Effects of a Foot Strengthening Program on the Incidence of Injuries, Foot Functionality and Health in Long Distance Runners: a Randomized Controlled Trial.
Phase: NA
Conditions: Leg Injuries
Sponsor: University of Sao Paulo General Hospital

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Effects Of Foot Strengthening on The Incidence Of Injuries In Long Distance Runners  
Clinicaltrials.gov Identifier NCT02306148 
1st May, 2016 (document uploaded in December 12 th 2023, but it was most recently updated and 
approved in May 1st 2016) 
 
 

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STUDY PROTOCOL WITH SAP 
STUDY PROTOCOL FOR A RANDOMIZED CONTROLLED TRIAL AND STATISTICAL ANALYSIS PLAN 
 
Scientific background 
 
Human performance, particularly in one of the most popular sports activities such as running, is 
typically influenced by the state of the musculoskeletal system, either by the level of training and 
conditioning of the biological structures, or by the aging process. Although popular worldwide due to its low 
cost, versatility, convenience [1], and health benefits to people of all ages [2], running is associated with a 
high prevalence of lower extremity injuries (between 19.4% and 79.3%)[3]. The occurrence of injuries limits 
the intended benefits by inducing changes in practice habits [4] or temporary or even permanent cessation 
of running. In addition, injuries lead to increased costs due to medical treatment and/or work absence [5]. 
The understanding of risk factors associated with these injuries, particularly the intrinsic factors, can 
provide important benefits for runners. Among these intrinsic factors, those that are noteworthy include 
biomechanical factors and muscle functionality of the lower extremities, particularly the feet. A systematic 
review by van der Worp et al. [5] included 11 high-quality longitudinal studies and concluded that alterations 
in the biomechanical force distribution patterns, amount of training, history of previous injuries, increased 
index of the navicular drop, and the misalignment of the ankle, knee, and hip are among the main intrinsic 
risk factors for running-related injuries. In addition, extrinsic factors such as the training surface and the type 
of footwear are also relevant risk factors [5]. It is noteworthy that out of these seven diverse risk factors, two 
are related to the foot-ankle complex, demonstrating the importance of maintaining the health and 
functionality of its musculoskeletal structures to prevent injuries. It is also believed that any biomechanical 
alteration in the musculoskeletal system, in particular the foot-ankle complex, broadly influences a runner’s 
functionality, predisposing him/her to a lesser or greater extent to injuries, in addition to the possibility of 
compromising his/her quality of life [2,6]. 
 The foot has a complex structure that can perform a broad variety of functions in different postural 
and dynamic tasks [7,8]. This versatility can only be achieved through its unique arch-shaped architecture 
and its powerful intrinsic and extrinsic muscular activity, which is responsible for the maintenance and 
control of foot arches, postural corrections during disturbances, and torque generation during body 
displacement [9,10]. Even with this unique and specialized structure, a high prevalence of injuries associated 
with running practices occurs in this complex. Among the most common hypotheses used to explain this high 
prevalence are factors such as the excessive ankle/foot pronation in the stance phase of running [11], the 
lowering of the medial longitudinal arch due to navicular drop [12,13], the alteration of rigidity of the plantar 
arches [14], and the increase in impact and acceleration of the tibia during running [15]. 
Evidence suggests the importance of the intrinsic foot musculature, showing that fatigue can cause 
a significant increase in pronation, which is evaluated by the navicular drop [12]. In addition, weakness may 
be a risk factor for falls in the elderly population [16].  Therefore, it is understandable that the specific training 
of foot [13,17] and ankle muscles [18–20] is an important tool that improves functions and functionalities of 
the lower extremities, as has been shown in recent studies [13,19–21].  
The unsupervised practice of a single exercise for the feet (short-foot exercise) four times a week 
promoted a decrease in the navicular drop, an increase in the medial longitudinal arch index, and an increase 
in the functionality quality of the intrinsic foot muscles in asymptomatic individuals [13]. These results were 
maintained one month after the training had been completed. Although the results of Mulligan and Cook 
[13] are promising, the unsupervised practice of an isolated exercise for four weeks may not have been 

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sufficient to cause a transfer of the static gains for a more dynamic task where the foot would be more 
robustly utilized, according to the star excursion balance test. In contrast, one study compared two groups: 
one group performed a four-week period of short-foot exercises, including 100 repetitions for five seconds 
each, and the second group performed a four-week period of towel-curl exercises with the same amount of 
exercise. The controlled study showed that both groups exhibited decreased dislocation of the centre of 
pressure during the modified star excursion test [20]. Therefore, a load increase in the same exercises used 
by Mulligan and Cook [13] resulted in positive effects for postural control.  
The same short-foot exercise was practiced by individuals with flat feet in a randomized controlled 
trial to investigate its effect on the use of foot orthoses [17]. The protocol consisted of three to five sets of 
exercises with five repetitions each, twice a day, for eight weeks. In both study groups, the isometric force 
and the transversal section area of the abductor hallucis muscle were increased after the interventions, with 
a significant increase in the group that used orthoses during exercises. These results demonstrated that even 
in structurally unfavourable conditions, exercise for the foot muscles leads to important strength gains. It is 
noteworthy that even with a well-planned intervention, the lack of a control group and the evaluation of the 
muscle strength alone limit the study conclusions. In addition, the study did not take into account the 
potential clinical and functional changes of the plantar arches, as performed by Goldmann et al. [19]. This 
group of researchers investigated the effects of the hallucis flexors strengthening in the kinetic and kinematic 
of foot and ankle during walking, running, and vertical jumping among university athletes. Training of the 
experimental group consisted of isometric contractions of the hallucis flexors at 90% of the maximum 
voluntary contraction using a dynamometer four times a week for seven weeks. The authors observed a 
significant increase in the performance of vertical jumping and extensor and flexor momentum of the 
metatarsal-phalangeal joint and a gain of 60% to 70% in the strength of the hallucis flexors. This study shows 
that the flexor muscles of the foot respond in a quick and intense manner to training; even for simple training, 
the strengthening of the muscles in question results in global kinematic and kinetic alterations. It would still 
be interesting to determine how long these gains would last after the completion of the intervention and 
whether more elaborate training, involving more muscles and different postures and loads, would alter the 
study outcome, especially with regard to foot biomechanics during locomotor tasks.  
The understanding of the effects of a therapeutic approach focused on the foot biomechanics of 
walking and running, on the strength and functionality of lower extremity muscles will contribute to the 
adoption of more effective therapeutic and preventive strategies for runners. However, no evidence exists 
that supports the efficacy of the therapeutic exercises already used and recommended for the health of the 
feet [7,17,19,20,22] with regard to preventing recurrent injuries in long-distance runners. However, one 
research protocol aims to assess the effects of ankle and hip muscle strengthening and functional balance 
training on running mechanics, postural control, and injury incidence in novice runners with less than one 
year of running experience but without focusing on the intervention of intrinsic and extrinsic muscles of the 
feet [23].  
Therefore, a controlled and randomized clinical trial would determine whether these interventions 
are efficacious by using the incidence of running-related injuries as the primary outcome and following both 
intervention and control subjects during a period of time equal to or greater than one year (the period during 
which the incidence and prevalence of these injuries are reported)[4,24–28].  
It is important to highlight that rehabilitation programs rarely include the intrinsic muscles of the feet 
in their therapeutic protocols. The present proposal uses a new paradigm in which the focus of training and 
preventive interventions in runners is a “ground-up” approach rather than the traditional "top-down" 
approach, which focuses on the hip strengthening. This new approach, advocated by Baltich et al. [23], will 
seek to improve the function of the ankle-foot complex, which is directly associated with the absortion and 
transmission of body forces to the ground and vice-versa during running. 
 

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Objective 
Our aim is therefore to investigate the effects of a "ground-up" therapeutic approach focused on the 
foot-ankle for one year as they relate to 1) the incidence of running-related injuries in the lower limbs of 
long-distance runners, 2) time of occurrence of the first injury, 3) foot health and functionality, 4) strength 
of the intrinsic foot muscles; 5) foot muscle trophism, 6) dynamic foot arch strain and 7) lower-limb 
biomechanics during running.  
 
Methods/Design 
Overview of the Research Design 
A randomized, prospective controlled and parallel trial with blind assessment is designed to study 
the effects of a "ground-up" therapeutic approach focused on the foot-ankle concerning the incidence of 
running-related injuries to the lower limbs of long-distance runners. This trial has an allocation ratio of 1:1. 
Its framework is exploratory to gather preliminary information on the intervention of conducting a full scale 
trial. The trial follows all recommendations established by SPIRIT [29]. 
 Long-distance recreational runners are recruited from the vicinity of the city of São Paulo and 
referred to a physical therapist, who performs the group allocation. The participants are then referred to 
another physical therapist, who performs the initial blind assessment. All runners allocated to the 
intervention group (IG) participate in a protocol of therapeutic exercises for the foot-ankle complex for 8 
weeks, with one session per week supervised by a physical therapist and three sessions per week remotely 
supervised by web-enabled software [30]. They receive access to the web software on the first day and use 
it for 8 weeks. After the 8-week period, the IG runners will continue exercising for 10 more months, 
supervised only by the web software 3 times a week. The runners allocated to the control group (CG) do not 
receive any intervention training, but receive a placebo stretching exercise program.  
All runners will be assessed at baseline and 2 months (end of intervention). They are then assessed 
twice more for follow-up purposes, at 4 and 12 months after the baseline. Assessments will concern the 
incidence of running-related injuries (primary outcome), and all other secondary outcomes.  
The design and flowchart of the protocol are presented in Figure 1. The assessments are performed 
at the Laboratory of Biomechanics of Human Movement and Posture (LaBiMPH) at the Physical Therapy, 
Speech and Occupational Therapy department of the School of Medicine of the University of São Paulo, São 
Paulo, Brazil. 
 

5 
Participants and Recruitment 
This study is currently recruiting patients (study start date: April 2015) 
The eligibility criteria for the volunteer runners are: 
- 
aged between 18 and 55 years old 

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- 
at least one year of running experience  
- 
a weekly training distance greater than 20 km as their main physical activity 
- 
within two months prior to baseline assessment, lack of any lower limb musculoskeletal injury or 
pain that might lead to stopping running practice 
- 
no prior experience within the last year of isolated foot and ankle strength training  
- 
not receiving any physical therapy intervention  
- 
no history of using minimalist shoes for running practice 
- 
no prior experience of barefoot running 
Runners are not selected if they have other neurological or orthopedic impairments (such as 
congenital foot malformations, stroke, cerebral palsy, poliomyelitis, rheumatoid arthritis, prosthesis or 
moderate or severe osteoarthritis), major vascular complications (venous or arterial ulcers), diabetes 
mellitus, sequelae from poorly healed fractures or prior lower-limb surgeries. 
These runners may use the running technique of fore-, mid- or rear-foot ground contact, which will 
be classified by the strike index, according to Cavanagh and Lafortune [31]. 
One hundred and eleven (111) runners will be recruited by radio advertisements, print media and 
running association groups at their site of practice around the city of São Paulo. The potential subjects will 
be interviewed by telephone and, when selected, assessed in the laboratory to confirm all the eligibility 
criteria. This first laboratory assessment represents the baseline condition (blind assessment). 
The runners allocated to the IG will be treated during their locally supervised session at the Physical 
Therapy Department in an ambulatory setting that assists all the physical therapy treatments of the 
Department, providing a reliable therapeutic environment for the intervention. 
 
Randomization, Allocation and Blinding 
The randomization schedule was prepared using Clinstat software [32] by an independent researcher 
(Researcher 1) who was not aware of the numeric code for the CG and IG groups. A numeric block 
randomization sequence will be kept in opaque envelopes.  
After the runners’ agreement to participate and assignment in the research, the allocation into the 
groups will be made by another independent researcher (Researcher 2), who also will be unaware of the 
codes. Only the physiotherapist (Researcher 3) responsible for the locally supervised training knows who is 
receiving the intervention. Researcher 3 will also be responsible for the remote monitoring of the training by 
web software and telephone. One physiotherapist (Researcher 4), who will also be blind to the treatment 
allocation, will be responsible for all clinical, functional and biomechanical assessments. Both 
physiotherapists (researchers 3 and 4) will be blind to the block size used in the randomization procedure.  
To guarantee the blindness of researcher 4, before each evaluation, runners will be instructed not to 
reveal whether they are in the CG or IG; their questions should be asked only to the physiotherapist in charge 
of web software and local training (Researcher 3). 
The trial statistician will also be blind to treatment allocation until the main treatment analysis has 
been completed. 
 
Treatment Arms 
The CG runners will receive a 5-minutes placebo routine of warm-up and muscle-stretching exercises 
to be performed immediately before every running practice during their 8-week study (Additional File 1, table 
3). 
The IG runners will receive a therapeutic foot-ankle exercise protocol for strengthening and 
improving functionality under the supervision of a physiotherapist (Researcher 4) once a week for 8 weeks, 
and a series of foot-ankle exercises to be performed under remote supervision through web software 3 times 

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a week for the full 1-year length of the study (1 year). Both locally (Additional File 1, table 1) and remotely 
supervised therapeutic routines (Additional File 1, table 2) will take from 20 to 30 minutes. In particular, the 
remotely supervised practice will be preferentially performed at home; the web software includes written 
descriptions, photos and videos of each exercise.  
Each week, IG runners will be requested to evaluate the subjective effort of each exercise’s 
performance using a score of 0 to 10 either with the web software or to the physiotherapist during locally 
supervised practice. If the effort score ranges from 0 to 5 and the runner’s performance of each exercise is 
found adequate during the supervised session by the physiotherapist, the exercises will increase in difficulty 
according to the progression chart in tables 1 and 2. If the effort score ranges from 6 to 7, the exercise will 
not increase in difficulty and no progression would be done on that exercise. Thus, the runner remains in the 
same exercise progression until he/she scores 0 to 5 in each particular exercise. Finally, if an IG runner reports 
a score from 8 to 10, the exercise will decrease in difficulty, if possible, until the subject is able to perform it 
without pain or discomfort. 
 
Assessments 
 
A physiotherapist (Researcher 3) who is blind to group allocation will perform all assessments. Each 
assessment will consist of taking a clinical history of personal details, anthropometry, running practice details 
(years of practice, weekly frequency and volume, usual shoe and training surface, number of races and 
whether the runner trains with a running coach), previous orthopedic surgery, other physical activity 
practiced regularly (previous to running practice or simultaneously with running) and an injury history 
concerning the most important risk factors previously published [3,33,34]. 
A foot-health status questionnaire [35] will be used to characterize foot health and functionality. We 
will use a Brazilian-Portuguese version (FHSQ-BR) translated and validated by [36]Ferreira et al.. This 
instrument is divided into three sections. Section I evaluates foot health in four domains: foot pain, foot 
function, footwear and general foot health. Section II evaluates general health in four domains: general 
health, physical activity, social capacity and vigour. Sections I and II are composed of questions with answer 
options presented in affirmative sentences and corresponding numbers. Section III collects general 
demographic data of the individuals [36]. We will not use the scores from Section III. Each domain scores 
from 0 to 100 points, where 100 is the best condition and 0 the worst. 
We will access variations in foot posture of the runners using the Foot Posture Index (FPI) [37]. The 
FPI is a six component measures that allows multiple segment evaluation of foot posture on a static 
measurement and requires that subjects stand in their relaxed stance position looking straight ahead while 
the assessment is in process. The assessment consists on the (1) palpation of the talar head, (2) observation 
of supra and infra malleolar curvature, (3) observation of the calcaneal frontal plane position, (4) observation 
of the bulging in the region of the talo-navicular joint, (5) observation of the height and congruence of the 
medial longitudinal arch and (6) presence of abduction or adduction of the forefoot. Scores reaching from -
12 to +12 and normative values are presented on the literature. 
Subjects will then be assessed for intrinsic foot muscles strength, lower-limb running kinematics and 
kinetics, and dynamic foot-arch strain. The feet of 30% of the participants in each group (41 participants) will 
be imaged by magnetic resonance imaging (MRI) to assess trophism and strength of the foot intrinsic 
muscles; this will be scheduled for the same week of each subject’s baseline measurements. 
After baseline assessment, all subjects will be scheduled for 2 follow-ups assessments, one at 8 weeks 
and the other at 16 weeks. They will maintain contact with the Researcher 3 through the follow-up period by 
the web software, e-mail and telephone.  
 
Running-related Injuries 

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Running-related injuries will be assessed initially at the baseline and will be assessed continually 
throughout the study by the web software. The definition of running-related injury was set according to the 
study of Macera et al. [4]. They stated that any musculoskeletal pain or injury that was caused by running 
practice and that induces changes in the form, duration intensity or frequency of training for at least one 
week will be considered a running-related injury. Only lower-limb injuries will be accounted during the 12-
month period after the baseline assessment; both the incidence and time of occurrence of the first injury will 
be analyzed. 
If any subject presents a new injury during his or her participation in the study, the injury will be 
accounted for and the intervention or placebo intervention will be discontinued, even though all subjects will 
still keep being followed for the completion of the study. 
 
Isometric Intrinsic Foot Muscles Strength 
Strength of the foot’s intrinsic muscles will be assessed in trials using a pressure platform (EMED: 
Novel, Germany) on which the subjects will place their dominant foot while standing with knees extended. 
They will push down as hard as possible using only their hallux and toes, particularly the metatarsophalangeal 
joints and not the hallux interphalangeal joint. A physiotherapist will determine whether the subject lifted 
the heel, and inspect fluctuations in the line of gravity and trunk posture during each trial. If any changes are 
observed in the line of gravity or positioning of the heel or trunk, the trial will be excluded.  Three trials will 
be completed on each foot (left and right) according to Mickle et al. (2006)[38]. Maximum force will be 
normalized by body weight and analyzed for hallux and toes areas separately.  
 
Foot Muscle Trophism and Strength 
One indirect method of measuring foot strength is through MRI, which, combined with other 
techniques, offers good reliability and a way to follow changes in muscular volume [39]. In addition, MRI can 
facilitate understanding the etiology of running-related injuries and rehabilitation of the foot-ankle complex 
[40].  
The MRI of the foot will be performed with a 1.5T system. Foot images will be acquired by the same 
technician using a coil of four channels positioned in the magnetic centre. Participants will be placed in supine 
position with the ankle at 45° of plantar flexion inside the coil. Images will be acquired in the frontal, sagittal 
and transverse planes to confirm the position of the feet, and the subject will be repositioned if necessary. 
T1-weighted images of the entire foot length will be acquired perpendicular to the plantar aspect of the foot 
using a spin-echo sequence (repetition time=500 ms, echo time=16 ms, averages=3, slice thickness= 4 mm, 
gap between slices=0 mm, field of view=120×120 mm, flip angle=90°, matrix=512×512)[41]. The set of images 
will cover the distance between the most proximal and most distal images in which every intrinsic foot muscle 
is visible. 
To assess changes in the cross-sectional area (CSA) and volume of the intrinsic foot muscles, 30% of 
the subjects from each group will have MRI of the foot at three times: baseline, 8 weeks and 16 weeks. 
The CSA will be measured by ImageJ planimeter software [42]. Following, Miller et al. [14] for each 
muscle at each slice and muscle volume will be calculated by multiplying the CSA of all slices for a muscle by 
their linear distance (4mm) and adding these volumes. 
 
Walking and Running Biomechanics 
To ensure maximum reliability, all biomechanical testing sessions will be completed by the same 
researcher. 
Gait and running kinematics will be acquired using three-dimensional displacements of passive 
reflective markers (10 mm in diameter) tracked by nine infrared cameras at 100 Hz (OptiTrack FLEX: V100, 

9 
Natural Point, Corvallis, OR, USA) [43,44]. Some 14 markers will be placed on the right subject’s foot 
according to Leardini’s protocol [45]. Extra markers will be placed at the medial knee joint line, lateral knee 
joint line and bilaterally at the iliac spine antero-superior, superior aspect of the greater trochanter, and 
sacrum. These markers will be used to determine relative joint centres of rotation for the longitudinal axis of 
the foot, ankle and knee. The extra markers from the medial aspect of the knee joint line will be removed 
during the dynamic trial. In addition, three non-collinear reflective markers will be fixed at two technique 
clusters. One of the clusters will be placed in the lateral thigh and the other over the shank.  
The laboratory coordinate system will be established at one corner of the force plate and all initial 
calculations will be based on this coordinate system. Each lower-limb segment (shank and thigh), will be 
modelled based on surface markers as a rigid body with a local coordinate system that coincides with the 
anatomical axes. Translations and rotations of each segment will be reported relative to the neutral positions 
defined during the initial static standing trial. All joints will be considered to be spherical (i.e., with three 
rotational degrees of freedom). The foot will be modeled according to Leardini et al. [45]. That is, the 
calcaneus, mid-foot and metatarsus are considered rigid bodies and the longitudinal axis of the first, second 
and fifth metatarsal bones and proximal phalanx of the hallux will be tracked independently. 
Ground reaction forces will be acquired by a force plate (AMTI OR-6-1000, Watertown, MA, USA) 
with a sampling frequency of 1kHz embedded in the centre of the walkway. Force and kinematic data 
acquisition will be synchronized and sampled by an A/D card (AMTI, DT 3002, 12 bits).  
The subjects will go through a habituation period before the data acquisition to establish confidence 
and comfort in the laboratory environment, and to ensure appropriate movement velocity. To assess lower-
extremity running mechanics, subjects will perform 10 valid over-ground walking trials and 10 valid over-
ground running trials at a constant velocity (9.5 km/h to 10.5 km/s); these will be monitored by two 
photoelectrical sensors (Speed Test Fit Model, Nova Odessa, Brazil).  
The automatic digitizing process, 3D reconstruction of the markers’ positions and filtering of 
kinematic data will be performed using AMASS software (C-motion, Kingston, ON, Canada). Kinematic data 
will be processed using a zero-lag second-order low-pass filter with cutoff frequencies of 6Hz for walking and 
12 Hz for running. Ground reaction force data will be processed using a zero-lag low-pass Butterworth fourth-
order filter with cutoff frequencies of 50Hz for walking and 200 Hz for running.  
A bottom-up inverse dynamics method will be used to calculate the net moments in the sagittal and 
frontal planes of the ankle and knee joints using Visual3D software (C-motion, Kingston, ON, Canada). The 
human body will be modeled by three linked segments (foot, shank and thigh) and the inertial properties will 
be based on Dempster’s standard regression equations. The moment of inertia and location of center of mass 
will be computed assuming the thigh and shank segments as cylinders.  
Calculation of all variables will be performed using a custom-written MATLAB function (MathWorks, 
Natick, MA, USA). Data of only one lower limb (randomly chosen) per subject will be analyzed and compared.  
The following ankle kinematic variables will be analysed: maximum dorsiflexion at foot contact, 
maximum plantarflexion, maximum dorsiflexion at the toe-off and dorsiflexion range of motion (ROM) in the 
sagittal plane during the stance phase. The knee kinematic variables are: maximum flexion at foot contact, 
maximum extension, maximum flexion in the stance phase, ROM on sagittal plane, maximum abduction and 
adduction in the stance phase. The foot kinematic variables are: elevation/drop of the longitudinal arch angle 
and of the first, second and fifth metatarsal bones; rearfoot to forefoot rotation; transverse plane angle 
between first and second metatarsal bones and between second and fifth metatarsal bones; and maximum 
inversion and eversion of the calcaneus (frontal plane). 
The ankle and knee kinetic variables to be analysed are net ankle and knee moments normalized by 
body weight times height and power normalized by body weight in the sagittal plane. The ground reaction 
force variables will be normalized by body weight and are as followings: first peak force (body weight – BW), 
second peak (BW), loading rate 80 [N ms−1], defined as the force rate between 20 and 80% of the contact of 

10 
the foot with the ground during the first peak; loading rate 100 [N ms−1], as determined by the force rate 
between 0 and 100% of the first peak and push-off rate [N ms−1], as defined as the rate of the second peak 
force, between the minimal values until the second peak. 
 
Dynamic longitudinal foot arch strain 
The dynamic longitudinal foot arch strain will be measured according to  Liebermann et al. [46]. The 
measurement involves navicular height (NH), which is the minimum distance from the navicular tuberosity 
relative to the line formed by the first metatarsal head and the medial process of the calcaneus. These three 
landmarks form a plane and NH is independent of rear-foot inversion or eversion. Arch strain can also be 
quantified by fitting a parabola to markers 1–3 (with the navicular head as the vertex) and then measuring 
the average curvature at 100 points evenly spaced along the curve. 
 
Outcome Measurements  
The primary outcome measurement will be the incidence of running-related injuries in the lower 
limbs accounted at the end of 12 months of study.  
The secondary outcomes will be: 1) the time of the occurrence of the first injury along the study 
period (time to event); 2) foot health and functionality (change from baseline); 3) foot, ankle and knee 
kinematics, ankle and knee joint moments, and knee and ankle power during walking and running (change 
from baseline); 4) strength of the intrinsic foot muscles (change from baseline); 5) foot muscle trophism 
(change from baseline); and 6) dynamic foot arch strain (change from baseline). 
 
Interventions 
Runners allocated to the IG will receive a foot-ankle therapeutic exercise protocol for strengthening 
and improving functionality. Part of the exercise protocol (12 exercises) is to be performed once a week 
under the supervision of a physiotherapist for 8 weeks (Additional File 1, Table 1). And a series of eight foot-
ankle exercises is also to be performed 3 times a week remotely supervised by web software (Additional File 
1, Table 2) for the full 1-year completion time of the study. Each session, whether supervised locally or 
remotely, lasts 20 to 30 minutes. The therapeutic exercise protocol is described in details in tables 1 and 2.  
Gradual and progressive difficulty will be offered to the runner, respecting any limitation due to pain, 
fatigue and/or decrease in performance during execution. The runners in the IG will access the web software 
daily, entering their data regarding performance of the foot exercise training and ranking their level of 
difficulty in each exercise from 0 to 10.  
During the locally supervised sessions, the physiotherapist will focus on proper alignment of the foot-
ankle segments, especially if the runner has difficulty in maintaining it, in a way that allows no movement 
compensations. 
Runners allocated to the CG will receive a 5-minute placebo warm-up and muscle stretching exercise 
routine (Additional File 1, Table 3) that they are to perform for 8 weeks immediately before each running 
practice. This placebo training can also be assessed and followed through the web software. The stretching 
exercises are described in detail in Table 3. We hypothesized that a warm-up combined with muscle 
stretching exercises would not have any effect on foot muscular strength and functionality, lower extremity 
biomechanics or injury prevention.  
Both groups will access the web software daily, entering their running practice data (daily training 
duration and volume) and information concerning the occurrence of any injury event. 
The discontinuation criteria for the exercises during any session includes cramps, moderate to 
intense pain, fatigue or any other condition that exposes the runner to any discomfort. 

11 
The discontinuation criteria for the training includes an occurrence of a running-related injury in the 
lower limbs. 
If any subject fails to access the web software for three consecutive weeks without explanation, or 
fails to attend the locally supervised training three consecutive times, that subject will be terminated from 
the study. 
To improve adherence, several actions will be performed by the researchers in the web software. 
Data regarding the subjects running practice, such as training volume, time of practice and occurrence of 
injuries, will be reported to the web software, which will summarize it and make it viewable in the users’ 
area. In addition, for the duration of the study, runners' responses in the web software concerning their foot-
ankle exercise practice and running training will be stored and be accessible to the researchers and subjects 
at any time. If any subject fails to log in to the web software for more than 5 consecutive days, an e-mail will 
be automatically be sent, asking the subject to log in to his or her account and report data on the training (or 
lack of it) for the past week. The physiotherapist responsible for the therapeutic protocol will make phone 
contact with subjects who fail to attend to any of the weekly locally supervised sessions. They will also make 
phone contact with subjects who do not respond to e-mail reminders from the web software. Subjects will 
also be contacted by personal phone calls if data they reported on the web software is found to be 
inconsistent [47]. 
After the period of intervention and after 12 weeks of follow up all runners will be questioned about 
their satisfaction to the training protocol with one question (Did you enjoy doing the exercises?) with three 
answer possibilities (No; A Little; A lot). To avoid evaluation bias, runners will answer this question secretly 
through an online-unidentified form sent to their e-mail. Runners will be informed about the anonymity and 
this form will only be accessed after completion of the study. 
For the duration of the trial, subjects will be advised not to engage in any new physical activity or 
preventive training protocols for the foot and ankle. If any subject cannot avoid such behavior, he or she 
must report this situation during web software access. Concomitant care, such as physical therapy, 
acupuncture or other conventional medical care, will not be permitted except for runners who are injured 
during the study. At the end of 12 months, CG participants that are interested will receive access to the 
software for the foot exercise protocol. 
 
Ethics and Data security 
This trial was approved by the Ethics Committee of the School of Medicine of the University of São 
Paulo (Protocol number nº031/15). Additionally, this trial is registered in ClinicalTrials.gov (a service of U.S. 
National Institutes of Health) Identifier NCT02306148 (November 28, 2014) under the name “Effects of Foot 
Strengthening on the Prevalence of Injuries in Long Distance Runners”. All runners will be asked for written 
informed consent according to the standard forms and the researcher 4 will obtain them. All personal data 
from potential or enrolled runners will be maintained confidential before, during and after the trial by 
encoding participant’s name. All data access and storage are in keeping with National Health and Medical 
Research Council guidelines, as approved. All files will be available from the database published at 
figshare.com. All important protocol amendments will be reported to investigators, review boards and trial 
registration by the Researcher 3. 
 
 
 

12 
Statistical Analysis Plan 
The sample size calculation was made using an effect size of 0.28 (proportion), considering the 
categorical primary outcome variable, which is the incidence of running-related lower-limb injuries [34]. A 
sample size of 101 runners is needed to provide 80% power to detect a moderate effect difference between 
the highest and lowest group injury incidence medians, assuming an alpha of 0.05 and a χ2 statistical design 
– contingency tables (df=1) [48]. Assuming a 10% dropout rate during the study, a sample size of 111 runners 
is needed.  
The statistical analysis will be based on intention-to-treat analysis, and mixed general linear models 
of analysis of variance for repeated measure will be used to detect treatment-time interactions (α = 5%). The 
outcome measures will be compared at baseline, 2 months, 4 months and 12 months. Statistical analyses will 
be performed using the Statistical Package for the Social Sciences (SPSS, IBM; v.26.0). Effect sizes (Cohen´s d 
coefficient) will also be provided between baseline and 2 months and between 2 months and follow-up (4 
and 12 months), if the intervention shows any treatment effect, and effects between 0.2 and 0.5 were 
considered small, between 0.5 and 0.8 were medium, and above 0.8 were large (Cohen, 1988).The missing 
data will be treated by imputation methods depending on the type of the missing data we will face: missing 
completely at random, missing at random, or missing not at random [49] 
 
Analysis for the primary outcome 
To identify any post-allocation between-group differences, descriptive statistics and t-tests will be 
performed (with Pearson's correlation coefficient calculation) for controlling independent variables (age, 
BMI, Arch Index, and FPI), and Chi-square tests will be used to compare dichotomous variables at baseline. 
Any significant correlation larger than 0.30 between a controlling variable and the time-to-injury variable will 
be included in the survival analysis.  
Kaplan-Meier survival analysis will be used to identify differences in RRI risk between allocation 
groups (intervention vs. control) at 12 months. An event is defined as any RRI recorded within the 12-month 
follow up. Data for participants lost to follow up for any reason will be recorded as censored data from that 
time on (e.g., dropouts). Log-rank tests will be performed for comparing RRI risk between groups at 12 
months and every two months. Cox proportional hazards ratio will be calculated to estimate RRI risk at 12 
months. To account for RRI risk factors described in the literature, Cox proportional hazards models will be 
used to impute covariates: (i) previous RRI, (ii) BMI, and (iii) running volume. In order to address the 
proportional hazards assumption for Cox regression, we will use statistical diagnostic tests based on scaled 
Schoenfeld residuals. To address the linearity assumption, we will use Martingale residuals against 
continuous covariates, plotting graphs of the covariates against Martingale residuals of the null cox 
proportional hazards model (BMI, FPI, years of practice, mileage, and pace).  
Mean time-to-injury for the follow up period will be compared between groups using the t-tets. 
Quartile estimation will be used to calculate time-to-injury survival times at which 25%, 50%, and 75% of the 
sample got injured. Then, t-tests will be used for between-group comparisons in each percentile. 
 
Analysis for the secondary outcomes 

13 
The generalized linear mixed model (GLMM) method will be used for univariate analyses, considering 
the following as factors: groups (CG and IG); time of assessment (baseline and after 8 weeks); and the 
interaction effect (time by group). Participants and time will be considered as random effects and groups as 
fixed effects in the GLMM modeling. Univariate comparisons (main and interaction effects) of the estimated 
marginal means will be adjusted with the Bonferroni correction. The comparisons between the pairs of 
estimated marginal means will be made based on the original scale of each of the dependent variables of the 
study.  
Additionally, to capture features of the entire time series of biomehcanical outcomes, a vector field 
analysis of the resultant angles will be conducted using one-dimensional statistical parametric mapping (1D-
SPM), as described elsewhere (Pataky et al., 2013, 2017). 1D-SPM ANOVA followed by post-hoc SPM t-tests 
will be used for 1D variables. Paired (for assessment comparisons) and independent (for group comparisons) 
Hotelling's T2 tests will be used for comparison of 3D variables in a 3D vector field SPM analysis, followed by 
the paired or independent t-test as a post-hoc test with a Sidák correction. 
 
 
 
 
 

14 
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