Clinical trial NCT04011579: Pilates Training in Multiple Sclerosis
Official title: Multiple Sclerosis Fitness Intervention Training With Pilates Exercises
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Multiple Sclerosis
Physical Activity
Keywords: Physical activity
Pilates
Fitness
Lead sponsor: Fondazione Italiana Sclerosi Multipla
Sponsor class: OTHER
First posted: 2019-07-08
Enrollment: 126
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: To date, despite recent advances in MS care including rehabilitation interventions, many PwMS are unable to access these developments due to limited mobility, fatigue and related issues, and costs associated with travel.

Thus, physical activity at home could be a new way to deliver exercises to the patients. Although Pilates did not show any significant advantage over standardized physical therapy in the current literature, it is a good method to promote physical activity, sensorimotor integration and cognitive stimulation. Thus, it could be a treatment option to improve fatigue, balance and walking abilities in PwMS; consequently, Pilates could be suggested by the clinician as a physical activity to be integrated in the daily life.

This possibility could be made more feasible using new tools such as those offered by low cost devices.

The main MS-FIT project purposes are to provide and to test a tool based on serious game concept of Pilates-inspired exercises for daily use at home, by mixing the entertainment aspects typical of the videogames and the possibility to perform physical activity.

The MS-FIT tool does not pursue therapeutic aims as rehabilitation does, but it could have a positive impact on prevention and health in MS.

MS-FIT, by using the Microsoft Kinect Motion Controller Xbox or similar to deliver adapted physical activity, offers the possibility to transform the Pilates exercises into a virtual reality game.

MS-FIT, through a multicentre approach, would provide:

* a feasibility study in order to:

  * refine the tool for the final customized version to be used in a RCT MS study
  * assess the tool for PwMS in terms of technology acceptability and satisfaction-to-use
  * assess the process of recruitment, the adherence to the intervention, the dropout rate and identify potential issues
  * assess human resources necessary for the RCT
  * estimate the effect of the intervention and its variance necessary to calculate the appropriate sample size for the RCT
* a RCT study in order to evaluate the effect of a physical activity intervention of exercises inspired to Pilates self-managed at home in terms on PwMS

Detailed description: Devices and technologies for at-home interventions could provide to PwMS with mild disability useful tools to successfully maintain own physical, cognitive and emotional status by performing at-home physical activity/exercises and avoiding outpatient interventions. Together, new devices and technologies could help in overcoming all barriers (i.e. transportations, working time, etc.) hindering the adherence to and, consequently, efficacy of the outpatient treatments.

Although Pilates did not show any significant advantage over standardized physical therapy in the current literature, it is a good method to promote physical activity, sensorimotor integration and cognitive stimulation. Thus, it could be a treatment option to improve fatigue, balance and walking abilities in PwMS; consequently, Pilates could be suggested by the clinician as a physical activity to be integrated in the daily life.

This possibility could be made more feasible using new tools such as those offered by low cost devices.

The main MS-FIT project purposes are to provide and to test a tool based on serious game concept of Pilates-inspired exercises for daily use at home, by mixing the entertainment aspects typical of the videogames and the possibility to perform physical activity.

The MS-FIT tool does not pursue therapeutic aims as rehabilitation does, but it could have a positive impact on prevention and health in MS.

MS-FIT, by using the Microsoft Kinect Motion Controller Xbox or similar to deliver adapted physical activity, offers the possibility to transform the Pilates exercises into a virtual reality game.

MS-FIT, through a multicentre approach, would provide:

* Feasibility study
* RCT study

All the 14 participating centres will select a dedicated therapist who will be responsible for patient training in using the MS-FIT tool.

All the subjects recruited following the inclusion/exclusion criteria will sign an informed consent and all the procedures (feasibility and RCT) will be in agreement with the Declaration of Helsinki (1964) and approved by Local Ethical Committee.

No trial-specific procedures will be conducted before informed consent has been obtained, and participants will be reminded that they may withdraw from the trial at any time without it affecting the quality of their care in the future.

Participants with relapses during the period of their involvement in the project will be considered as drop out and will be considered in the analysis for the entire period of study participation.

Feasibility study

Primary objective:

• the refinement of the tool for the final customized version to be used in a RCT MS study. The primary objective will be reached by fixing eventual bugs relieved during the feasibility study and taking into account results from the assessment in terms of technology acceptability and satisfaction-to-use, adherence to the intervention, intervention safety and the physical effects of the intervention.

Secondary Objectives:

* the estimation of human resources necessary for the RCT.
* the estimation of the effect of the intervention and its variance necessary to calculate the appropriate sample size for the RCT.

Due to the nature of the feasibility study and based on previous literature showing that a sample size of 25-40 subjects per arm is adequate for a feasibility trial, the investigators will recruit 28 PwMS per arm. All the 14 participating centres will recruit a total of 56 recruited patients following the inclusion and exclusion criteria. In the range of EDSS inclusion criteria 28 subjects will be recruited with lower disability (EDSS 2-3) and 28 with higher disability (EDSS of 3.5 or 4). For both levels the subjects will be randomized into two groups: MSFITFeas (MS-FIT at-home + "unspecific physical activities") and CTRLFeas ("unspecific physical activities"). Randomization will be provided by an independent randomization service at FISM accessed via a web-based system, using computer-based block randomization (1 factor: EDSS score 2-3 and 3.5-4). Patient will be allocated to MSFITFeas and CTRLFeas in a 1:1 ratio. Confirmation emails will be sent to Centres PI.

The MSFITFeas group will self-manage MS-FIT at-home for 6 weeks, performing at least 3 sessions/week for a total of 30 minutes of exercises (also distributed during the day with a minimum slot of 10 minutes) for each session. During this period Xbox One and Microsoft Kinect 2.0 will be delivered to the participants for the aims of the study. Before starting the at-home intervention each subject will be trained to the use of the platform by a therapist. No rehabilitative interventions except sphincter and speech rehabilitation and psychological support, are admitted for the 6 weeks of participation to the project. The execution of unspecific physical activities, if not already practiced, will be suggested to the participants. For the 6 weeks of participation to the project CTRLFeas will be similar to MSFITFeas group except for the execution of MS-FIT at-home.

The protocol for the Feasibility study will consist on (Figure 2):

* T0 evaluation (PRE)
* 6 weeks of intervention

  * MSFITFeas: unspecific physical activities + MS-FIT at-home
  * CTRLFeas: unspecific physical activities
* T1 evaluation (POST)

The evaluation for the Feasibility study are described in the section Outcome Measures.

Deliverables Deliverables of the Feasibility study will be the final customized tool, a set of indications for the management of the RCT, the sample size estimation for the RCT.

Focus group A nested qualitative study on 14 participants will explore patients' experiences of MS-FIT via Focus Group Meeting (FGM). The objectives are to provide insight into the quantitative results, explore strengths and limitations of the intervention with MS-FIT, so as to guide the RCT.

The report of each FGM analysis will be submitted to FGM participants for review (respondent validation).

Deliverables Deliverables of the nested qualitative study will be the delivery of the report of the FGM analysis.

RCT study

Primary Objective:

• evaluation of the change in TUG.

Secondary Objectives:

* evaluation of the physical effects also in terms of self-reported outcome, upper limb performances, resistance in walking and physical activity, cognitive and psychosocial effects, quality of life and wellbeing. Differences in physical and cognitive performances due to the genetic features will be evaluated also considering subgroups identified through the polymorphism analysis.
* evaluation of the acceptability and satisfaction-to-use, adherence to the intervention, intervention safety through the measurements of endpoint already listed for the Feasibility study.

The RCT sample size will be definitively calculated based on the results from the feasibility study. However, by considering the literature about Pilates in MS, the investigators can preliminary estimate the needed sample size. In particular, the investigators refer to the TUG post-intervention improvement found by Karlon et al. in a group of PwMS performing Pilates. For our aim, the investigators can consider this result even if no differences between Pilates group and control group (Physiotherapy) were found. Pilates group improved the performance in TUG of about 1.8s, that could be considered as clinically relevant for PwMS. By considering a variability of about 3.4s, a power of 80%, a level of significance (two sided) of 5% and a potential loss of 15% of patients at follow-up, the estimation of the necessary sample size consists of approximately 63 subjects for the experimental group (a total of 126).

All the 14 participating centres will be involved in the patients' enrolment. The subjects will be randomized into two groups: MSFITRCT (MS-FIT at-home + "unspecific physical activities") and CTRLRCT ("unspecific physical activities"). The randomization will be carried out using a web based procedure and will be centrally managed. A stratified minimization/adaptive algorithm will be used in order to balance the baseline EDSS (2-3 vs 3.5-4) factors across the two groups.

The MSFITRCT group will self-manage MS-FIT at-home for 12 weeks, performing at least 3 sessions/week for a total of 30 minutes of exercises (also distributed during the day with a minimum slot of 10 minutes) for each session. During this period Xbox One and Microsoft Kinect 2.0 will be delivered to the participants for the aims of the study. Before starting the at-home intervention each subject will be trained to the use of the platform by a therapist. The follow-up (FU) evaluation will be after 6 weeks since the end of the intervention. No rehabilitative interventions except sphincter and speech rehabilitation and psychological support, are admitted for the 18 (12 + 6) weeks of participation to the project. The execution of unspecific physical activities, if not already practiced, will be suggested to the participants. For the 18 (12 + 6) weeks of participation to the project CTRLFeas will be similar to MSFITFeas group except for the execution of MS-FIT at-home.

At the end of the 18 weeks, the participants of the CTRLRCT group will be offered the MS-FIT intervention.

The requirement that the enrolled patients will have not to perform any supervised physical activity or rehabilitative intervention is in line with recent studies showing that most of PwMS with mild disability (78.34% EDSS \<4) were not treated with rehabilitation.

The subjects involved in the feasibility study will be excluded from the RCT study in order to avoid bias effects.

The protocol design for the RCT study will consist on (Figure 3):

* T0 evaluation (PRE)
* 12 weeks of intervention

  * MSFITRCT: unspecific physical activities + MS-FIT at-home
  * CTRLRCT: unspecific physical activities
* T1 evaluation (POST)
* T2 evaluation (FU) - after 6 weeks from T1

The evaluation for the RCT study are described in the section Outcome Measures. Moreover, blood samples will be collected at T0 to investigate if genetic polymorphisms of candidate regulators of neuronal plasticity could be correlated to the response to the proposed protocol. According to previous report MS subjects of the two RCT groups could be subdivided in subgroups with respect to the polymorphism features. For example, for the CNR1 gene the subdivision could be based on the number of AAT repetitions (short AAT: homozygous or heterozygous for allele with ≤11 repeats of AAT triplets; long AAT: homozygous for allele with ≥12 repeats of AAT triplets).

Differences among subgroups in terms of physical and cognitive performances will be evaluated.

In particular, all patients will be genotyped for a total of 55 genetic polymorphisms of 23 potential regulators, like: Homer1; AKT1; RAPTOR; D2R; GAPD; CHAT; p53; BRCA2; LIG4; XRCC5; CYP3A4; NBS1; MDM2; CNR1, ATTn; CNR2; GRIN1; GRIN2B; TRPV1; FAAH, COMPT; (Brain-derived neurotrophic factor) BDNF.

Blood sample will be assessed from participants early in the morning after awakening (8h). To synchronize the sample for lifestyle variables, subjects were requested to avoid excessive physical activity the last three days before the blood sampling, sleep for 7-8h the night before study, avoid starving, and eat a usual breakfast in the morning (approximately 1h before the time of the breakfast).

The samples will be collected by each participant centre and shipped to the IRCCS Neuromed, Pozzilli, Isernia (Prof. Diego Centonze) for the analyses.

Deliverables Deliverables will be the report of the results of the trial and the final guidelines to make available and easy-to-use the MS-FIT tool

Criteria for Premature Withdrawal

Criteria for the premature withdrawal are:

1. Patients withdrawal of the consent anytime;
2. Any medical conditions that the investigator determines jeopardize the patient's safety if she/he continues the study and/or study results;
3. Patient's no-compliance to complete the study procedures
4. MS Treatment changes during the study

Eligibility criteria: Inclusion Criteria:

* All disease courses of MS
* Expanded Disability Status Scale (EDSS) 2-4
* Hospital Anxiety and Depression Scale (HADS) \< 10 in the two subset of anxiety and depression
* Berg Balance Scale (BBS) \> 46
* Mini-Mental State Examination (MMSE) \> 24
* At least 1 month without having been treated with rehabilitation
* Willingness to sign informed consent

Exclusion Criteria:

* Visual deficits that could compromise the use of MS-FIT
* Relapses in the last 3 months

Primary outcomes:
measure: Change in Timed Up & Go (TUG)
timeFrame: T0: before intervention; T1: after 12 weeks of intervention; T2: 6 weeks after T1
Secondary outcomes:
measure: Change in Timed 25-Foot Walk (T25FW)
timeFrame: T0: before intervention; T1: after 12 weeks of intervention; T2: 6 weeks after T1
measure: Change in Ambulation Index (AI)
timeFrame: T0: before intervention; T1: after 12 weeks of intervention; T2: 6 weeks after T1
measure: Change in 2-Minutes Walking Test (2WT)
timeFrame: T0: before intervention; T1: after 12 weeks of intervention; T2: 6 weeks after T1
measure: Change in Technology Acceptance Model (TAM)
timeFrame: T0: before intervention; T1: after 12 weeks of intervention; T2: 6 weeks after T1
measure: Change in Client Satisfaction Questionnaire-8 (CSQ-8)
timeFrame: T0: before intervention; T1: after 12 weeks of intervention; T2: 6 weeks after T1
measure: Change in Telehealth Satisfaction Scale (TeSS)
timeFrame: T0: before intervention; T1: after 12 weeks of intervention; T2: 6 weeks after T1
measure: Adherence to the intervention based on sessions
timeFrame: T1: after 12 weeks of intervention
measure: Adherence to the intervention based on drop-out
timeFrame: T1: after 12 weeks of intervention
measure: Change in Twelve Item MS Walking Scale (MSWS-12)
timeFrame: T0: before intervention; T1: after 12 weeks of intervention; T2: 6 weeks after T1
measure: Change in Visual Analogue Scale (VAS) (0-10) for balance performance
timeFrame: T0: before intervention; T1: after 12 weeks of intervention; T2: 6 weeks after T1
measure: Change in Nine-Hole Peg Test (9HPT)
timeFrame: T0: before intervention; T1: after 12 weeks of intervention; T2: 6 weeks after T1
measure: Change in Modified Fatigue Impact Scale (MFIS)
timeFrame: T0: before intervention; T1: after 12 weeks of intervention; T2: 6 weeks after T1
measure: Change in Brief International Cognitive Assessment for MS (BICAMS)
timeFrame: T0: before intervention; T1: after 12 weeks of intervention; T2: 6 weeks after T1
measure: Change in Patient Global Impression of Change (PGIC) with a 7-points scale
timeFrame: T1: after 12 weeks of intervention; T2: 6 weeks after T1
measure: Change in Multiple Sclerosis Quality of Life-54 (MSQoL54)
timeFrame: T0: before intervention; T1: after 12 weeks of intervention; T2: 6 weeks after T1
measure: Change in Psychological Well-Being Scales (PWB)
timeFrame: T0: before intervention; T1: after 12 weeks of intervention; T2: 6 weeks after T1
measure: Change in International Physical Activity Questionnaire (IPAQ)
timeFrame: T0: before intervention; T1: after 12 weeks of intervention; T2: 6 weeks after T1
measure: Change in Minnesota Leisure-Time Physical Activity Questionnaire
timeFrame: T0: before intervention; T1: after 12 weeks of intervention; T2: 6 weeks after T1
measure: Correlation between genetic polymorphisms and response to protocol
timeFrame: T0: before intervention
Other outcomes:
Locations:
city: Genoa
country: Italy
facility: Italian Multiple Sclerosis Foundation
Study officials:
affiliation: Italian Multiple Sclerosis Foundation
name: Giampaolo Brichetto
role: PRINCIPAL_INVESTIGATOR
References: