrument that measures bimanual dexterity during activities of 
daily living (68). The SODA consists of 12 tasks, and it takes 20 minutes to complete it. The 
performance on the tasks is scored by the experimenter. The score for each task is build up by 
two different components. One component concerns how the task is performed, and the other 
component concerns the difficulty the patient experiences during the execution of the task. For 
some tasks, only one hand is scored, while for other tasks both hands are scored. The final score 

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ranges from 0-108, where 0 means that the patient is unable to perform any of the tasks, and 
108 means that all tasks were performed as requested without any difficulty (68). 
Range of motion (ROM) is determined using a digital goniometer. Because unrestricted 
movement is essential for normal function, wrist movement in all directions is measured; 
flexion, extension, radial deviation, ulnar deviation, pronation and supination. The literature 
available concerning the amount of measurements needed to provide reliable outcomes, is 
contradicting (69). Some researchers have found that only one measurement is sufficient (70), 
whilst others have found that the average of several measurements is more reliable than one 
measurement (71). It is recommended to use the average of multiple measurements in the ROM 
that shows large variation or a systematic increase (69). We repeatedly measured the different 
ranges of motion, and this provided consistent results. Based on this we decided to use a single 
measurement of each aspect of ROM (i.e. flexion, extension, abduction, adduction, supination, 
and pronation). To control for within-group variability, ROM is measured on both hands. 
Grip strength is important for the execution of many occupational activities (72). It is measured 
using a hydraulic dynamometer, which is found to be reliable and valid (73). Research has shown 
that the position of the wrist can influence the maximal grip strength that can be applied. This is 
especially the case when the wrist is in ulnar or radial deviation, which is one of the deformities 
that is common after a DRF malunion (74). Therefore, it is useful to determine different grip 
strengths; grasp, tip pinch, key pinch, and three-jaw chuck pinch (72,73). The measurements will 
be conducted using a standardized protocol (73), to counter the effects of confounders. The 
mean of three trials has the highest test-retest reliability (73), and therefore, it is decided to 
measure the strength of each grip three times. To control for within-group variability, grip 
strength is measured on both hands. 
Two dimensions of pain are measured using a Visual Analog Scale (VAS) (75); pain intensity and 
pain relief (76). This results in a score between 0 and 100, where 0 represents severe pain and 
low pain relief, and 100 represents no pain and large pain relief.  
7.1.3 
Other study parameters 
Confounding factors that might influence the dependent variables are age, motor imagery 
ability, type of fracture, occupation, sport activities and involvement of their casted hand in 
activities. The patients will be asked for their occupation, sport activities and involvement of the 

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casted hand in activities. The confounding factors will be included in the statistical analysis as 
covariates to control for their influence.  
 
7.2 Randomization, blinding and treatment allocation 
Potential participants are randomly allocated to the experimental or control group before the 
start of the study, i.e. before inclusion. In this way, the potential participants allocated to the 
control group can receive other information about this study than potential participants 
allocated to the experimental group. This is done to prevent occurrence of the bias that might 
be present when the patients in the control group are aware of the working mechanism of 
motor imagery, and its potential benefits. When the patients in the control group know that 
they participate in a study that is conducted to determine whether motor imagery can promote 
the recovery after DRF, it is possible that they perform motor imagery during the 
immobilization, or pay more attention to their injured hand as normal. Such bias cannot be 
detected and may severely confound the results of this study. Therefore, we decided to keep 
the patients in the control group ignorant. 
Because randomization is performed before inclusion, it is likely that some patients will decide 
not to participate, reducing the number of participants in that group. The experience of 2.5 
years inclusion teaches us that the response rate to participate is different for each group 
(experimental group 35%, control group 62%). Therefore, the number of patients who will be 
asked to participate is controlled for this difference. This means that more patients are allocated 
to the experimental group, than to the control group. The random allocation is performed with 
remaining equal group sizes, and equal distribution of the different fracture types (intra-
articular vs. extra-articular distal radius fractures).  
The randomization process is done using PASW Statistics 18. Subject numbers are randomly 
allocated to the experimental or the control group. The order in which the patients receive their 
initial treatment determines their subject number. There is no blinding of the patients, nor the 
researcher is blinded.  
Based on national statistics concerning the diseases and injuries diagnosed on a yearly basis, it is 
expected that 6-7 DRF-patients will be treated in the UMCG every week, and 2-3 of them will be 
women of 45-75 years of age (58).  
 

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7.3 Study procedures 
The study coordinator checks the diagnose lists of the department of Traumatology and 
Orthopedics, and indentifies the female DRF-patients in the age of 45-75 years of age, who are 
conservatively treated. These patients will be randomly allocated to the experimental or control 
group. They receive an information letter and are asked to participate. When they decide to 
participate, they return an informed consent. When the patients visit the hospital for a medical 
check one week after initial treatment, the patients who are willing to participate are asked to 
fill out the Vividness of Motor Imagery Questionnaire. A score of 72 point or less on the internal 
scale (first person perspective) of the VMIQ, is one of the inclusion criteria. Therefore, this 
questionnaire is filled out before inclusion. The score on the VMIQ determines whether the 
patient can participate in the study or not. The patients who are allocated to the experimental 
group will receive information and instructions about the motor imagery training. To promote 
the imagery, the instructions are task-related: 
- 
Flexion and extension: Patients are asked to imagine making a fist and imagine that they 
are slowly knocking on the table with their knuckles, making an exaggerated large 
movement.  
- 
Adduction and abduction: Patients are asked to imagine that there are two dots drawn 
horizontally on the table in front of them. The hand lies between those dots, but there is 
still space between the hand and the dots. They are asked to imagine that they are 
trying to touch the right and the left dot with their little finger and thumb repeatedly, by 
only moving the palm of their hand. 
- 
Pronation and supination:  Patients are asked to imagine that they turn a key back and 
forth, by only using their hand and forearm.  
In addition to these task-related instructions, the movements that have to be imagined are 
demonstrated by the study coordinator. Next, the patients are asked to repeat that movement 
once with their uninjured hand. The patients receive a letter that contains the instructions and 
are asked to repeat this protocol unsupervised at home. To promote their adherence to the 
motor imagery training, the patients in the experimental group will be contacted by phone on a 
weekly basis. To control for bias as a consequence of this extra attention, also the patients in the 
control group will be contacted by phone weekly. 
 

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Three weeks later, which is 4 weeks after injury, the patients return to the hospital to remove 
the cast. At that moment, the first measurements will be performed. All tests will be performed 
by the study coordinator. Directly after cast removal, when they are still at the hospital, 
dexterity, the level of pain and pain relief, grip strength and range of motion will be determined. 
The PRWHE will be performed one day later by phone. Two weeks after cast removal, the 
second measurements will be conducted. Function, dexterity, the level of pain and pain relief, 
grip strength and range of motion will be measured.  
The measurements will take place in the University Medical Center Groningen. The PRWHE and 
the VAS can be scored by the patients themselves, while the measurements with the SODA, 
goniometer and dynamometer will be conducted by the study coordinator. It is expected that 
the first measurements will take 30 minutes to complete, and the second measurements 35 
minutes.  
As explained in chapter 7.1, function is measured using the PRWHE. The PRWHE is a self-
reporting instrument that determines the level of disability during specific and usual activities, 
and also contains some items to determine the level of pain and aesthetics (59). It takes on 
average 4 minutes to complete the questionnaire (61).  
A digital goniometer is used to determine the active ROM. It is expected that the process of 
measuring ROM takes 6 minutes to complete.  
Grip strength is measured using a hydraulic dynamometer (73). The strength of four different 
grips will be determined, according to the protocol as described by Mathiowetz et al. (1984). It is 
expected that the procedure to measure the grip strengths takes 4 minutes to measure both 
sides.  
Dexterity is determined using the SODA. The SODA is a performance-based test, which measures 
the level of disability during activities of daily living (68). We expect that it takes 20 minutes to 
complete it. Instructions of the SODA will be given according to the protocol described by Van 
Lankveld et al. (1996).  
The level of pain and the level of pain relief are determined using a VAS (75), a self-reporting 
scale. It is expected that it only will take a few seconds to complete it.  
 
7.4 Withdrawal of individual subjects 
The patients are free to withdraw from the study at any time, for any reason, and without 
consequences. Patients are withdrawn when the study coordinator thinks that participation by a 

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patient is unsafe, or when the medical condition changes in such way that participation is 
impossible or unadvised.  
7.4.1 
 Specific criteria for withdrawal (if applicable) 
Not applicable. 
 
7.5 Replacement of individual subjects after redrawal 
Individuals will be replaced after redrawal. The first eligible patient that presents at the first aid 
department will be allocated to the group of the redrawn patient, to remain equal group sizes. 
 
7.6 Follow-up of subjects withdrawn from treatment 
Patients who withdraw from the treatment will be followed-up. Because the patients are asked 
to enter the number of motor imagery sessions each day in a diary, it still provides information 
concerning the effectiveness of motor imagery training. 
 
7.7 Premature termination of the study 
When interim-analysis indicates that motor imagery causes deterioration of the hand function, 
causes severe pain, or causes other unwanted effects, this study will be terminated.  
 

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8. SAFETY REPORTING 
8.1 Section 10 WMO event 
In accordance to section 10, subsection 1, of the WMO, the investigator will inform the subjects 
and the reviewing accredited METC if anything occurs, on the basis of which it appears that the 
disadvantages of participation may be significantly greater than was foreseen in the research 
proposal. The study will be suspended pending further review by the accredited METC, except 
insofar as suspension would jeopardise the subjects’ health. The investigator will take care that 
all subjects are kept informed. 
 
8.2 Adverse and serious adverse events 
Adverse events are defined as any undesirable experience occurring to a subject during the 
study, whether or not considered related to [the investigational product / the experimental 
treatment]. All adverse events reported spontaneously by the subject or observed by the 
investigator or his staff will be recorded. 
A serious adverse event is any untoward medical occurrence or effect that at any dose:  
- 
results in death; 
- 
is life threatening (at the time of the event); 
- 
requires hospitalisation or prolongation of existing inpatients’ hospitalisation; 
- 
results in persistent or significant disability or incapacity; 
- 
is a congenital anomaly or birth defect; 
- 
is a new event of the trial likely to affect the safety of the subjects, such as an 
unexpected outcome of an adverse reaction, lack of efficacy of an IMP used for the 
treatment of a life threatening disease, major safety finding from a newly completed 
animal study, etc. 
 
All SAEs will be reported through the web portal ToetsingOnline to the accredited METC that 
approved the protocol, within 15 days after the sponsor has first knowledge of the serious 
adverse reactions.. 
SAEs that result in death or are life threatening should be reported expedited. The expedited 
reporting will occur not later than 7 days after the responsible investigator has first knowledge 
of the adverse reaction. This is for a preliminary report with another 8 days for completion of 
the report. 

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8.2.1 
Suspected unexpected serious adverse reactions (SUSAR) 
Not applicable. 
 
8.2.2 
Annual safety report 
Not applicable. 
 
8.3 Follow-up of adverse events 
All adverse events will be followed until they have abated, or until a stable situation has been 
reached. Depending on the event, follow up may require additional tests or medical procedures 
as indicated, and/or referral to the general physician or a medical specialist. 
 

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9. STATISTICAL ANALYSIS 
9.1 Descriptive statistics 
Patient characteristics are presented using descriptive statistics for the potential confounding 
variables.  
Data of the main outcome measure are of interval level of measurement. The ROM and grip 
strength are of ratio level of measurement. Hence, the descriptive statistics of these outcome 
measures are presented by the mean and standard deviation. Dexterity is measured using the 
SODA, and the data of this instrument are of ordinal level of measurement. Therefore, the 
descriptive statistics are presented by the median and range. Pain is measured using the VAS, 
which provides data of interval level of measurement. So, the descriptive statistics are 
presented by the mean and standard deviation. 
 
9.2 Univariate analysis 
The effectiveness of motor imagery training will be determined with use of a multivariate 
analysis for the parametric data (as described later in chapter 9.3). The non-parametric data are 
analyzed using a Mann-Whitney U test for each variable, to determine whether the groups are 
different. This test is also used when the data is not normally distributed. 
9.3 Multivariate analysis 
With use of a MANOVA, the difference between the experimental and control group will be 
determined for each measurement time and for each variable. There are two factors included in 
the analysis; a between factor ‘group’ and a within factor ‘time’. The hypothesis is tested using 
two-tailed tests, with a significance level of 5%. The data of the patients in both groups will be 
analyzed using an intention to treat analysis.  
 
9.4  Interim analysis (if applicable) 
An interim analysis will be conducted to determine the effect of motor imagery training on hand 
function, dexterity, ROM, grip strength and pain. When the results of this analysis shows serious 
unwanted effects of motor imagery training, this study will be terminated. 

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10. ETHICAL CONSIDERATIONS 
10.1 Regulation statement 
We state that the study will be conducted according to the principles of the Declaration of 
Helsinki and in accordance with the Medical Research Involving Human Subjects Act (WMO) and 
other guidelines, regulations and Acts.  
 
10.2 Recruitment and consent 
The diagnose list of the Emergency department of the University Medical Center Groningen is 
checked daily for DRF. Within 48 hours after initial treatment, an information letter is sent to 
the patients who reach the inclusion criteria to inform them about this study and ask them for 
their participation. As explained in chapter 7.2, potential participants are already allocated to 
the experimental or control group, so the patients in the experimental group receive an 
information letter that is different from the information letter that the patients in the control 
group receive. In this letter, the patients are asked for their participation. When they are willing 
to participate, the patients return a signed informed consent. One week after initial treatment, 
the patients return to the hospital for a check-up appointment. At that moment, they have had 
5-7 days to consider their participation. In the outpatient clinic, the patients who sent back a 
signed informed consent are asked to fill out the Vividness of Motor Imagery Questionnaire 
(VMIQ). The outcome of this test determines the final inclusion or exclusion of the patient. 
Patients who have an internal VMIQ-score > 72 are excluded, because this indicates that their 
ability to perform motor imagery is low. The patients with a VMIQ-score ≤ 72 are included . 
Patients allocated to the control group receive information about the measurements, the 
measurement times and the duration of the study. Patients allocated to the experimental group 
receive the same information about the measurements and duration, but also instructions to do 
motor imagery training. The patients in both groups will receive an information letter, but the 
patients in the experimental group also receive a letter that contains the instructions to do 
motor imagery training.  
 
10.3 Objection by minors or incapacitated subjects (if applicable) 
Not applicable. 
 

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10.4 Benefits and risks assessment, group relatedness 
Benefits 
DRF is a very common injury, especially in elderly women (1-5). In most conservatively treated 
cases, the patients are immobilized by a plaster cast for 4 to 6 weeks (7). Immobilization can 
lead to muscle atrophy (8-10) and contractures (11). Research has shown that immobilization or 
limb disuse can cause cerebral reorganization and decreased excitability of the motor cortex 
(27-29,38), and therefore, can lead to deteriorated motor performance (77). During motor 
imagery, partly the same cortical areas are activated as during execution of movement (34-37). 
So, motor imagery might prevent such neural changes as cerebral reorganization and decreased 
excitability (31). Many studies to determine the effectiveness of motor imagery training are 
conducted in stroke patients, and these studies show that motor imagery is effective in 
regaining arm function (49,50,53,78). By making the patients do motor imagery training during 
the immobilization period, it is expected that these patients have a better outcome when their 
cast is removed. Hereby, these patients might recover more quickly, and possibly reach a better 
final outcome.  
 
Risks 
The risk of participation in this study is negligible. Measuring function and pain with use of 
respectively the PRWHE and VAS which are questionnaires, is not harmful to the patient. The 
measurement of ROM and grip strength is already part of the regular treatment protocol of DRF. 
Therefore, the measurements conducted in this study to determine ROM and grip strength will 
not provide a higher risk than the regular treatment protocol. The SODA is a test concerning the 
performance during activities of daily living. It is performed after cast removal when the medical 
treatment is completed. From that moment, the patients are advised to use their injured hand 
again, so it is improbable that the SODA will lead to a higher risk than the regular procedure.  
There are no studies found that determined the risks of motor imagery training. However, 
because the motor imagery training does not contain motion, it is highly unlikely that the 
intervention will be harmful.  
The patients are measured twice, directly after cast removal and 2 weeks after cast removal. 
The measurements will take place during their regular visits to the hospital for a medical check, 
so this study does not require extra hospital visits.  
 

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Group relatedness 
This study is group-related, as it is evident that this study can be conducted only with 
participation of DRF-patients.  
 
10.5 Compensation for injury 
Insurance 
As the study has no risks, the Medical Ethical Committee of the UMCG decided to authorize 
dispensation from the statutory obligation to provide insurance (art. 4 paragraph 1 of ‘Besluit 
verplichte verzekering bij medisch-wetenschappelijk onderzoek met mensen).  
 
10.6 Incentives (if applicable) 
The patients participating in this study do not receive any special incentives or financial 
compensation.  
 

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11. ADMINISTRATIVE ASPECTS AND PUBLICATION 
11.1 Handling and storage of data and documents 
The research data are handled and stored confidentially and anonymously. The principal 
investigator and study coordinator will have access to the source data. Only anonymous and 
not-personally-identifiable results of interim-analyses will be showed to other physicians and 
researchers who are not involved in this study. For publication purposes, also anonymous and 
not-personally-identifiable data will be used.  
Questionnaires are stored in a cupboard in the office of the principal investigator. The principal 
investigator and study coordinator are the only persons who have access to this cupboard. Data 
files are stored on the personal account of the principal investigator and on the account of the 
study coordinator. These accounts are protected by passwords. The data will be stored for 5 
years. 
 
11.2 Amendements 
Amendments are changes made to the research after a favourable opinion by the accredited 
METC has been given. All amendments will be notified to the METC that gave a favourable 
opinion. 
 
11.3 Annual progress report 
The sponsor/investigator will submit a summary of the progress of the trial to the accredited 
METC once a year. Information will be provided on the date of inclusion of the first subject, 
numbers of subjects included and numbers of subjects that have completed the trial, serious 
adverse events/serious adverse reactions, other problems, and amendments.  
 
11.4 End of study report 
The investigator will notify the accredited METC of the end of the study within a period of 8 
weeks. The end of the study is defined as the last patient’s last visit.  
In case the study is ended prematurely, the investigator will notify the accredited METC, 
including the reasons for the premature termination. 
Within one year after the end of the study, the investigator/sponsor will submit a final study 
report with the results of the study, including any publications/abstracts of the study, to the 

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accredited METC.  
 
11.5 Public disclosure and publication policy 
The investigators have nothing to disclose. The results of this study will be published in a peer 
reviewed scientific magazine. 
 

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