Adapted functional training versus Mat Pilates in motor and non-motor symptoms of individuals with Parkinson's disease: study protocol for a randomized controlled clinical trial Functional training versus Mat Pilates in Parkinson's disease

Background: Motor and non-motor symptoms affect the life of those living with Parkinson's disease, and it is clear that exercise offers benets in these aspects. However, the effects of adapted functional training interventions and the Mat Pilates as a form of rehabilitation for the disease in question have not yet been established. Thus, this study aims to propose an adapted functional training protocol and Mat Pilates for individuals with Parkinson's disease and to evaluate the effects on motor symptoms (balance, cardiorespiratory tness, lower and upper limb strength, exibility and agility), as well as , in non-motor symptoms (cognition, depressive symptoms, mood state, anxiety and nitude) by means of a randomized controlled trial. Methods: Protocol for a randomized clinical trial in which 45 individuals with Parkinson's disease will be recruited and randomly allocated to one of three groups: (1) functional training; (2) Mat Pilates; (3) control group. Both intervention groups will have 60-minute classes twice a week for 12 weeks. The primary outcome will be analyzed by balancing with the Mini-BESTest test. Secondary outcomes will include cognition, aging perspective, mood, anxiety, depression, mobility, muscle strength, handgrip strength, exibility, range of motion, and cardiorespiratory tness. The evaluations will be performed in the pre-intervention period (baseline), after 12 weeks of intervention, after 3 months, 6 months and 1 year of intervention. Discussion: This will be the rst randomized trial to compare the effects of functional training and Mat Pilates in a population with Parkinson's disease. It is hypothesized that improvements in motor and non-motor symptoms will be greater and more lasting after functional training and Mat Pilates interventions than those that maintain their routine activities, given the benets of exercise and the unprecedented protocols in this disease.


Study design
A 12-week randomized clinical trial will be conducted to determine the effect of two exercise interventions on motor and non-motor symptoms in individuals with PD. The objectives will be to investigate the effect of a structured program of adapted functional training and a structured Mat Pilates program on motor (balance, cardiorespiratory tness, lower and upper limb strength, exibility and agility) and non-motor (cognition, depression, mood anxiety and nitude) in individuals with PD. The study will consist of three groups; Control Group (CG); Functional Training Group (FTR) and Pilates Group (PG). Ethical approval was granted through the Ethics Committee on Research in Human Beings (CEPSH) of UDESC -protocol 3.613.483 and registered with the Brazilian Registry of Clinical Trials (ReBEC) (RBR-6ckggn). All procedures followed the Helsinki declaration. Figure 1 shows the Consolidated Standards of Reporting Trials (CONSORT) owchart, enrollment schedule, interventions, and study evaluations. Additional le 1 shows the checklist using the SPIRIT used in the study (appendix).

Participants
Individuals of both sexes diagnosed with idiopathic PD, recruited in the city of Florianópolis and São José (Santa Catarina, Brazil), through the Santa Catarina Parkinson's Association (APASC) and newspaper, university website and e-mail disclosures invited to be part of the study. The individuals who will participate in the research will be included in the Rhythm and Movement Program and BPaRkI -Brazilian Parkinson's Rehabilitation Initiative, and the classes will take place at the Health and Sports Science Center of Santa Catarina State University (UDESC).

Inclusion and exclusion criteria
Inclusion criteria include: (1) clinical diagnosis of PD following UK brain bank criteria [18]; (2) both sexes; (3) age greater than or equal to 50 years; (4) with stable doses and no change in antiparkinsonian medication within two weeks; (5) stage I to IV classi ed by Hoehn and Yahr; (6) data collection in the "on" phase; (7) without practicing any exercise program for at least two months. The study exclusion criteria include: (1) do not reach MMSE cutoff [19]; (2) classi ed in stage 5 PD (wheelchair users) [20]; (3) do not complete all stages of the study; (4) perform combined practice of any physical exercises; (5) who are not stable on medication doses; (6) not present in up to 75% of classes.

Sample size calculation
The sample size calculation was performed using the G * Power 3.1.9.228 software, based on the study's primary outcome, the balance, assuming a moderate effect based on similar interventions, according to Cohen with 0.37 effect size, signi cance level of 5%, 95% test power and 20% sample loss. Thus, 15 individuals will be assigned to each group (FTG, PG and CG) according to the sample calculation, in a total of 45 participants.

Randomization and Blinding
Upon consent of the study, survey participants will be randomly assigned to FTG, PG and CG. The randomization process will be done through the program randomization.org, which will predict the allocation of individuals in the three groups. Two trained evaluators will be blind to group allocation and will not participate in the intervention. All individual information will be stored in an unidenti able form.
In this study it is not possible to blind participants from their assigned experimental groups, because the exercises of each intervention they perform will reveal their allocation to a particular group.

Intervention
Adapted functional training Functional training classes will be held at the Health and Sports Science Center (CEFID) of the Santa Catarina State University (UDESC) in Florianópolis -SC, in a large gym with adequate facilities.
Individuals assigned to this group will participate in a functional training program adapted for PD for 12 weeks. Each class will last 60 minutes and will be held twice a week in the afternoon. Individuals will need to complete at least 75% of the prescribed classes. This exercise modality was chosen because it is appropriate for individuals with PD who may have limited physical capacity. This exercise program will promote improvement in lower and upper body movements, as well as stimulate balance, cardiorespiratory tness, lower and upper limb strength, exibility and agility, as well as motor coordination. In addition, functional training may promote psychological bene ts, such as improved cognition, depressive symptoms, mood, anxiety and nitude, among other possibilities.
Lessons will be divided into: warming up (15 minutes) focused on joint warm-up with walking, moving and running, and encompassing broad-to-speci c joint movements, including exion, extension, abduction, adduction and rotation, initiated by the upper body until reaching the lower limbs. The main part (40 minutes) that will stimulate the evolution of speci c functional training exercises, including upper limb, trunk and lower limb muscle strength, such as squats, advances, sitting and rising, abductions, adductions, extensions and exions in addition to focusing on the activation of the abdomen muscles, as well as trunk exions, extensions and rotations. Also, exercises that enhance exibility, endurance, power, balance, coordination, agility and strength are the standard exercises of functional training.
Finally, stretching, slow walking, massage and myofascial releases (rest period) will be performed for 5 minutes to provide muscle relaxation. Both exercises will go from mild to vigorous intensities and with each week of intervention the degree of di culty of the exercises given will be greater, so that individuals have a progression over 12 weeks. In addition, music will be used according to the preference of participants during the classes as a motivational and playful factor. Detailed instructions for movements can be found in Table 1.

Mat Pilates
Mat Pilates classes will be held at the same venue, Center for Health and Sports Sciences (CEFID) of the Santa Catarina State University (UDESC) in Florianópolis -SC, in a large room suitable for the practice of the sport. Individuals assigned to this group will participate in a Mat Pilates program aimed at individuals with PD for 12 uninterrupted weeks. Each class will last 60 minutes and will be held twice a week in the afternoon. Individuals in this group will need to complete at least 75% of the prescribed classes. This modality was chosen by a system of exercises that integrate the body, mind and provide strength, exibility, balance, body awareness, and postural control and seek physical and mental training that can improve the symptoms of the disease, although Pilates will promote improvement in depressive symptoms, anxiety, mood, cognition, among others.
The classes will be divided into: warm-up (15 minutes) in which will be explored the joint warm-up exercises, muscle activation and Mat Pilates movements, such as, breathing, imprint & release, hip release, spinal rotation, cat stretch, hip rolls, scapula isolation, arm circles, head nods e elevation & depression of scapula. The main part (40 minutes) with evolution of speci c movements of the Mat Pilates as breast stroke preparation (hand by hips), shell stretch, preparation abdomen, half roll back, roll up, single leg stretch, obliques, one leg circle, preparation shoulder bridge, hell squeeze prone, side kick, spine twist, among others included in the protocol. Relaxation will consist of self-stretching exercises using the ball and talk about each participant's perception of the classes for 5 minutes. Both exercises will go from moderate to vigorous intensities and with each week of intervention the degree of di culty of the exercises given will be greater, so that individuals have a progression over the 12 weeks. Music will be used during the classes according to the preference of the participants, to stimulate and encourage them in the proposed exercises. The details of the exercises that constitute the protocol are detailed in Table 2.
lates soil intervention protocol for individuals with Parkinson's disease. Page

Control Group
Participants assigned to the control group will be instructed to maintain their normal lifestyle and daily activities and not to engage in any other form of training during the 12 weeks. During this period, contact will be made by telephone every four weeks on the rst day of the month, at a time previously set by the researchers, as well as motivational guidance by telephone and lectures highlighting the importance of physical exercise and training care of your general health. In addition, they will be invited to attend classes after the intervention period.

Adverse Events
If any adverse events occur, they will be reported immediately to the principal investigator and, if appropriate, to the UDESC Human Research Ethics Committee (CEPSH). The principal investigator will be noti ed immediately of pressure drops, dizziness, chest pain, blurred vision, irregular pulse, fainting, and shortness of breath, falls or other adverse events.

Outcome Measures
All measurements will be performed in ve moments, namely the baseline period (T0) (pre-intervention), after the 12 weeks of intervention (T1) (post-intervention), and three follow-ups, three months after completion intervention (T2), six months after the intervention (T3) and one year after the intervention (T4). Measurements will be performed by three trained evaluators and all evaluators will be blinded to group allocation. Data collection, including the application of the questionnaire and physical tests, will take around 90 minutes at a time previously set by the researchers. A summary of all outcome measures that will be collected at each moment is shown in Figure 2 following SPIRIT.

Primary outcome assessment
Balance: The Mini-BESTest test, translated and validated in Brazil, is a 14-item test that focuses on dynamic balance, speci cally early transitions, postural responses, sensory orientation, and dynamic gait.
Its application takes 10 to 15 minutes and allows you to quickly and reliably track balance changes. Each item is scored from (0-2); A score of 0 indicates that a person is unable to perform the task while a score of 2 is normal. The best score is the maximum amount of points, being 28 [21].

Secondary outcome assessment
Demographic and clinical information: Regarding age, gender, marital status, educational level, occupation, presence of clinically diagnosed diseases, use of medications for PD, depression and anxiety, initial symptoms, date of diagnosis of PD, duration of illness, dominant body side, body side most affected by the disease and anthropometric measurements (BMI). Body mass index (BMI) classi cation was based on the WHO protocol (2016) [22], that is, thinness (BMI <18.5); eutrophy (BMI 18.5-24.9); overweight (BMI 25.0-29.9); pre-obesity and obesity (BMI> 30.0). Participants will be asked to report if there are any changes in medications during the study period. The UPDRS is a reliable (r-0.96) and valid scale.
Depression: Beck Depression Inventory (BDI), this is a self-report questionnaire originally developed by Beck et al. (1961) [23]. It contains 21 objective multiple-choice questions related to depressive symptoms such as hopelessness, irritation, cognition, guilt and feelings of punishment, as well as physical symptoms such as fatigue, weight loss and sexual interest. The sum of individual item scores gives a total score, where the highest score is 63, which indicates a high degree of depressive symptoms and the lowest score is zero, which corresponds to the absence of depressive symptoms [23].
Anxiety: Beck Anxiety Inventory (BAI), this inventory was translated and validated in Brazil. It consists of 21 self-reported questions that highlight somatic, affective, and cognitive signs of anxiety symptoms.
The total score is 63 points and indicate a high degree of anxiety [24].
Mood: Brunel's Mood Scale (BRUMS) assesses six mood states (tension, depression, anger, vigor, fatigue, and mental confusion). The questionnaire consists of 24 ve-level scales, which must be answered by the participant considering how he feels at the moment of the evaluation. By summing up the answers for each aspect, a score ranging from 0 to 16 for each mood state is obtained. BRUMS has been validated for Brazil, with internal consistency values (Cronbach's alpha) greater than 0.70 for all aspects [25].
Aging Perspective: Sheppard Inventory adapted to Portuguese and validated by Neri (1991) [26]. The instrument consists of 20 questions divided into 4 subgroups, which allow to evaluate the respondent's opinion regarding: a) possibility of being happy in old age; b) if old age foreshadows dependency, death and loneliness; c) if it is better to die early than to feel anguish and the loneliness of old age; d) if old age can provide feelings of integrity. Initially, by means of scores, it is possible to determine whether participants have a positive or negative perception of nitude (prevalence) [26].
Cardiorespiratory tness: Ergospirometry will be used to conduct the submaximal stress test where you will assess cardiorespiratory tness, indicated for populations with Parkinson's disease [27]. Exhaled gases and ow volume will be collected during the test and analyzed by calibrated metabolic system (Quark CPET Ergo, Cosmed, Rome, Italy) to provide oxygen absorption measurements. The test will be terminated at the predetermined value.
Range of motion: To assess shoulder range of motion, the digital goniometer (Absolute Axis 360 °) will be used for shoulder exion and abduction movements [28]. The abduction movement will be performed with the individual sitting, and the exion movements with the same in the supine position.
Flexibility: For the lower limb exibility test the Sit and Reach test will be used. The test begins with the individual sitting in a chair, one leg should be knee bent approximately 90° and the foot at on the oor; the other leg should be extended. The measurement will be the distance between the middle toes and the tiptoe, being considered negative anterior to the tiptoe and positive the distance that the toes pass from the tiptoe [29].
Hand Grip Force: Will be measured with a hydraulic dynamometer, adjusted in the second position, due to hand size, measuring the force produced by an isometric contraction recorded in kilograms or pounds.
The subject will be asked to sit in a chair without upper limb support, but with the back supported, shoulder addicted, elbow exed at 90 °, forearm in neutral position and wrist ranging from 0 ° to 30 ° in length and between zero and 15 ° ulnar deviation [30].
Muscle strength: Biodex System 4 PRO isokinetic dynamometer (BiodexTM Medical Systems Inc., Shirley, NY), used with individuals with Parkinson's disease [31], will be used to measure lower limb muscle strength. The isokinetic strength protocol will involve the knee extensors and exors with the dominant limb, the range of motion will vary from 0 ° to 90 °.
Mobility: Timed Up & Go (TUG) is a screening tool commonly used for fall hazards in the elderly. Translated and validated in Brazil, its main objective is to evaluate mobility. TUG measures the time it takes for an individual to perform some functional maneuvers, such as getting up, walking, walking, and sitting down [32].

Statistical analysis
The data will be tabulated in the Microsoft Excel® program and transferred to the statistical package SPSS -IBM version 20.0. Descriptive statistics (mean, standard deviation and percentage) will be performed, followed by the two-way ANOVA with repeated measures and Sydak comparison test for comparative analysis of group results and pre and post-group comparisons in the three groups. Post hoc analysis using Bonferroni correction will be applied as appropriate. All subjects will be analyzed in the primary intention-to-treat analysis and protocol analysis will also be performed including all participants who have at least 75% compliance with the exercise. Signi cance level adopted of 5%.

Discussion
This protocol for randomized clinical trial aims to provide a program and exercise with two distinct modalities, functional training and the Mat Pilates. In order to provide an answer as to which of these may bring major improvements in motor symptoms (balance, cardiorespiratory tness, lower and upper limb strength, exibility and agility) and non-motor symptoms (cognition, depressive symptoms, mood state, anxiety and nitude) in individuals with PD, positively in uencing future non-pharmacological treatment approaches in these individuals.
The literature has bene ts of functional training and the Mat Pilates as a non-pharmacological treatment, but there is still little evidence and non-randomized experimental studies. Functional training is an integrated and multiarticular exercise modality that according to Horne et al. (2019) [16] and Leal et al.
(2019) [10] promotes improvement in muscle strength, 6-minute walk test distance, motor function, quality of life, anxiety and depression in individuals with PD. The Mat Pilates can prevent the aggravation of a series of symptoms, both in motor and non-motor aspects, which make life di cult for these individuals and can be a great ally to the well-being of body and mind to maintain independence reintegration into society [17].
Furthermore, although pharmacological treatments seek to reduce the impact of some motor symptoms, they signi cantly decrease the quality of life of individuals living with PD [33]. Currently, the focus on investigations of different non-pharmacological interventions has increased due to side effects caused by medications such as bradykinesia and gait freezing [34]. Therefore, the importance of combining medication and concomitant physical exercise [35]. Thus, this will be the rst randomized controlled trial designed with the bene ts of functional training and the Mat Pilates in the non-pharmacological treatment of PD. This will help to identify the e cacy of both in the motor and non-motor symptoms of the disease, besides being safe and economical approaches for this population, thus being a pioneer study when it comes to the comparison between these two modalities.
Thus, it is considered that the implementation of a functional training protocol, as well as the Mat Pilates for individuals with PD may contribute to form a parameter on which professionals can be based on the The results derived from this project will be published in international scienti c journals. The data can be made available with the corresponding author upon request.  Study evaluation schedule (SPIRIT).

Supplementary Files
This is a list of supplementary les associated with this preprint. Click to download. SPIRITchecklist.doc