Oorschot et al.

BMC Neurology (2020) 20:184

https://doi.org/10.1186/s12883-020-01725-0

STUDY PROTOCOL Open Access

Efficacy of a physical activity programme

combining individualized aerobic exercise
and coaching to improve physical fitness in
neuromuscular diseases (I’M FINE): study
protocol of a randomized controlled trial
Sander Oorschot1*, Merel A. Brehm1, Annerieke C. van Groenestijn1, Fieke S. Koopman1, Camiel Verhamme2,
Filip Eftimov2, Judith G. M. Jelsma3, Harald T. Jorstad4, Frans Nollet1 and Eric L. Voorn1

Abstract
Background: In individuals with neuromuscular diseases (NMD), symptoms of muscle weakness, fatigue and pain
may limit physical activity. Inactivity leads to reduced physical fitness, which further complicates daily life functioning.
Due to inconclusive evidence regarding exercise in NMD, the optimal training approach and strategies to preserve an
active lifestyle remain to be determined. The physical activity programme I’M FINE, consisting of individualized aerobic
exercise to improve physical fitness and coaching to preserve an active lifestyle, was therefore developed. The primary
objective of this study will be to evaluate the efficacy of the I’M FINE programme in terms of improved physical fitness
in individuals with slowly progressive NMD, compared to usual care.
Methods: A multicentre, assessor-blinded, two armed, randomized controlled trial will be conducted in a sample of 90
individuals with slowly progressive NMD. Participants motivated to improve their reduced physical fitness will be
randomized (ratio 1:1) to the I’M FINE intervention or usual care. The I’M FINE intervention consists of a six-month physical
activity programme, including individualized home-based aerobic exercise to improve physical fitness (i.e. peak oxygen
uptake), and motivational interviewing coaching (e.g. goal setting, self-management) to adopt and preserve an active
lifestyle. Measurements will be performed at baseline, post-intervention, and at 12- and 18-months follow-up. The primary
outcome is peak oxygen uptake (VO2 peak) directly post intervention. Main secondary outcomes are physical capacity,
muscle strength, self-efficacy, daily activity, quality of life and markers of metabolic syndrome. The primary analysis compares
change in VO2 peak post-intervention between the intervention and usual care group, with analysis of covariance.
Discussion: The I’M FINE study will provide evidence regarding the efficacy of a physical activity intervention on the
physical fitness and active lifestyle over the short- and long-term in individuals with slowly progressive NMD. These
outcomes could potentially improve the (inter)national guidelines for efficacy of aerobic exercise programmes and provide
insight in achieving a more active lifestyle in NMD.
(Continued on next page)

* Correspondence: [email protected]
1
Department of Rehabilitation, Amsterdam Movement Sciences, Amsterdam
UMC, University of Amsterdam, Meibergdreef 9, Amsterdam, The Netherlands
Full list of author information is available at the end of the article

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Oorschot et al. BMC Neurology (2020) 20:184 Page 2 of 10

(Continued from previous page)

Trial registration: (5/11/2018): Netherlands Trial Register NTR7609 (retrospectively registered), https://www.trialregister.nl/
trial/7344. However, the Ethics Review Committee of the Amsterdam Medical Center (AMC) approved the study protocol on
7/11/2017. No adjustments were made to the approved study protocol before the first participant enrolment and
registration. Registration was done after the second participant enrolment and the information in the register corresponds
one on one with the approved study protocol.
Keywords: Neuromuscular diseases, Physical fitness, Active lifestyle, Aerobic exercise, Coaching, Motivational interviewing

Background To sustain the health benefits associated with aerobic

Promotion of physical activity is a central component in exercise, approaches to ensure continuation of exercise
the prevention and treatment of numerous diseases, main- behaviour after completion of the training programme
tenance of functional independence, and improvement of have to be considered, especially in chronic diseases
general well-being and life satisfaction [1–3]. However, in such as NMD [22]. This requires behavioural and/or
slowly progressive neuromuscular diseases (NMD), com- technological solutions including strategies like goal set-
mon symptoms like fatigue [4], poor endurance capacity ting, self-monitoring, and feedback. However, few stud-
[5], and pain [6] lead to increased difficulty when engaging ies on exercise interventions among NMD have focused
in physical activity, leading to reduced physical fitness. on the sustainability of acquired results of exercise pro-
Over 40% of individuals with slowly progressive NMD ex- grammes [23]. Based on other studies of chronic health
perience ‘difficulty exercising’ as main problem impacting conditions such as obesity [24] and heart failure [25],
daily life functioning [7, 8]. In turn, reduced physical fit- motivational interviewing (MI) seems to be a promising
ness and a sedentary lifestyle negatively affect general basis for implementation of a coaching programme in
health and daily life functioning, which is substantiated by interventions to increase physical activity within the
the high prevalence of metabolic syndrome (55%) in this NMD population [26–29].
population [9–11]. Altogether, the vicious cycle of reduced To our knowledge, no previous studies in slowly pro-
physical fitness in slowly progressive NMD may be due to gressive NMD have evaluated the combined effects of
the disease itself (e.g. reduced muscle mass), which is irre- aerobic exercise and coaching to increase and preserve
versible, or to inactivity, which is reversible. In this study, physical fitness. Therefore, our research group developed
we focus on reduced physical fitness due to inactivity. a physical activity programme for individuals with slowly
Breaking the vicious cycle of inactivity and reduced progressive NMD, called IMproving FItness in NEuro-
physical fitness by means of aerobic exercise is a central muscular diseases (I’M FINE). Key components are: 1)
goal of rehabilitation management [12]. Although some comprehensive assessment of the participants’ actual
studies in slowly progressive NMD demonstrated posi- physical fitness and physical activity level, 2) individual-
tive short-term effects of aerobic exercise on physical fit- ized polarized aerobic exercise to improve physical fit-
ness, other studies reported negative results [13–15], ness, and 3) motivational interviewing coaching to attain
thus the overall evidence is inconclusive. Most exercise and preserve an active lifestyle. The primary objective of
studies in NMD used conventional programmes origin- this study is to evaluate the efficacy of the six-month
ally designed for able-bodied individuals. In these pro- I’M FINE intervention on physical fitness in individuals
grammes, intensity prescription was based on estimated with slowly progressive NMD, in comparison with usual
fitness levels, rather than on the individuals’ actual fit- care. Secondary objectives are to evaluate the longer-
ness level. This lack of individualization, which leads to term (6 and 12 months after intervention) effects on
relatively high intensity levels, makes it difficult for indi- physical fitness (sustainability), and to evaluate effects on
viduals with NMD to adhere to their programme and daily activity, quality of life, perceived physical function-
likely contributes to the high dropout rates reported ing, muscle function, markers of metabolic syndrome
[16–18]. Polarized aerobic exercise appears to be a and self-efficacy. Furthermore, the underlying mecha-
promising alternative for conventional training in this nisms of improved physical fitness and daily activity in
population. In this type of training, approximately 75% individuals with slowly progressive NMD will be studied.
of total training volume is performed at low intensities
and approximately 25% performed at high intensities Methods
[19]. This new approach was derived from training Study design
schedules of elite endurance athletes, and has been suc- This is a multicentre, assessor-blinded, two-armed, ran-
cessfully applied in various diseases such as cancer [20] domized controlled trial (RCT), with measurements at
and obesity [21]. baseline (T0), directly after intervention (T1) and at 12
Oorschot et al. BMC Neurology (2020) 20:184 Page 3 of 10

(T2) and 18 months (T3) follow-up (Fig. 1). The I’M  Diagnosed with prior poliomyelitis (confirmed by
FINE study protocol was written in accordance with the signs of residual weakness and atrophy of muscles
Standard Protocol Items: Recommendations for Inter- on neuromuscular examination, and with
ventional Trials (SPIRIT) checklist [30], as included in electromyography); PPS (according to the March of
appendix 1. Dimes criteria [31]); CMT (confirmed by DNA
testing or polyneuropathy compatible with CMT
Study population and positive family history); or other slowly
The study population consists of individuals with slowly progressive NMD (with no effective drug therapy).
progressive NMD, focusing on prior poliomyelitis and  Motivated to improve a reduced physical fitness
Post-Polio Syndrome (PPS), Charcot-Marie-Tooth dis- level.
ease (CMT), and other slowly progressive NMD. Partici-  Aged ≥18 years.
pants will be recruited from six participating hospitals
and rehabilitation centres and through the nationwide And not fulfil any of the following exclusion criteria:
patient organization for NMD ‘Dutch Association for
Neuromuscular Diseases’. The participating centres are  Contraindication for physical activity according to
Amsterdam University Medical Center, location AMC the American College of Sports Medicine (ACSM)
(Amsterdam), University Medical Center Utrecht (Ut- guidelines [32].
recht), Rehabilitation Center Klimmendaal (Arnhem),  Unable to follow verbal or written instructions.
hospital Sint Maartenskliniek (Nijmegen) and Merem  Insufficient competence in the Dutch language.
Medical Rehabilitation (Almere and Hilversum). Poten-  Engaged in an exercise programme (planned,
tially eligible individuals will receive an information let- structured, and repetitive physical activity performed
ter. Subsequently, during a phone call, current attitudes at sufficient intensity to improve or maintain
and beliefs about exercising in NMD, actual physical fit- physical fitness) for a period longer than 4 weeks in
ness and activity levels, and barriers and facilitators to the past 6 months.
physical activity will be discussed. Eligible individuals
willing to participate will be invited for a screening visit. Randomization and blinding
After providing informed consent, individuals will After baseline assessment and study enrolment, partici-
undergo baseline assessment to confirm definitive eligi- pants will be randomized to the intervention or control
bility for inclusion. A participant must meet all the fol- group. Randomization will be stratified for diagnosis and
lowing inclusion criteria: treatment centre. We aim for equal group sizes of the

Fig. 1 Schematic representation of the study design

Oorschot et al. BMC Neurology (2020) 20:184 Page 4 of 10

three different diagnoses. The randomization scheme Supervision consists of six individual face-to-face ses-
will be computer-generated in a Castor EDC database sions and three telephone sessions. The exercise sessions
(Castor EDC, Amsterdam, The Netherlands), which uses consist of multiple exercise bouts per session, which will
random blocks of sequences with variable block sizes of be gradually increased in duration (Fig. 2). Target heart
two and four. The study coordinator, who is not in- rate ranges per exercise bout (i.e. low intensity, high in-
volved in outcome assessments, will perform the tensity and recovery) are based on the AT (Fig. 2c),
randomization. Independent investigators blinded to which will be determined from the maximal exercise test
group allocation will assess outcomes. Participants can- during baseline assessment and evaluated after 8 weeks
not be blinded for group allocation, but will be of training [33]. If the AT cannot be determined from
instructed not to reveal their group allocation to the in- the maximal exercise test or a participant cannot train
vestigators. Analyses will be performed blinded for within the target heart rate ranges (e.g. in case of beta-
group allocation. blocking agents), the training programme will be based
on the Borg scale [34].
Intervention Training sessions will be performed on a stationary erg-
The I’M FINE intervention consists of individualized ometer. Participants will be supplied with the ReVi-app
aerobic exercise and motivational interviewing coaching. (Amsterdam UMC, Amsterdam, the Netherlands) and a
heart rate monitor chest strap (Polar H10, Polar Electro,
Individualized aerobic exercise Kempele, Finland), which connect to each other to con-
Physiotherapists experienced in treating NMD will tinuously monitor heart rate during training. The ReVi-
supervise the individualized aerobic exercise training. app was specifically designed for the I’M FINE aerobic ex-
They will receive a one-day basic training, including gen- ercise programme and will be programmed with the par-
eral information about aerobic exercise in this popula- ticipant’s target heart rate ranges. It provides real-time
tion, training principles, and study-specific information, auditory feedback to support participants in maintaining
such as the session manual and exercise testing. their heart rate within the target range. In addition, partic-
Individualized aerobic exercise consists of a 16-week ipants will register their perceived exertion on the Borg
polarized home-based programme, including two low- Scale (range 6–20) after every exercise bout [35]. All data
intensity sessions below the anaerobic threshold (AT) collected via the ReVi-app are displayed and stored in a
and one high-intensity session above the AT per week. digital dashboard. Physiotherapists will use this dashboard

Fig. 2 Structure and intensity of the training sessions. Figure 2a visualizes the structure of the low intensity training sessions. The blue blocks
represent the low intensity exercise bouts, interspersed by the recovery bouts in red. Figure 2b visualizes the structure of the high intensity
training sessions. The green blocks represent the high intensity exercise bouts, interspersed by the recovery bouts in red. Figure 2c represents the
intensities of the different training sessions and recovery/warming-up
Oorschot et al. BMC Neurology (2020) 20:184 Page 5 of 10

to monitor adherence and possible physical complaints Outcomes

(e.g. muscle soreness, cramps). If necessary, physiothera- Outcome measures for this study are presented in Table
pists will make and register adjustments to training 2. All outcomes will be collected and entered into a
schedules. Castor EDC database by trained investigators. Outcomes
will be assessed at baseline (T0), directly post-
intervention (T1) and 12 months (T2) and 18 months
Motivational interviewing coaching (T3) follow-up.
Parallel to the individualized aerobic exercise, participants
will receive motivational interviewing coaching consisting Primary outcome - physical fitness
of eight individual face-to-face sessions and three tele- The primary outcome is the change in peak oxygen up-
phone sessions, focused on identification of individual be- take (VO2peak). VO2peak is considered the gold standard
liefs and aims, to promote a physically active lifestyle. for physical fitness and recommended as primary out-
Motivational interviewing is a “collaborative, goal-oriented come of exercise studies in NMD [14]. VO2peak is mea-
style of communication with particular attention to lan- sured during a maximal incremental exercise test on a
guage of change. It is designed to strengthen personal mo- bicycle or arm ergometer (Lode Excalibur, Groningen,
tivation for and commitment to specific goals by eliciting The Netherlands) and breath-by-breath respiratory gas
and exploring the person’s own reasons for change within exchange will be measured with MasterScreen CPX
an atmosphere of acceptance and compassion” [36]. (CareFusion, Hoechberg, Germany).
Supervising practitioners will be provided with a manual First, respiratory functions at rest are assessed, including
containing session contents. Core elements are (1): educa- forced vital capacity (FVC), forced expiratory volume in 1
tion on fitness (2), goal setting (3), personal coaching, and s (FEV1), inspiratory capacity (IC) and maximal voluntary
(4) feedback on daily activity (Table 1). ventilation (MVV) [37, 38]. The exercise test will be exe-
Supervising practitioners (occupational therapists or cuted according to international guidelines concerning
movement teachers) have followed a basic course in MI standardization and will be supervised by trained re-
[34, 35], and will participate in a one-day MI refresher searchers. The electrocardiogram and blood pressure are
course. To optimize MI coaching quality, an audio record- monitored during the test [39]. After a three-minute rest
ing of a coaching session will be used to provide feedback period to measure resting metabolism, the test starts with
from an experienced MI-assessor, who will score this ac- 3 minutes of unloaded (arm)cycling, followed by a ramp
cording to the Motivational Interviewing Treatment Integ- protocol with 5–20 W/minute continuous increments in
rity (MITI) scoring list, version 4.2.1 [36]. workload, depending on the participants’ physical fitness
level. Stopping criteria are: VO2 plateau, exhaustion, pedal
frequency dropping below 50 rpm (RPM), and/or partici-
Usual care pant meeting the ACSM stop criteria [32].
Participants are allowed usual care. Usual care may in-
clude use of assistive devices, orthoses, regular physical Secondary outcomes
therapy, and medication. Participants will not be re-
stricted in their activities. Co-interventions will be moni- Daily activity Daily physical activity will be measured
tored throughout the study. using heart rate monitoring (Polar Electro, Kempele,
Finland) during seven consecutive days in daily life to es-
Table 1 Core elements of motivational interviewing coaching tablish total time per day spent in low, moderate and vig-
(1) Education on physical fitness in NMD: Participants receive specific orous intensity activities. An accelerometer (ActiGraph
strategies to promote behavioural change. These strategies include: GT3X+, Health One Technology, Fort Walton Beach, FL)
education about the health benefits of physical activity, advice about
activities that are suitable for individuals with NMD, education about will be used to determine total daily step count.
training principles and polarized training, identifying and overcoming
any perceived barriers to participation in physical activity, and recruiting Health-related quality of life Health-related quality of
social support from spouses, friends or other NMD individuals.
life will be assessed using the Dutch validated version of
(2) Goal setting: Participants set short- and long-term goals regarding the Short Form 36–item Health Survey (SF36). The
activity and participation levels. SMART goals (specific, measurable, ac-
ceptable, realistic, timeline) are formulated in a systematic way. physical health component score (PCS) and mental
(3) Personal coaching: During the coaching sessions, the practitioner
health component score (MCS) will be calculated [40].
guides participants towards a more active lifestyle by integrating
physical activity into daily life. Perceived physical functioning Perceived physical
(4) Feedback on daily activity: Participants will receive a FITBIT Flex functioning will be assessed with the originally developed
(Fitbit Inc., San Francisco, CA), which provides feedback on the level of and validated Dutch ACTIVLIM questionnaire, consisting
physical activity during daily life.
of 22 daily activities for which perceived difficulty in
Oorschot et al. BMC Neurology (2020) 20:184 Page 6 of 10

Table 2 Outcome measures and assessment methods

Visit
T0 T1 T2 T3
Primary outcomes Method
[1] Physical fitness Maximal exercise test on bicycle ergometer or arm X X X X
ergometer
Secondary outcomes
[2] Daily activity Heart rate monitoring and accelerometer X X X X
[3] Health-related quality of life SF-36 questionnaire X X X X
[4] Perceived physical functioning ACTIVLIM questionnaire X X X X
[5] Muscle strength Fixed dynamometry X X X X
[6] Markers of metabolic syndrome and muscle damage Blood analysis, waist circumference, blood pressure X X X X
[7] Self-efficacy Self-efficacy scale X X X X
[8] Physical capacity 6-min walk test or X X X X
6-min push test
Other
Demographic variables (age, gender, education, ethnicity, Questionnaire X
socioeconomic status)
Diagnosis and medical history Questionnaire and medical record X
Abbreviations: T0; baseline assessment, T1; directly post-intervention, T2; 12 months follow-up, T3; 18 months follow-up, SF-36; Short Form 36–item Health Survey

performing the activity is scored on a scale with the op- pressure > 130 mmHg or diastolic blood pressure > 85
tions: impossible, difficult, easy or a ‘?’ [41]. With an on- mmHg; or waist circumference > 102 cm for men or >
line Rasch model, the raw scores will be converted into a 88 cm for women [44]. Furthermore, creatine kinase
linear measure of the participants’ perception of difficulty (CK) will be assessed as an indicator of muscle damage.
in performing activities of daily living [42].
Self-efficacy A Dutch translated version of the Self-
Muscle strength Muscle strength, quantified as maximal Efficacy for Physical Activity (SEPA) scale will be used
voluntary torque (MVT) will be assessed isometrically to determine self-efficacy [45]. This scale assesses partic-
with a fixed dynamometer (Biodex System 4, New York, ipant’s confidence with regard to engaging in exercise in
USA). Depending on the selected training mode, either the presence of the barriers: feeling tired, bad mood, no
the upper (elbow flexors and/or shoulder abductors) or time, on holiday or want to be active outside, but the
lower extremity (knee extensors and/or plantar flexors) weather is bad. Items are rated on a 5-point Likert scale
muscles will be measured. Only muscle groups with scores (1 = absolutely no confidence, 5 = completely confident)
> 3 on the Medical Research Council (MRC) scale [43] will and will translate to a total score for self-efficacy. The
be measured. Three repetitions will be performed and reliability and validity of the SEPA scale has been con-
peak torque in Newton-meters (Nm) used for analyses. firmed in various populations [46–48].

Markers for metabolic syndrome and muscle damage Physical capacity The total distance covered at self-
The blood lipids total cholesterol, high density lipopro- selected comfortable speed and oxygen consumption will
tein (HDL), low density lipoprotein (LDL), very low be determined with the 6-min walk test (6MWT) or 6-
density lipoprotein (VLDL) and triglycerides, together min push test (6MPT) in case participants are wheel-
with glucose, will be assessed from blood samples in a chair bound [49, 50]. During the test, breath-by-breath
fasted state. Waist circumference will be recorded as the VO2 and VCO2 are measured with the K5 portable gas
mean of two measurements with a SECA 201 device analysis system (Cosmed, Rome, Italy). The mean steady
(Seca GmBH & Co Kg, Hamburg, Germany) and resting state VO2 and VCO2 (both in ml/kg/min), and walking
blood pressure as the mean of two measurements with speed (in m/min) will be determined between the fourth
the Datascope DUOtm (Datascope Corp. New Jersey, and sixth minute of the test.
USA). The presence of metabolic syndrome is defined as
meeting three out of five criteria: triglyceride level ≥ 1.7 Attendance rate and adherence
mmol/l; HDL ≤ 1.04 mmol/l for men or ≤ 1.29 mmol/l The attendance rate (number of sessions followed) for
for women; fasting glucose ≥6.1 mmol/l; systolic blood the individualized aerobic exercise and motivational
Oorschot et al. BMC Neurology (2020) 20:184 Page 7 of 10

interviewing coaching will be assessed from the ReVi be used as descriptive statistics. Data will be analysed with
dashboard and logbooks, respectively. Adherence to the SPSS statistical software (IBM Corporation, Armonk, NY,
aerobic exercise programme will be determined based USA), and P ≤ 0.05 used as significance level. We will per-
on time spent in the designated target heart rate zones. form analyses on intention-to-treat basis and include all
Adherence to the coaching sessions will be based on an randomized participants.
overall score for MI quality determined by analysing The primary outcome analysis compares the change
audio recordings of the sessions using the Motivational from baseline to T1 (directly post-intervention) in
Interviewing Treatment Integrity (MITI) scoring system VO2peak between the groups based on ANCOVA, using
[51]. For each practitioner, four audio-recorded sessions the baseline value as covariate. Missing data will be im-
of different participants throughout the study will be puted, first by interpolation if possible, and otherwise by
randomly selected to provide a reliable weighted compe- multiple imputation. The secondary analysis compares
tency score [52]. the change from baseline to T2 (12 months follow-up) in
VO2peak between the groups based on ANCOVA, using
Adverse events the baseline value and stratification factors as covariates.
All adverse events reported by participants or observed Additionally, we will evaluate between-group differ-
by therapists will be recorded and followed until they ences in secondary outcomes at the 6-, 12- and 18-
have abated or a stable situation has been reached. month follow-up assessments (i.e. T1, T2 and T3 re-
spectively), with linear mixed model analysis for re-
Data management peated measurements. Random effects for the intercept
Each participant will be randomly assigned a personal and time will be included in the model. Baseline values,
identification code (ID), which will be used on all data. treatment group, time and a group by time interaction
All data will be registered in a CASTOR EDC database term will be included as covariates. In addition, a ran-
by direct entry. The participant ID list will be stored dom effect for treatment centre will be included to ac-
with password protection and will only be accessible to count for partial clustering within centres. Multivariate
the investigators. All files will be kept for 15 years in se- linear regression analysis for longitudinal data will be
cure conditions. used to investigate associations between participant and
disease characteristics and effect of intervention.
Sample size
We aim to achieve sufficient power to detect differences Withdrawal of participants
in both the short term (T1, primary endpoint) and lon- Participants can leave the study at any time for any rea-
ger term (T2). Because the expected change in VO2peak son if they wish to do so, without any consequences.
is somewhat larger at T1, we used change in VO2peak The investigator can decide to withdraw a participant
from T0 to T2 for the sample size calculation. Based on for urgent medical reasons. Individual participants will
previous studies of exercise programmes in NMD, we not be replaced after withdrawal. Participants who have
expect a difference in change in VO2peak from T0 to T2 withdrawn from the intervention will be asked to partici-
between the intervention and control group of + 2.5 ml/ pate in follow-up measurements.
min/kg (10%) [16, 53, 54].
Based on an effect size of 2.5 ml/min/kg, 1:1 group al-
location, standard deviation of 4.7 ml/min/kg (based on Monitoring
previous studies) and a two sided α of 0.05, a sample size Given the low risk for participants, an independent Data
of n = 76 per group will be needed to obtain 90% power. Safety and Monitoring Board (DMSB) has not been
However, because we will perform an Analysis of Co- established. The investigators are responsible for proce-
variance (ANCOVA), in which the baseline measure- dures of data monitoring. To facilitate compliance with
ment will serve as covariate, a correction for the Good Clinical Practice guidelines, the investigator will
correlation between baseline and follow-up scores permit study-related monitoring, audits, and inspections
should be made [55]. In a previous RCT by our group, by authorized organizations.
the correlation coefficient (r) was 0.71, resulting in n =
38 participants per group (76 x (1-r2)). As we expect a Study status
maximal drop-out rate of 15% based on previous studies From September 2018 to February 2020, 40 partici-
[56, 57], 90 participants will be recruited (45 per group). pants were randomized. In the following year we ex-
pect to recruit the remaining 50 participants, with the
Statistical analyses last participant expected to be randomized in March
Data collected in this study are all quantitative and there- 2021, and finishing the last-follow up measurement in
fore means, medians and percentages (as applicable) will September 2022.
Oorschot et al. BMC Neurology (2020) 20:184 Page 8 of 10

Patient and public involvement knowledge, this is the first RCT in this population that in-
A multidisciplinary working group consisting of rehabili- cludes an exercise behaviour strategy to enhance the sus-
tation physicians, physical therapists, clinical exercise tainability of intervention effects.
physiologists and individuals with different NMD were Once completed as envisaged, this study will be the
invited to participate in several expert meetings to de- largest RCT of the efficacy of a physical activity
velop the physical activity program that forms the basis programme in NMD ever conducted, with outcomes at
for this I’M FINE project. The expert meetings were all levels of the International Level of Classification
used to discuss and adjust the draft versions. Draft ver- (ICF) [58]. This approach will permit detailed evaluation
sions were developed based on findings of two recent of effects at specific ICF levels and possible interactions.
RCTs on aerobic exercise in NMD, experiences of pa- Furthermore, all participants will be followed up for 12
tients and care professionals, and current insights from months after the intervention period. A long follow-up
scientific literature on exercise physiology. A final draft period is clinically relevant, but has not been previously
was sent for feedback to the Dutch association for investigated in this population. Extended follow-up will
neuromuscular diseases and the Dutch professional asso- not only provide information about the maintenance of
ciations for rehabilitation medicine and physical therapy. health effects and long-term results (e.g. the effects on
We also incorporated the suggestions from representa- metabolic syndrome markers), but also about possible
tives of different diagnoses (CMT and PPS) in the I’M long-term adverse events.
FINE project proposal. Due to the strengths of the I’M FINE intervention, we
anticipate lower dropout rates, higher adherence and,
Public disclosure and publication policy consequently, a higher efficacy compared to previously
It is our intention to publish the findings of the study in studied physical activity programmes in NMD. Previous
scientific journals and to present them at scientific meet- studies reported attendance rates, but did generally not
ings. The responsibility for publication and presentation report actual adherence to a programme. In this study
belong to the investigators. Only those investigators the use of the specifically designed ReVi app allows de-
making a significant contribution to the study design tailed monitoring of actual time spent in designated in-
and/or the collection, analysis or interpretation of the tensity zones. All sessions of the coaching programme
I’M FINE trial data will be eligible for authorship. No re- will be audio recorded, enabling an in-depth analysis. A
strictions regarding the public disclosure and publication potential limitation of this study is the lack of available
of the research data have been, or will be made, by the criteria to quantify the extent to which physical fitness
funders. at baseline is reduced due to physical inactivity. Never-
theless, due to study procedures and selection of moti-
Discussion vated participants who are not regularly exercising, we
The I’M FINE study will evaluate the efficacy of a six- expect to recruit a participant group with potential for
month physical activity intervention, combining individ- improvement of physical fitness.
ualized aerobic exercise and motivational interviewing In conclusion, the I’M FINE study will provide evi-
coaching, aimed at improving physical fitness in individ- dence regarding the efficacy of a physical activity inter-
uals with slowly progressive NMD in comparison to vention on the physical fitness and active lifestyle over
usual care. The study has several important strengths, the short- and long-term in individuals with slowly pro-
which are incorporated in the key components of the gressive NMD. These outcomes could potentially im-
I’M FINE intervention and study design. prove the (inter)national guidelines for efficacy of
The individualized aerobic exercise programme was spe- aerobic exercise programmes and provide insight in
cifically designed for individuals with slowly progressive achieving a more active lifestyle in NMD.
NMD and is based on polarized protocols, a relatively new
type of training. This approach would appear to be better Supplementary information
suited to individuals with NMD than conventional train- Supplementary information accompanies this paper at https://doi.org/10.
1186/s12883-020-01725-0.
ing programmes, but has not yet been studied in this
population. Furthermore, the prescription of exercise in-
Additional file 1: Appendix 1 - SPIRIT checklist.
tensity is based on actual fitness levels and therefore better
individualized compared to other studies, which generally
Abbreviations
prescribed intensity based on estimated maximal capacity. 6MPT: 6-min push test; 6MWT: 6-min walk test; ACSM: American College of
Motivational interviewing coaching will be combined with Sports Medicine; ANCOVA: Analysis of Covariance; AT: Anaerobic Threshold;
individualized aerobic exercise to support the transition CMT: Charcot-Marie-Tooth disease; FEV1: Forced Expiratory Volume in 1
Second; FVC: Forced Vital Capacity; HDL: High Density Lipoprotein;
from therapist-supervised exercise to continued physical IC: Inspiratory Capacity; ICF: International Level of Classification;
activity embedded in daily routine. To the best of our ID: Identification Code; I’M FINE: IMproving FItness in NEuromuscular
Oorschot et al. BMC Neurology (2020) 20:184 Page 9 of 10

diseases; LDL: Low Density Lipoprotein; MCS: Mental Health Component 2. Laskowski ER, Lexell J. Exercise and sports for health promotion, disease, and
Score; MI: Motivational Interviewing; MVT: Maximal Voluntary Torque; disability. PM&R. 2012;4(11):795–6. https://doi.org/10.1016/j.pmrj.2012.09.586.
MVV: Maximal Voluntary Ventilation; Nm: Newton-meters; 3. Abresch RT, Carter GT, Han JJ, McDonald CM. Exercise in neuromuscular
NMD: Neuromuscular Diseases; PCS: Physical Health Component Score; diseases. Phys Med Rehabil Clin N Am. 2012;23(3):653–73. https://doi.org/10.
PPS: Post-polio syndrome; RCT: Randomized Controlled Trial; 1016/j.pmr.2012.06.001.
ReVi: Rehabilitation and Vitality (Revalidatie en Vitaal); RPM: Revolutions Per 4. Feasson L, Camdessanche JP, El Mandhi L, Calmels P, Millet GY. Fatigue and
Minute; SEPA: Self-Efficacy for Physical Activity scale; SF36: Short Form 36– neuromuscular diseases. Annales de readaptation et de medecine physique.
item Health Survey; T0: baseline assessment; T1: directly post-intervention; 2006;49(6):289–300, 75-84. https://doi.org/10.1016/j.annrmp.2006.04.015.
T2: 12 months follow-up; T3: 18 months follow-up; VLDL: Very Low Density 5. Nollet F, Beelen A, Sargeant AJ, de Visser M, Lankhorst GJ, de Jong BA.
Lipoprotein Submaximal exercise capacity and maximal power output in polio subjects.
Arch Phys Med Rehabil. 2001;82(12):1678–85. https://doi.org/10.1053/apmr.
Acknowledgements 2001.27390.
Not applicable. 6. Jensen MP, Abresch RT, Carter GT, McDonald CM. Chronic pain in persons
with neuromuscular disease. Arch Phys Med Rehabil. 2005;86(6):1155–63.
Authors’ contributions https://doi.org/10.1016/j.apmr.2004.11.028.
FN, EV, and MB originated the idea for the study, developed the overall 7. Abresch RT, Carter GT, Jensen MP, Kilmer DD. Assessment of pain and
study design and obtained funding for the study. SO, MB, AvG, FK, CV, FE, JJ, health-related quality of life in slowly progressive neuromuscular disease.
HJ, FN and EV contributed to the specific study design. AvG and FK The American journal of hospice & palliative care. 2002;19(1):39–48. https://
contributed to the design of the trial from a rehabilitation medicine doi.org/10.1177/104990910201900109.
perspective, CV and FE from a neurology perspective, HJ from a cardiology 8. McDonald CM. Physical activity, health impairments, and disability in
perspective and JJ regarding the coaching programme. SO is responsible for neuromuscular disease. American journal of physical medicine &
data collection, analysis and interpretation and wrote the manuscript. All rehabilitation. 2002;81(11 Suppl):S108–20. https://doi.org/10.1097/01.Phm.
authors critically revised the manuscript for important intellectual content. All 0000029767.43578.3c.
authors read and approved the manuscript. 9. Menotti F, Laudani L, Damiani A, Macaluso A. Amount and intensity of daily
living activities in Charcot-Marie-tooth 1A patients. Brain and behavior. 2014;
Funding 4(1):14–20. https://doi.org/10.1002/brb3.187.
This study is funded by the Prinses Beatrix Spierfonds (PBS, W.OK17–3) and 10. Rapin A, Etosse A, Tambosco L, Nicomette J, Percebois-Macadre L, Mouret P,
the funding body has peer-reviewed the protocol as part of the grant award et al. Aerobic capacities and exercise tolerance in neuromuscular diseases: a
process. The funders had no influence on the study design; the collection, descriptive study. Annals of physical and rehabilitation medicine. 2013;56(6):
management, analysis, and interpretation of data; writing of the report; or 420–33. https://doi.org/10.1016/j.rehab.2013.04.004.
the decision to submit the report for publication, and had no ultimate au- 11. Aitkens S, Kilmer DD, Wright NC, McCrory MA. Metabolic syndrome in
thority over any of these activities. neuromuscular disease. Arch Phys Med Rehabil. 2005;86(5):1030–6. https://
doi.org/10.1016/j.apmr.2004.09.012.
12. Voorn EL, Koopman F, Nollet F, Brehm MA. Aerobic exercise in adult
Availability of data and materials
neuromuscular rehabilitation: a survey of healthcare professionals. J Rehabil
Not applicable.
Med. 2019;51(7):518–24. https://doi.org/10.2340/16501977-2567.
13. Abresch RT, Han JJ, Carter GT. Rehabilitation management of neuromuscular
Ethics approval and consent to participate disease: the role of exercise training. J Clin Neuromuscul Dis. 2009;11(1):7–
The Medical Ethics Committee of Amsterdam UMC, location Academic 21. https://doi.org/10.1097/CND.0b013e3181a8d36b.
Medical Center (AMC), approved the study protocol (NL62104.018.17), and all 14. Anziska Y, Sternberg A. Exercise in neuromuscular disease. Muscle Nerve.
participating centres granted approval to participate. Important protocol 2013;48(1):3–20. https://doi.org/10.1002/mus.23771.
modifications will be communicated to the accredited METC and only made 15. Voet NB, van der Kooi EL, van Engelen BG, Geurts AC. Strength training and
effective after a favourable opinion from the METC. The researcher who is aerobic exercise training for muscle disease. The Cochrane database of
responsible for data collection (SO) obtains informed consent from each systematic reviews. 2019;12:Cd003907. doi: https://doi.org/10.1002/
participant that is signed and dated prior to any study-related procedures. 14651858.CD003907.pub5.
Participants are able to withdraw from the trial at any time. 16. Hedermann G, Vissing CR, Heje K, Preisler N, Witting N, Vissing J. Aerobic
Training in Patients with Congenital Myopathy. PloS one. 2016;11(1):
Consent for publication e0146036-e. doi: https://doi.org/10.1371/journal.pone.0146036.
Not applicable. 17. Andersen G, Prahm KP, Dahlqvist JR, Citirak G, Vissing J. Aerobic training
and postexercise protein in facioscapulohumeral muscular dystrophy: RCT
Competing interests study. Neurology. 2015;85(5):396–403. https://doi.org/10.1212/wnl.
The authors declare that they have no competing interests. 0000000000001808.
18. Vissing CR, Preisler N, Husu E, Prahm KP, Vissing J. Aerobic training in
Author details patients with anoctamin 5 myopathy and hyperckemia. Muscle Nerve. 2014;
1
Department of Rehabilitation, Amsterdam Movement Sciences, Amsterdam 50(1):119–23. https://doi.org/10.1002/mus.24112.
UMC, University of Amsterdam, Meibergdreef 9, Amsterdam, The 19. Laursen PB. Training for intense exercise performance: high-intensity or
Netherlands. 2Department of Neurology, Amsterdam Neuroscience, high-volume training? Scand J Med Sci Sports. 2010;20(Suppl 2):1–10.
Amsterdam UMC, University of Amsterdam, Meibergdreef 9, Amsterdam, The https://doi.org/10.1111/j.1600-0838.2010.01184.x.
Netherlands. 3Department of Public and Occupational Health, Amsterdam 20. Klika RJ, Callahan KE, Drum SN. Individualized 12-week exercise training
UMC, VU University Medical Center, de Boelelaan 1118, Amsterdam, The programs enhance aerobic capacity of cancer survivors. Phys Sportsmed.
Netherlands. 4Department of Cardiology, Amsterdam Movement Sciences, 2009;37(3):68–77. https://doi.org/10.3810/psm.2009.10.1731.
Amsterdam UMC, University of Amsterdam, Meibergdreef 9, Amsterdam, The 21. Zapata-Lamana R, Henriquez-Olguin C, Burgos C, Meneses-Valdes R,
Netherlands. Cigarroa I, Soto C, et al. Effects of polarized training on Cardiometabolic risk
factors in young overweight and obese women: a randomized-controlled
Received: 4 March 2020 Accepted: 12 April 2020 trial. Front Physiol. 2018;9:1287. https://doi.org/10.3389/fphys.2018.01287.
22. Lai B, Kim Y, Wilroy J, Bickel CS, Rimmer JH, Motl RW. Sustainability of
exercise intervention outcomes among people with disabilities: a secondary
References review. Disabil Rehabil. 2019;41(13):1584–95. https://doi.org/10.1080/
1. Powell KE, Paluch AE, Blair SN. Physical Activity for Health: What Kind? How 09638288.2018.1432704.
Much? How Intense? On Top of What? 2011;32(1):349–65. doi: https://doi. 23. Veenhuizen Y, Cup EHC, Jonker MA, Voet NBM, van Keulen BJ, Maas DM,
org/10.1146/annurev-publhealth-031210-101151. et al. Self-management program improves participation in patients with
Oorschot et al. BMC Neurology (2020) 20:184 Page 10 of 10

neuromuscular disease: a randomized controlled trial. Neurology. 2019; examination of the peripheral nervous system. By Michael O'Brien for the
93(18):e1720–e31. https://doi.org/10.1212/wnl.0000000000008393. Guarantors of Brain. Saunders Elsevier: 2010; pp. [8] 64 and 94 figures. Brain.
24. Gourlan M, Sarrazin P, Trouilloud D. Motivational interviewing as a way to 2010;133(10):2838–44. https://doi.org/10.1093/brain/awq270.
promote physical activity in obese adolescents: a randomised-controlled 44. Grundy SM, Brewer HB, Cleeman JI, Smith SC, Lenfant C. Definition of
trial using self-determination theory as an explanatory framework. Psychol metabolic syndrome. Circulation. 2004;109(3):433–8. https://doi.org/10.1161/
Health. 2013;28(11):1265–86. https://doi.org/10.1080/08870446.2013.800518. 01.CIR.0000111245.75752.C6.
25. Schertz A, Herbeck Belnap B, Chavanon M-L, Edelmann F, Wachter R, 45. Marcus BH, Selby VC, Niaura RS, Rossi JS. Self-efficacy and the stages of
Herrmann-Lingen C. Motivational interviewing can support physical activity exercise behavior change. Res Q Exerc Sport. 1992;63(1):60–6. https://doi.
in elderly patients with diastolic heart failure: results from a pilot study. ESC org/10.1080/02701367.1992.10607557.
Heart Failure. 2019;6(4):658–66. https://doi.org/10.1002/ehf2.12436. 46. Marcus BH, Eaton CA, Rossi JS, Harlow LL. Self-efficacy, decision-making, and
26. Rimmer JH, Rowland JL. Health promotion for people with disabilities: stages of change: an integrative model of physical Exercise1. J Appl Soc
implications for empowering the person and promoting disability-friendly Psychol. 1994;24(6):489–508. https://doi.org/10.1111/j.1559-1816.1994.
environments. Am J Lifestyle Med. 2008;2(5):409–20. https://doi.org/10.1177/ tb00595.x.
1559827608317397. 47. Cardinal BJ, Tuominen KJ, Rintala P. Psychometric assessment of Finnish
27. van der Ploeg HP, Streppel KR, van der Beek AJ, van der Woude LH, versions of exercise-related measures of Transtheoretical model constructs.
Vollenbroek-Hutten MM, van Harten WH, et al. Counselling increases International journal of behavioral medicine. 2003;10(1):31–43. https://doi.
physical activity behaviour nine weeks after rehabilitation. Br J Sports Med. org/10.1207/s15327558ijbm1001_03.
2006;40(3):223–9. https://doi.org/10.1136/bjsm.2005.021139. 48. Mendoza-Vasconez AS, Marquez B, Benitez TJ, Marcus BH. Psychometrics of
28. O'Halloran PD, Blackstock F, Shields N, Holland A, Iles R, Kingsley M, et al. the self-efficacy for physical activity scale among a Latina women sample.
Motivational interviewing to increase physical activity in people with BMC Public Health. 2018;18(1):1097. https://doi.org/10.1186/s12889-018-
chronic health conditions: a systematic review and meta-analysis. Clin 5998-0.
Rehabil. 2014;28(12):1159–71. https://doi.org/10.1177/0269215514536210. 49. Enright PL. The six-minute walk test. Respir Care. 2003;48(8):783–5.
29. Barrett S, Begg S, O'Halloran P, Kingsley M. Integrated motivational 50. Cowan RE, Callahan MK, Nash MS. The 6-min push test is reliable and
interviewing and cognitive behaviour therapy for lifestyle mediators of predicts low fitness in spinal cord injury. Med Sci Sports Exerc. 2012;44(10):
overweight and obesity in community-dwelling adults: a systematic review 1993–2000. https://doi.org/10.1249/MSS.0b013e31825cb3b6.
and meta-analyses. BMC Public Health. 2018;18(1):1160. https://doi.org/10. 51. Moyers TB, Rowell LN, Manuel JK, Ernst D, Houck JM. The motivational
1186/s12889-018-6062-9. interviewing treatment integrity code (MITI 4): rationale, preliminary
30. Chan A-W, Tetzlaff JM, Altman DG, Laupacis A, Gøtzsche PC, Krleža-Jerić K, reliability and validity. J Subst Abus Treat. 2016;65:36–42. https://doi.org/10.
et al. SPIRIT 2013 statement: defining standard protocol items for clinical 1016/j.jsat.2016.01.001.
trials. Ann Intern Med. 2013;158(3):200–7. https://doi.org/10.7326/0003-4819- 52. Jelsma JG, Mertens VC, Forsberg L, Forsberg L. How to measure
158-3-201302050-00583. motivational interviewing Fidelity in randomized controlled trials: practical
31. Foundation MoDBD. Proceedings of the international conference on Post- recommendations. Contemporary clinical trials. 2015;43:93–9. https://doi.
Polio Syndrome. In: Dimes Mo, editor.; May 19, 2000; New York2001. org/10.1016/j.cct.2015.05.001.
32. Ferguson B. ACSM’s guidelines for exercise testing and prescription 9th Ed. 53. Bankole LC, Millet GY, Temesi J, Bachasson D, Ravelojaona M, Wuyam B,
2014. The Journal of the Canadian Chiropractic Association. 2014;58(3):328. et al. Safety and efficacy of a 6-month home-based exercise program in
33. Voorn EL, Gerrits KH, Koopman FS, Nollet F, Beelen A. Determining the patients with facioscapulohumeral muscular dystrophy: a randomized
anaerobic threshold in postpolio syndrome: comparison with current controlled trial. Medicine. 2016;95(31):e4497. https://doi.org/10.1097/md.
guidelines for training intensity prescription. Arch Phys Med Rehabil. 2014; 0000000000004497.
95(5):935–40. https://doi.org/10.1016/j.apmr.2014.01.015. 54. Wiesinger GF, Quittan M, Aringer M, Seeber A, Volc-Platzer B, Smolen J, et al.
34. Borg G. Perceived exertion as an indicator of somatic stress. Scand J Rehabil Improvement of physical fitness and muscle strength in polymyositis/
Med. 1970;2(2):92–8. dermatomyositis patients by a training programme. Br J Rheumatol. 1998;
35. Borg GA. Psychophysical bases of perceived exertion. Med Sci Sports Exerc. 37(2):196–200. https://doi.org/10.1093/rheumatology/37.2.196.
1982;14(5):377–81. 55. Borm GF, Fransen J, Lemmens WA. A simple sample size formula for
analysis of covariance in randomized clinical trials. J Clin Epidemiol. 2007;
36. Miller WR, Rollnick S. Motivational interviewing, third edition: helping
60(12):1234–8. https://doi.org/10.1016/j.jclinepi.2007.02.006.
people change: Guilford publications; 2012.
56. Koopman FS, Voorn EL, Beelen A, Bleijenberg G, de Visser M, Brehm MA,
37. Wasserman K, Hansen JE, Sue DY, Stringer WW, Whipp BJ. Principles of
et al. No reduction of severe fatigue in patients with Postpolio syndrome by
exercise testing and interpretation: including pathophysiology and clinical
exercise therapy or cognitive behavioral therapy: results of an RCT.
applications: Lippincott Williams & Wilkins Philadelphia; 1999.
Neurorehabil Neural Repair. 2016;30(5):402–10. https://doi.org/10.1177/
38. Miller MR, Hankinson J, Brusasco V, Burgos F, Casaburi R, Coates A, et al.
1545968315600271.
Standardisation of spirometry. Eur Respir J. 2005;26(2):319–38. https://doi.
57. Voet N, Bleijenberg G, Hendriks J, de Groot I, Padberg G, van Engelen B,
org/10.1183/09031936.05.00034805.
et al. Both aerobic exercise and cognitive-behavioral therapy reduce chronic
39. Clinical exercise testing with reference to lung diseases: indications,
fatigue in FSHD: an RCT. Neurology. 2014;83(21):1914–22. https://doi.org/10.
standardization and interpretation strategies. ERS Task Force on
1212/wnl.0000000000001008.
Standardization of Clinical Exercise Testing. European Respiratory Society.
58. World Health O. International classification of functioning, disability and
The European respiratory journal. 1997;10(11):2662–89.
health : ICF. Geneva: World Health Organization; 2001.
40. Aaronson NK, Muller M, Cohen PD, Essink-Bot M-L, Fekkes M, Sanderman R,
et al. Translation, validation, and norming of the Dutch language version of
the SF-36 health survey in community and chronic disease populations. J Publisher’s Note
Clin Epidemiol. 1998;51(11):1055–68. https://doi.org/10.1016/S0895- Springer Nature remains neutral with regard to jurisdictional claims in
4356(98)00097-3. published maps and institutional affiliations.
41. Vandervelde L, Van den Bergh PY, Goemans N, Thonnard J-L. Activity
limitations in patients with neuromuscular disorders: a responsiveness study
of the ACTIVLIM questionnaire. Neuromuscul Disord. 2009;19(2):99–103.
https://doi.org/10.1016/j.nmd.2008.11.004.
42. Vandervelde L, Van den Bergh PY, Goemans N, Thonnard JL. ACTIVLIM: a
Rasch-built measure of activity limitations in children and adults with
neuromuscular disorders. Neuromuscular disorders. 2007;17(6):459–69.
https://doi.org/10.1016/j.nmd.2007.02.013.
43. Compston A. Aids to the investigation of peripheral nerve injuries. Medical
Research Council: nerve injuries research committee. His Majesty's stationery
office: 1942; pp. 48 (iii) and 74 figures and 7 diagrams; with aids to the