Clinical trial NCT03173105: Effects of Transcranial Direct Current Stimulation With Proprioceptive Training in Blind People
Official title: Protocol Study for a Randomized Controlled Trial of the Effects of Transcranial Direct Current Stimulation (tDCS) Associated With Proprioceptive Training in Blind People
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Blindness, Acquired
Blindness Congenital
Keywords: Visually Impaired Persons
Postural Balance
Rehabilitation
Transcranial Direct Current Stimulation
Lead sponsor: Salgado Institute of Integral Health
Sponsor class: OTHER
Collaborators: name: Coordenação de Aperfeiçoamento de Pessoal de Nível Superior.
First posted: 2017-06-01
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Participants will be randomly allocated to four groups: Group 1 (G1) - active tDCS + dynamic proprioceptive exercises; Group 2 (G2) - sham tDCS + dynamic proprioceptive exercises; Group 3 (G3)- active tDCS + static proprioceptive exercises; and Group 4 (G4) - sham tDCS + static proprioceptive exercises. Randomization will be performed with the use of sealed opaque envelopes containing a card stipulating to which group the volunteer will be allocated (G1, G2, G3 or G4).
Primary purpose: TREATMENT

Brief summary: Postural control requires the integration of the vestibular, visual, and somatosensory systems. Vision, in particular, exerts a considerable influence on body sway during activities that require balance. The investigators aimed to analyze the effects of transcranial direct current stimulation (tDCS) combined with proprioceptive exercises on postural control in individuals between 18 and 55 years old, with congenital and acquired blindness.

The intervention will occur in three phases: 1 - Determine differences in postural control and gait between individuals with congenital and acquired blindness with and without the use of a guide stick when wearing shoes and when barefoot; 2 - Will be a pilot study containing 10 subjects in each group (total of 40) where a sample size estimation will be analyzed based on a gait and balance parameters result from a ten consecutive days treatment protocol consisting of tDCS plus proprioceptive; 3 - A treatment protocol will be conducted in which the participants will be allocated to four groups: G1 - active tDCS + dynamic proprioceptive exercises; G2 - sham tDCS + dynamic proprioceptive exercises; G3 - active tDCS + static proprioceptive exercises; and G4 - sham tDCS + static proprioceptive exercises.

Evaluations will involve a camera system for three-dimensional gait analysis, a force plate to measure the postural control, and electromyography to analyze the muscle activities. Dynamic stability will be determined using the Timed Up and Go test and static stability will be analyzed with the aid of the force plate.

The viability of this study will allow the determination of differences in postural control between individuals with congenital and acquired blindness, the analysis of the effect of tDCS on postural control, and the establishment of a rehabilitation protocol.

Detailed description: Ethical Aspects The study will be conducted in compliance with the principles of the Declaration of Helsinki as well as the guidelines for research involving human subjects stipulated by the National Board of Health of the Brazilian Health Ministry. Eligible individuals will receive clarifications regarding the objectives and procedures and those who agree to participate will sign a informed consentment.

Sample and recruitment The study will be conducted in three phases. First: to determine differences in postural control and gait between individuals with congenital and acquired blindness with and without a guide stick when wearing shoes and while barefoot. Second: will involve the characterization of differences in the effects of anodal tDCS on postural control and gait when stimulation is administered to different areas of the brain: primary motor cortex; somatosensory cortex; and visual cortex. Third: will involve a treatment protocol in which the participants will be randomly allocated in four groups: Group 1 - active tDCS + dynamic proprioceptive exercises; Group 2 - sham tDCS + dynamic proprioceptive exercises; Group 3 - active tDCS + static proprioceptive exercises; and Group 4 - sham tDCS + static proprioceptive exercises. Randomization will be performed with the use of sealed opaque envelopes containing a card stipulating to which group the volunteer will be allocated.

Individuals with a diagnosis of complete congenital or acquired blindness will be recruited from the community and associations that offer assistance to individuals with visual impairment. The characterization of blindness will be based on the classification of the degree of visual impairment proposed by the International Statistical Classification of Disease and the 10th Edition of the International Classification of Disease, in which visual acuity \<20/400 or \<20/200 in the better eye is classified as blindness.

With regard to the inclusion criteria: abnormalities of the optic nerve, retina disorders, glaucoma, Stargardt disease, macular degeneration, retinitis pigmentosa, congenital toxoplasmosis, congenital cataracts, congenital Leber's amaurosis, detached retina and astrocytoma. The exclusion criteria: medical diagnosis of injury affecting balance in the previous three years; use of medication affecting the central nervous system, coordination or balance; current symptoms of vertigo or dizziness; medical neurological diagnosis or symptoms suggestive of vestibular disorder; and past surgery or clinical condition of lower limbs or spinal column that can affect balance and gait. The subjects will be defined as independent if capable of locomotion without the assistance of others in all environments with or without the use of a guide stick.

Evaluation procedures Quantitative assessment of the gait The space-time gait parameters will be obtained with a wireless inertial detection (G-Sensor®, BTS Bioengineering SpA, Italy), previously validated in the gait assessment (Bugané et al., 2012; Pau et al., 2015).

Each sensor has 62mm × 36mm x 16mm dimensions, weighing 60g, and consists of a three-axis accelerometer (maximum scale ± 6g), a 3-axis gyroscope (full-scale ± 300°/s) and a magnetometer of 3 axes (full scale ± 6 Gauss). Data will be collected at a sampling frequency of 50Hz and will be transmitted via Bluetooth to a computer and processed using proper software of the device (BTS G-STUDIO, version: 2.6.12.0), which automatically provides the parameters (Galli et al 2015).

For data collection, participants will walk along a 15 m aisle at a self-selected speed and in a natural way. The inertia sensor will be set at the lower lumbar level (between L4-L5) with a semi-elastic belt. The device will acquire acceleration values (along three orthogonal axes: anteroposterior, mediolateral and superior-inferior) that will be transmitted via Bluetooth to a PC and processed with a software (BTS Bioengineering G-Studio®) to extract the following gait parameters: Step length; Gait speed; Cadence; Position and duration of the swing phase; Duration of the double support; Pelvic tilt.

Surface electromyography (sEMG) The sEMG analysis of the rectus femoris, tibialis anterior and soleus muscles will be performed with the aid of the eight-channel FREEEMG® electromyograph (BTS Engineering; Italy), with a bioelectric signal amplifier, wireless data transmission and bipolar electrodes with a total gain of 2000 within a frequency of 20 to 450 Hz. Impedance and the common rejection mode ratio of the equipment are \>1015 Ω and 60/10 Hz 92 decibel, respectively. Electrode placement will follow the sEMG for the Non-Invasive Assessment of Muscles guidelines. All electromyographic (EMG) data will be captured and digitized in 1000 frames/second using the BTS MYOLAB® software (BTS Engineering; Italy) and will be collected simultaneously with the gait kinematics performed by the (G-Walk) and both will be managed by the BTS® system and EMG Analyzer® software, respectively.

Timed Up and Go (TUG) test This test will analyze the functional mobility and dynamic balance, in which the time (in seconds) required to stand up from a standardized chair without armrests, walk three meters, turn around, return to the chair and sit down again is recorded. The participants will be instructed to perform the test at a safe, self-selected pace. The TUG will be performed with shoes and barefoot with and without a guide stick.

Stabilometry The acquisition frequency of the force plates will be 50 Hz, captured by four piezoelectric sensors measuring 400/600 mm positioned at the extremities of each force plate. The participants will be instructed to remain in quiet standing with arms alongside the body and head held in the vertical position. Measures (45 seconds) of velocity and displacement of the center of pressure in the anteroposterior and mediolateral directions will be performed barefoot and while wearing shoes.

Intervention procedure tDCS will be administered during the therapeutic intervention sessions using the tDCS device (Trans Cranial Technologies, USA), with two sponge (non-metallic) surface electrodes measuring 5 x 7 cm2 moistened with a saline solution between 15 and 140 millimoles. The participants will be randomly allocated to two types of treatment: active and sham tDCS. Anodal tDCS will be administered over the primary motor cortex, somatosensory cortex, and the visual cortex. For stimulation of the primary motor and somatosensory cortices, the anode will be positioned over the area corresponding to the lower limbs (Cz and Pz, respectively), and the stimulation of the visual cortex, the anode will be positioned over Oz. During all three stimulations, the cathode will be positioned in the medial supraorbital region. A current of 2 milliamperes (mA) will be used for twenty minutes during each proprioceptive exercise session. For sham tDCS, the electrodes will be positioned as described, but the stimulator will only be switched on for the first 30 seconds, giving the participant the initial sensation of tDCS, but no active stimulation will be administrated throughout the remainder of the session.

Proprioceptive exercises The therapeutic intervention will be divided into static and dynamic proprioceptive exercises, which will be distributed to the groups in a random fashion. The static exercises will be conducted as follows: 1) standing on toes with feet apart; 2) standing on toes with feet together; 3) standing on only right leg without support; 4) standing on only left leg without support; and 5) standing with heel of right (or left) foot touching toes of the left (or right) foot with feet in a tandem position. The exercises will be performed on an unstable surface (wobble board) on the anteroposterior (three sets) and laterolateral (three sets) axes. Each exercise will be performed in six sets of 30 seconds each, with a one-minute rest interval between sets. The dynamic proprioceptive exercises will be conducted as follows: 1) walking slowly then more quickly on a trampoline; 2) walking backward with one foot behind the other; 3) walking forward on a beam; 4) going up and down a flight of stairs; and 5) sitting on a Swiss ball (65 cm) and performing laterolateral and anteroposterior movements, circling movements and bouncing. Activities 1 to 4 will be performed in three one-minute sets and activity five will be performed in sets with 30 seconds of each movement. Throughout all exercises, a physiotherapist will remain beside the participant to avoid excessive imbalance and the risk of falls.

Sample size estimation The sample size will be estimated from Phase II where 40 participants will be randomly allocated into four groups (10 each group). Then the calculation will be considering the minimal difference between the mean of an analysis of variance results obtained from both gait speed and the displacement of the center of pressure (COP) as the primary outcome. Thus the sample size will be estimated with a unidirectional alpha of 0.05 and an 85% statistical power. The sample determined by the calculation will be increased by 20% to compensate for possible dropouts.

Statistical analysis The data will be analyzed using the Kolmogorov-Smirnov test. Parametric variables will be expressed as mean and standard deviation. Nonparametric variables will be expressed as median and inter-quartile range. The effect size will be calculated based on the difference between means of the pre-intervention and post-intervention evaluations and will be expressed with respective 95% confidence intervals.

Analysis of variance and the Kruskal-Wallis test (nonparametric variables) will be used for the analysis of the effects obtained in the three phases of the study. The Bonferroni correction for multiple comparisons will be employed as a post hoc test. The analyses of the three phases will be performed considering spatiotemporal gait variables, Gait Variable Scores, TUG, variables related to the displacement of the center of pressure (area of displacement, displacement velocity, anteroposterior sway, and mediolateral sway) as the dependent variables. The fixed independent variables in Phase I will be group (congenital and acquired blindness) and auxiliary resource (with and without guide stick). In Phase II, the fixed independent variables will be group (tDCS over the somatosensory cortex, tDCS over the primary motor cortex and tDCS over the visual cortex) and evaluation time (pre-tDCS and post-tDCS). In Phase III, the fixed independent variables will be group (active and sham tDCS), evaluation time (pre-intervention, post-intervention and follow up), and group\*evaluation time interaction. For all effects, a p-value \< 0.05 will be considered indicative of statistical significance.

Eligibility criteria: Inclusion Criteria:

* Abnormalities of the optic nerve
* Retina disorders
* Glaucoma
* Stargardt disease
* Macular degeneration
* Retinitis pigmentosa
* Congenital toxoplasmosis
* Congenital cataracts
* Congenital Leber's amaurosis
* Detached retina
* Astrocytoma

Exclusion Criteria:

* Medical diagnosis of injury affecting balance in the previous three years
* Use of medication affecting the central nervous system
* Coordination or balance
* Current symptoms of vertigo or dizziness
* Medical neurological diagnosis or symptoms suggestive of vestibular disorder
* Past surgery or clinical condition of lower limbs or spinal column that can affect balance and gait.

Primary outcomes:
measure: Postural control before and after the therapeutic proprioceptive exercises on both static and dynamic postural control in individuals with blindnes
timeFrame: The entire procedure will lasting about 10 minutes
Secondary outcomes:
measure: Gait analysis with and without the use a guide stick, and when wearing shoes or while barefoot
timeFrame: For gait analysis comparison will lasting about 30 minutes
measure: Surface electromyography
timeFrame: will lasting about 30 minutes
measure: Evaluation of functional mobility
timeFrame: The entire procedure will lasting about 5 minutes
Other outcomes:
Locations:
city: Anápolis
country: Brazil
facility: Centro Universitário de Anápolis
state: Goiás
Study officials:
affiliation: Salgado Institute of Integral Health
name: Rodolfo B Parreira, MSc
role: PRINCIPAL_INVESTIGATOR
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