MS: Multiple Sclerosis; PT: Physiotherapist; ADL: Activities for Daily Living (ADL); RCT: Randomized Controlled Trial; NLSH: Nordland Hospital Trust; EDSS: European Disability Status Scale; TIS-modNV: Trunk Impairment Scale- Mod Norwegian version; Mini-BesTEST: Mini Best Evaluation Systems Test; 10MWT: 10 Meter Walk Test; 12MWT: 2 Minute Walk Test; MSWS-12: MS Walking Scale-12; RVGA: Rivermead Visual Gait Assessment; MSIS-29: Multiple Sclerosis Impact Scale–29; MSQOL-54: Multiple Sclerosis Quality of Life–54; PGIC: Patient Global Impression of Change.

People with multiple sclerosis (MS) frequently present balance and walking disturbances [1], even when disability is minimal [2,3]. Dynamic stability of the trunk, commonly termed “core stability”, is one of the fundamental bases for balance and walking [4,5]. Core stability is found to be impaired in individuals with MS [6,7]. Effect of core stability training is limited and restricted to individual approaches [8-10]. Integration of core stability with other essential components of balance is requested [9] as balance is a major risk factor for falls [11,12]. Group-based training is considered motivating [13] and costeffective [14]. Group training is often an integral part of high-int ensity programs in specialist care. High-intensity programs are however rarely offered in municipalities. Group-based high-intensity core stability training is poorly investigated in terms of effects, user experiences and performance, and physiotherapists’ (PT)s’ opportunities for individualization, which is a prevailing principle in rehabilitation of people with MS [15].

A new individualized group-based physiotherapy intervention named GroupCoreSIT (S=stability, sensory stimulation, specificity; I= individualization, intensity; T= training, teaching) was developed to be tested in municipalities. Two preliminary studies on this intervention have been conducted with ambulant individuals with MS, one using a test-retest design [16] and one using Single Subject Experimental Design [17]. These studies provided support for the feasibility of the intervention, preliminary scientific evidence of short-term effect on balance, walking and activities for daily living (ADL) in ambulant individuals with MS and justification for a larger scale clinical trial.

The current GroupCoreSIT study consists of a prospective randomized controlled trial (RCT) and a qualitative study. The study provides several additional elements than traditional core stability approaches. The intervention integrates individualization and group dynamics. Core activation, including all muscles in the trunk and attaching to the trunk [4], is combined with the following principles: optimal alignment of body parts and adaptation to base of support [5,18], coordination of proximal stability and distal movement [4,19], somatosensory stimulation of hands and feet [5,18,20], high-intensity [21], and teaching of self-management [15].

The theoretical framework of the GroupCoreSIT study is movement sciences [18] and neuroplasticity [20] integrated in an extended theoretical framework of phenomenology of the body [22-24] and enactive theories [25-30].

Study design

The GroupCoreSIT study consists of two related parts.

Part I: A prospective RCT will be conducted to evaluate the effects of the GroupCoreSIT on people with MS compared to standard care. The intervention will be offered for a period of 6 weeks, with a 6- month follow-up post-intervention.

Part II: A qualitative study will be conducted through: i) qualitative interviews with patients aimed to increase the knowledge about short and long-term experiences with GroupCoreSIT and standard care, with an endpoint of six months post-intervention, ii) observations and qualitative interviews with PTs aimed to analyze and identify essential aspects of physiotherapy performance and perceptions related to conduction of GroupCoreSIT particularly focusing on individualization, group dynamics and teaching patients selfmanagement in group settings, and iii) qualitative interviews with health personnel in hospital and municipalities focusing on deliberations regarding coordination of intensive physiotherapy in people with MS.

Study participants

To be eligible for enrolment, participants must have the following inclusion criteria: 1) definite diagnosis of MS, according to McDonald's criteria [31], 2) registered at the outpatient clinic at Nordland Hospital Trust, Bodø, Norway (NLSH), 3) living in one of six selected municipalities, 4) aged 18 years or more, 5) capable of providing signed written informed consent, and 6) scoring 1.0-6.5 on the European Disability Status Scale (EDSS) [32]. Exclusion criteria are: 1) pregnancy at enrollment, 2) exacerbation in the 2 weeks prior to enrollment, 3) and acute conditions affecting balance and walking.

Randomization

The participants are randomly assigned to the intervention group or to the control group in a 1:1 ratio (Figure 1). Randomization is performed by a web-based system developed and administered by the Unit of Applied Clinical Research, Institute of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway. Randomization is stratified according to the EDSS (1.0-3.5 vs. 4.0-6.5). The randomization takes place after the baseline assessment so that the health personnel are blinded to group allocation.

Figure 1: Flow chart study part I, the RCT.

Intervention

Six PTs with expertise in neurological physiotherapy will conduct the intervention in the selected municipalities. They will attend a 4-day practical and theoretical training on the intervention, with 1-2 followup videoconferencing sessions during the study.

After enrollment, and a few days before the group training starts, the PTs responsible to deliver the intervention conduct an individual assessment of each participant as a basis for individualization of the intervention. Each training group consists of three participants. The training sessions last for 60 minutes and will be performed three days per week, for six weeks. The PT instructs, demonstrates and uses hands-on facilitation to enhance performance with optimal quality of movement.

The intervention includes 32 standardized exercises, which will be performed in various postural sets (Table 1). These exercises are organized in five “blocks” according to their objectives, named and described (Tables 2-6). Each exercise includes five levels of difficulty to allow tailoring of the intervention. In the group sessions, all participants do the same exercise simultaneously, but may perform it on various levels.

Table 1: Descriptions of various postural sets “optimal alignment”.

Table 2: Exercises that aim for core activation simultaneously with sensory-motor activation of the foot or hands to enhance adaptation to base of support. There were five different variations in each exercise (only one example is given here).

Table 3: Exercises for optimal adaptation to the base of support and activation of the core while enhancing concentric and eccentric activity in muscles in neck, upper and lower limbs. There are five different variations in each exercise (only one example is given here).

Table 4: Exercises that target optimal adaptation to the base of support and core activation while selectively moving arms and legs or particular parts of the core. Focus on dynamic stability, keeping one part of the body stable while moving another. There were five different variations in each exercise (only one example is given here).

Table 5: Exercises targeting optimal adjustment to the base of support and activation of the core while recruiting larger muscle-groups in various standing positions, challenging postural control and balance. There were five different variations in each exercise (only one example is given here).

Table 6: Exercises that target optimal adjustment to the base of support and activation of the core while systematically performing contraction/relaxation of other parts of the body.

The intervention emphasizes performance of exercises with optimal alignment in various body parts to enhance recovery as opposed to compensatory strategies [5]. Dynamical proximal stability is enhanced by using a therapeutic ball, either keeping the ball still against a wall (using the trunk muscles) while moving the arms or legs, or moving the ball while transferring weight from side to side or up/down (using the trunk muscles) keeping hands and/or feet stable.

Sensory stimulation of hands and feet to update body schemas is facilitated by using a massage ball or roller [5,18].

Dual tasks are integrated as variations, for example by singing while exercising. Proprioception is enhanced by performing exercises with closed eyes. Ball activities such as bouncing are included to enhance group dynamics.

Every session starts with sharing the participants´ experiences between sessions, followed by exploring their own standing balance on two legs and/or single leg standing, and then they conduct at least one exercise from each “block”. Up to ten repetitions for each exercise with good quality of movement are performed, fewer if quality deteriorates. Each session ends with active relaxation and re-exploring balance. The participants are recommended to perform 30-minute of unsupervised home exercises, optionally divided into smaller intervals, two times per week. Home training is recorded in a training diary.

The participants in the control group receive standard care, i.e. following their ordinary physiotherapy services and/or routines/ activities. These activities are recorded in a diary.

Outcome measurements

We hypothesized that high-intensity individualized group-based core stability training performed at the municipal PTs’ facilities will improve balance, walking, ADL, physical activity, and quality of life. This is reflected in the primary and secondary outcomes presented below (Table 7).

Table 7: Overview of primary and secondary outcomes.

Recruitment and study procedures

Enrollment of participants takes place at the outpatient clinic for people with MS at NLSH. The administration at the clinic sends written information on the study to patients with MS fulfilling the inclusion criteria and living in the selected municipalities. Informed consent forms are returned by mail to the MS-nurse at the NLSH’s outpatient clinic and delivered to the project leader. The date for the baseline visit is then arranged.

At enrollment, a neurologist performs the EDSS screening and records medical history and other baseline data including type of MS, EDSS, age, gender, weight, height, medications, physiotherapy and other health services during the previous 6 months. An independent appropriately trained PT blinded to group allocation performs a standardized assessment for all the participants using valid and reliable assessment tools (Table 7).

At 1 week, 3-month and 6-month post-intervention all the participants undergo the same standardized assessment performed at baseline by the assessor blinded PT (Table 8).

Table 8: Overview of data collected.

Exercise, activity and disease monitoring

On a weekly basis during the intervention period all the participants record: changes in medication, general wellbeing (qualitative selfscore), exacerbations, and physical activities using a diary with a ticketbox. In addition, participants in the intervention group only will record: degree of exhaustion following group sessions and home exercise completion using the Borg Exertion Scale [45].

Statistical methods

An intention-to-treat analysis will be performed on all randomized subjects and will serve as the primary analysis for all outcomes in this study. The data analysis will be carried out using IBM SPSS Statistics. Possible differences between the groups at baseline will be calculated by using independent sample t-test for continuous variables and chisquare for categorical variables. Primary outcomes, changes in balance in sitting and standing/walking between the groups will be calculated by using independent sample t-test as will secondary outcomes. Differences over time between groups will be investigated by using linear mixed methods, given that the data is normal distributed.

Sample size calculation

The sample size calculation for this study was based on data from the pilot study investigating the effectiveness of GroupCoreSIT on balance, walking and ADL in a similar sample of people with MS using the TIS-modNV [16] and additionally on the Mini-BESTest [35]. A difference of 0.75 SD on the Mini-BESTest between the intervention and the control group was considered as clinically significant. Fifty-six individuals with MS in each group were required to have an 80% chance to detect a 0.75 SD difference between the groups with a significance level of 0.05 (alpha) on two-sided tests. Assuming a 30% dropout, we aimed to recruit 72 persons with MS, i.e., 36 in each group for part one of the study.

Design, participants and recruitment

The qualitative study has an exploratory design, and is based on three strategic samples that will be consecutively invited to participate: i) a subset of 24 participants in the clinical trial, 12 from each group, ii) the six PTs conducting the intervention, and iii) 16-20 health professionals involved in health services to individuals with MS (Figure 2).

Figure 2: Study part II; the qualitative study.

Patients’ experiences: Patients’ perceptions of the intervention and standard care will be examined through qualitative research interviews [46]. The interviews will be conducted twice, at the end of intervention and 6 months post-intervention. Purposive sampling will be performed to obtain variation in training groups, EDSS, age, gender and time since diagnosis. Participants from the intervention group will be asked about the first assessment/consultation, the group situation, content and amount of training, pros and cons, home exercises and ADL. The same number of participants from the control group will be interviewed regarding their experiences with standard care, investigating the same topics. The scope of the second interviews is to investigate retrospective reflections regarding wellbeing and coping with ADL before, during and after the intervention period, selfmanagement, and continuity of care, pros and cons. The material will be transcribed and analyzed using Systematic Text Condensation [46] applying phenomenology of the body [22,23], enactive theory [25-29] complemented by neurosciences [20] as a theoretical framework.

Physiotherapists performance of intervention and reflections: Observation and videotaping of the assessment of one patient in each training group (12 observations) will be conducted to investigate what the PTs emphasize in their individual assessment prior to the first group session. These observations will be complemented by qualitative research interview with the actual PT (12 interviews) to explore the PTs’ perceptions regarding the assessment, planning of the group sessions, choices of exercises and individual goals. One session in each group will be observed and videotaped (12 observations) to investigate how the PTs tailor the intervention in situ and how they act and interact with the participants. The PTs will be interviewed at the end of each training group period (12 interviews) to illuminate the PTs’ perceptions regarding education in the intervention and experiences from conducting it, particularly focusing on goal attainment, individualization in a group setting and home exercises. The material will be transcribed and analyzed using Systematic Text Condensation [46] applying phenomenology of the body [22,23], enactive theory [25-30] complemented by neurosciences [20] and practice knowledge [47-49] as a theoretical framework.

Coordination of care and intensive physiotherapy: Qualitative interviews with health professionals will be conducted to explore coordination of care between the outpatient clinics for people with MS and the municipalities regarding high intensity physiotherapy. Eighteen health professionals (MS-nurses, neurologists, PTs) at the hospitals’ outpatient clinics and 8-10 health professionals in municipalities (general practitioners, PTs) will be interviewed before the intervention (for standard care) and after the RCT. The material will be transcribed and analyzed using Systematic Text Condensation [46] applying guidelines for health coordination [15,50] as analytical tools.

The current study aims to investigate the effects of a tailored physiotherapy program designed for individuals with MS to improve balance, walking, ADL, physical activity and health-related quality of life. The intervention is based on current theoretical frameworks and includes individualization, group dynamics and self-management. The intervention was designed for implementation in a municipality setting, but may be also suitable for specialist health care settings. The conduction of the GroupCoreSIT study will provide evidence on whether a six-week group-based, individualized high-intensity physiotherapy program for ambulant individuals with MS improves balance and walking, ADL, physical activity, and quality of life compared to standard care.

The study will also provide insight into persons with MS’ perceptions regarding the intervention and standard care, knowledge about performance of individualized group intervention, and coordination of intensive physiotherapy programs for these people.

The study is pragmatic in nature, has both qualitative and quantitative elements; hence the intention is that the conclusions drawn from the data generated will be directly transferable to clinical practice. Policy makers and therapists implementing physiotherapy programs will benefit from the results of the study, by an enhanced evidence base in this area.

Patient recruitment commenced in September 2015 and ended in January 2016.

The study is restricted to patients who have volunteered and provided written informed consent in accordance with the Declaration of Helsinki. The trial and the qualitative study received approval from the Regional Committee for Medical and Health Research Ethics in Norway (REK South-East: 2014/1715-7).

Consent for publication of data that is analyzed on a group level is obtained from all participants. Publication of videos or any other material relating to individual participants is not applicable for publication.

The data supporting the results of this study will be available upon request.

This study was funded by the Northern Norway Regional Health Authority (Project Grant 1240) and the UiT, the Arctic University of Norway.

We thank Professor Tom Wilsgaard, UiT, the Arctic University of Norway for assistance in sample seize calculations.