Transcranial direct current stimulation (tDCS) in addition to walking training on walking, mobility, and reduction of falls in Parkinson’s disease: study protocol for a randomized clinical trial

A prospective, randomized controlled trial with concealed allocation, blinded assessors, participants and therapists, and intention-to-treat analysis will be carried out (Fig. 1). Community-dwelling people with Parkinson’s disease will be recruited from the general community, by means of advertisements and by screening public rehabilitation services and lists of previous observational or cross-sectional research projects. Participants will be randomly allocated into either experimental group (i.e., walking training with tDCS) or control group (i.e., walking training with sham-tDCS). Outcome measures will be collected by trained researchers at baseline (week 0), at the end of the intervention (week 4), and 1 month beyond the intervention (week 8). Measurements and interventions will be conducted during the on phase of medication. Analyses of the inclusion criteria, getting the informed consent, data collection, and statistical analyses will be carried out by researchers, who will be blind to the group allocation. All the participants will be evaluated and receive all the information regarding the interventions in a research laboratory. The study obtained ethical approval from the Institutional Research Ethical Committee (CAAE 06952819.6.0000.5060) of the Universidade Federal do Espírito Santo, Vitória, Brazil. The trial was prospectively registered at the Ensaiosclinicos.​gov.​br, Registry: RBR-6bvnx6 (www.​ensaiosclinicos.​gov.​br/​rg/​RBR-6bvnx6/​).

Participants will be individuals with Parkinson’s disease, who will be eligible if they:

They will be excluded if they:

Therapists, who will deliver the intervention, will be eligible if they have received training from the research leaders (FZSA and LRN), who have more than 10 years of clinical experience in the area of neurological rehabilitation. A research assistant will be responsible for setting the stimulator on active or sham-tDCS, so therapists delivering the intervention will be blind to the group allocation.

Randomization will be computer-generated, by a researcher not involved in participant recruitment, and stratified according to the baseline walking speeds: slow (≤ 0.5 m/s) and intermediate (0.51 to 1.0 m/s) walkers, to ensure an even spread between the groups (1:1 allocation). The allocation of the participants will be concealed in sequentially numbered and sealed in opaque envelopes, prepared prior to the study by a research assistant, who will not be involved in the study. After the baseline measures have been collected, participants will be randomly assigned to the experimental or control group by the treating therapist, after revealing the content of the sealed opaque envelopes. All outcomes will be measured by blinded assessors. All enrolled participants will receive a code, in order to protect confidentiality before, during, and after the trial.

The experimental group will undertake a task-specific walking training associated with tDCS, 30 min per day, 3 days per week, over 4 weeks, i.e., 12 sessions of tDCS. A stimulator (DC-Stimulator Plus, NeuroConn, Ilmenau, Germany, or Neuroeletrics STARTIM tCS, Barcelona, Spain) will deliver a continuous direct current by a saline-soaked pair of surface sponge electrodes (size of electrodes 35 cm²). The anode will be placed at the Cz position on the scalp, corresponding to the location of the supplementary motor area, in accordance with the International EEG 10/20 system [15, 16]. The cathode will be positioned over the left supraorbital area. Participants will receive electrical stimulation of 2 mA, during the walking training. The 30-min sessions of task-specific walking training will include the practicing part of the task (about 10 min), where the muscles are working in a manner similar to a full task performance and practicing the whole task (about 20 min) [17]. Table 1 shows the ten walking activities of the task-specific walking training, which will be individually tailored for each participant.

The control group will undertake the task-specific walking training associated with a sham-tDCS. The control group will receive the same walking training, electrode positioning, and testing schedule as the experimental group. This will avoid bias related to the type and amount of attention given to the participants. If the addition of tDCS proves to be effective, the control group may receive the experimental training program after the experiment is complete.

The intervention will be undertaken in Clinics of Physiotherapy at the Universidade Federal do Espírito Santo. To encourage the participants to comply with the protocol, both groups will be asked to sign a symbolic contract of commitment to the proposed protocol. Participants will not be informed whether they are receiving tDCS or sham-tDCS.

The primary outcome is comfortable walking speed, measured by the 10-m Walk Test, and reported in m/s. The participants will be instructed to walk at their “comfortable speed” along a 14-m hallway, and the time to cover the central 10 m will be recorded with a digital stopwatch and converted to speed [18]. After a practice trial, the value obtained during a single test will be used for analysis [19].

Secondary outcomes are walking step length, walking cadence, walking confidence, mobility, freezing of gait, fear of falling, and falls.

Walking step length and cadence will be measured using the 10-m Walk Test. Step length will be calculated by dividing the covered distance, i.e., 10 m, by the number of steps to cover the distance, and reported in meters. Walking cadence will be calculated by dividing the number of steps by the time to cover the distance, i.e., 10 m, and reported in steps/min.

Walking confidence will be measured using the Brazilian version of the modified Gait Efficacy Scale and reported as scores ranging from 10 to 100. This scale is a 10-item measure that addresses the perception of the level of confidence in walking during challenging circumstances. The items include walking on a level surface and on grass, stepping over an obstacle, stepping up and down a curb, ascending and descending stairs (with and without a handrail), and walking over a long distance. The items are individually scored on a 10-point Likert scale, with 1 indicating “no confidence” and 10 indicating “complete confidence,” [20, 21].

Mobility will be measured by the Timed-up and Go Test (TUG) and reported as seconds. The participants will be seated in a chair with their backs against the chair back. On the command “go,” the participants will be instructed to rise from the chair, walk 3 m at a comfortable and safe pace, turn, walk back to the chair, and sit down. After a practice trial, the value obtained during a single test will be used for analysis [19, 22].

Freezing of gait will be measured using parts II and III of the New Freezing of Gait Questionnaire and reported as scores ranging from 0 to 28, where higher scores indicate worse episodes of freezing. The New Freezing of Gait Questionnaire is a reliable tool to detect and evaluate the impact and severity of freezing of gait, when applied to patients (ICC = 0.88) or caregivers (ICC = 0.97) [13].

Fear of falling will be measured using the Brazilian version of the Falls Efficacy Scale – International (FES-I Brazil) and reported as scores ranging from 16 to 64, where higher scores indicate greater fear of falling. The FES-I Brazil measures the fear of falling during 16 activities of daily living and has appropriate internal consistency (α = 0.93) and intra- and inter-examiner reliability (ICC = 0.84 and ICC = 0.91) [23].

The number of falls will be recorded by the use of a “falls diary” [24], and the proportion of fallers in each group will also be compared. All participants will receive weekly calendars on entry to the study, with instructions to record the following events: number of falls, visits by or to nursing and allied health personnel, and hospitalizations. Participants will be asked to return the completed calendar weekly to a researcher unaware of the group allocation.

An independent researcher, who will be blind to the group allocations, will monitor any adverse effects and perform database management and statistical analyses. The treating therapists will be responsible for the monitoring of doses and compliance.

Twenty-four participants will be recruited, with walking speed as the primary outcome. The sample size has been calculated, to reliably detect a between-group difference of 0.18 m/s in walking speed, with 80% power, at a two-tailed significance level of 0.05. In previous trials [9, 16, 25] with similar samples of community-dwelling people with Parkinson’s disease who received tDCS associated with walking training, the mean walking speed of the participants was 0.73 m/s (SD 0.15 m/s), measured by a timed-walking measure. The least number of participants needed to detect a 0.18 m/s difference between two independent groups, which would indicate a change in the UPDRS walking category [26], is 11 per group, i.e., 22 participants in total. Based on the assumption that about 10% of participants may drop out during the study, a target of 24 participants in total has been set.

Data collection will yield eight variables: walking speed (m/s), walking step length (m), walking cadence (steps/min), walking confidence (modified Gait Efficacy Scale score; 10–100), mobility (TUG; seconds), freezing of gait (New Freezing of Gait Questionnaire; 0–28), fear of falling (FES-I Brazil score; 16–64), and number of falls. There are two factors (group × time), with repeated measures on the time factor. Two-way analyses of variance with repeated measures at all time points for all outcomes will be reported to evaluate the statistical significance of the between-group differences. The mean between-group differences, along with 95% confidence intervals, will be reported for all outcomes. The effect of the intervention will be calculated based on intention-to-treat analyses.

This trial will be conducted according to relevant ethical frameworks and has received approval from the institutional ethical review board. It is funded by the Brazilian National Funding Agency: Fundação de Amparo à Pesquisa e Inovação do Espírito Santo (FAPES). The results will be submitted for publication in journals related to the area of neurorehabilitation, and access to the final trial dataset may be obtained from the authors based upon reasonable request.