Neurostimulation for Cognitive Rehabilitation in Autistic Spectrum Disorders

NCT ID: NCT03947086

Last Updated: 2019-05-15

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: NA
• Total Enrollment: 16 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-04-30
• Study Completion Date: 2019-05-30

Brief Summary

This study is a clinical trial aims investigate the effects of neurostimulation in the treatment of children with mild ASD, specifically the action of tDCS on social cognition skills. tDCS can modulate neuronal activity in patients with ASD. Specifically, this technique has shown to be a promising tool in the promotion of social neuroplasticity, aiming at more adaptive social interactions. In this sense, it was hypothesized that participants treated with active tDCS will present better performance in social cognition tests than those submitted to sessions with simulated current.

Detailed Description

Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder that has multiple causes and very heterogeneous degrees. The main symptoms involve deficits in social interactions, difficulties in verbal and nonverbal communication, repetitive and stereotyped movements, and restricted patterns of interest. In the context of ASD rehabilitation, there is no specific treatment for autism so far, being the behavioral therapy the most used therapeutic strategy, but with still unsatisfactory results. Transcranial Direct Current Stimulation (tDCS) has been shown to be a promising technique for the treatment of different disorders, including ASD. The tDCS consists of electrical signals emitted through two electrodes in different areas of the scalp, according to the purpose of the study. The anodic current reduces the firing threshold of the neurons that are located in the cortex (that is, they increase the spontaneous firing of these neurons), whereas the cathodic current increases the firing threshold of the neurons (that is, it inhibits the activity of these neurons). Considering neuroplasticity mechanisms as fundamental in cognitive processing, tDCS becomes a promising tool in neuropsychological rehabilitation in the treatment of autistic symptoms. Previous research using protomagnetic resonance spectroscopy (H-MRS) showed lower levels of N-acetyl aspartate (NAA, a marker of mitochondrial function and neuronal density) in the left DLFPC (F3) of autistic patients, compared to healthy individuals. The findings suggest that left DLFPC dysfunction may be a component of the pathogenesis of autism. Such aspects could explain why anodic neurostimulation in F3 can improve the efficacy of autism treatment through the beneficial effects on the cognitive processes associated with DLFPC activity, such as attention and memory, executive functions, and social cognition. Social cognition can be understood as a neurobiological process that facilitates the interpretation of social signs, leading individuals to behave adaptively. In this perspective, investigations have been made that use noninvasive neuromodulatory techniques as promising tools for the promotion of social neuroplasticity, that is, the modulation of the functional and structural substrates of the nervous system associated with social cognition aiming at more adaptive social interactions.In this sense, this study is a sham-controlled, double-blind, randomized clinical trial aiming to evaluate the efficacy of anodic tDCS in aspects of social cognition of children with mild ASD. Considering that tDCS can modulate neuronal activity in patients with ASD, presented as a promising tool in the promotion of social neuroplasticity, it was hypothesized that participants treated with active current will present better performance in the social cognition tests than those submitted to sessions with simulated current. Participants treated with active current will present less number and duration of fixations in the ocular tracing during the execution of the test of recognition of emotional expressions than those submitted to the sessions with simulated current. Furthermore, cognitive processes such as executive functions are essential for social cognition because they enable the individual to engage in socially relevant activities, make decisions and behaviors to achieve goals. Deficits in social cognition as well as executive functioning have been considered central elements in the understanding and functionality of people with ASD. Thus, it was hypothesized that participants who are treated with active current will present better performance in the tests of executive functions than those submitted to the sessions with simulated current. Participants treated with active current will present less number and duration of fixations during ocular screening in the executive function test than those submitted to the simulated current sessions. Considering that there were no prior data on the effects of tDCS on patients with ASD using the primary outcome measure of the present study, a formal sample size calculation was not possible; thus, it was estimated that enrolling 20 patients would be a reasonable approach for an exploratory trial. Patients are being recruited from the appointment of rehabilitators of multidisciplinary rehabilitation centers for temporary or permanent disability and global developmental disorders in Paraíba, Brazil. Children diagnosed with ASD according DSM-V, will be randomized to two groups, one with active stimulation (1.5 mA) and the other with a sham current, in which the anode will be positioned over the left dorsolateral prefrontal cortex (F3), while the cathode (reference electrode) will be placed in the right supraorbital area. The intervention will be applied for 5 consecutive days for 20 minutes. Furthermore, everyone will receive Social Cognition Training concomitantly with neurostimulation to enhance social skills in children with ASD. To control adverse effects, reports of patients with feelings/sensations of itching, tingling, burning, headache or other discomfort (1 none, 2 mild, 3 moderate, or 4 strong) will be recorded, along with whether this effect could be related to stimulation on a Likert scale; 1 (no relation) to 5 (strongly related).

The Descriptive and inferential statistical analyzes will be performed through SPSS (Statistical package for the social sciences), version 20. The design of the statistical analyzes is based on previous literature studies of randomized and placebo-controlled clinical trials using tDCS. The intention-to-treat analysis will be used with the last observation carried forward method for patients who initiate treatment and receive at least 1 session. In this way, all participants, including in case of withdrawal of the treatment before its completion, will be included in the analysis. It will be used as significance level p <0.05.

The descriptive statistics will be used to describe the clinical and sociodemographic characteristics, as well as the primary and secondary outcomes of each group in T0. The groups will be compared using Student's t test for continuous variables, or chi-square, for categorical variables.

The evaluation and efficacy of tDCS in all variables of the primary and secondary outcomes will be examined with mixed two-way ANOVA, repeated measures, one dependent variable and two independent variables, one intra-group (time, with 3 levels, T0, T2 and T3), and between-groups (two levels: Active, Sham). Covariance analyzes (ANCOVA) will be used to identify significant differences between groups using the T0 scores as covariables. In addition, adverse effects will be analyzed using the chi-square test.

Linear logistic regression will be used to identify predictors of response. The independent variables are: tDCS active and sham, the predictive variables, analyzed one at a time, will be: age and severity of symptoms. Patients will undergo three social cognitive assessments: at baseline, week 2 (after stimulation), and 1 month later. Adverse effects will be computed at each session. Thus, this clinical trial aims to investigate the combined effects of transcranial direct current stimulation and social cognition training in improving the social skills of children with ASD.

Conditions

Autistic Disorders Spectrum

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Active TDCS Group

Participants will receive active Transcranial Direct Current Stimulation (TDCS) (1.5 mA). Furthermore, everyone will receive Social Cognition Training concomitantly with neurostimulation to enhance social skills.

Group Type: ACTIVE_COMPARATOR

Transcranial Direct Current Stimulation (TDCS)- Active

Intervention Type: DEVICE

A constant current stimulator (TCT Research Limited) will be used using electrodes of 5 × 5 cm2 embedded in saline (0.9 % NaCl) and application of 1.5 mA current for 20 minutes for 5 consecutive days. The cathode will be positioned in the right supra-orbital region, and while the anode will have the following provision in the left dorsolateral prefrontal cortex (F3).

Cognitive Training

Intervention Type: BEHAVIORAL

Considering that the effects of TDCS are potentiated when applied during the execution of a task (online) (Miniussi, & Ruzzoli, 2013), in the present study all participants received cognitive training, performed concomitantly with neurostimulation.

Cognitive training consists of two parts: standardized tasks directed to social cognition and activities that stimulate executive functions. The first part consists of tasks contained in a battery of social games (Gao & Maurer, 2009; Dillon, Kannan, Dean, Spelke, & Duflo, 2017). While the tasks directed to the executive domain are, namely: running mazes, assembling figures, completing parts of figures and the Super Lynx Memory Game. All participants, regardless of whether they underwent active or simulated stimulation, received cognitive training, respecting the ethical principles of ensuring therapeutic assistance to those involved.

Sham tDCS Group

Participants will receive sham TDCS. The protocol is identical for placebo stimulation, but the current will stop after 30 seconds from the start of stimulation. Furthermore, everyone will receive Social Cognition Training concomitantly with neurostimulation to enhance social skills.

Group Type: SHAM_COMPARATOR

Transcranial Direct Current Stimulation (TDCS)- Sham

Intervention Type: DEVICE

The protocol for participants receiving simulated current is identical, but the device ceases to emit current after 30 seconds of initiation of pacing.

Cognitive Training

Intervention Type: BEHAVIORAL

Considering that the effects of TDCS are potentiated when applied during the execution of a task (online) (Miniussi, & Ruzzoli, 2013), in the present study all participants received cognitive training, performed concomitantly with neurostimulation.

Cognitive training consists of two parts: standardized tasks directed to social cognition and activities that stimulate executive functions. The first part consists of tasks contained in a battery of social games (Gao & Maurer, 2009; Dillon, Kannan, Dean, Spelke, & Duflo, 2017). While the tasks directed to the executive domain are, namely: running mazes, assembling figures, completing parts of figures and the Super Lynx Memory Game. All participants, regardless of whether they underwent active or simulated stimulation, received cognitive training, respecting the ethical principles of ensuring therapeutic assistance to those involved.

Interventions

Transcranial Direct Current Stimulation (TDCS)- Active

A constant current stimulator (TCT Research Limited) will be used using electrodes of 5 × 5 cm2 embedded in saline (0.9 % NaCl) and application of 1.5 mA current for 20 minutes for 5 consecutive days. The cathode will be positioned in the right supra-orbital region, and while the anode will have the following provision in the left dorsolateral prefrontal cortex (F3).

Intervention Type: DEVICE

Transcranial Direct Current Stimulation (TDCS)- Sham

The protocol for participants receiving simulated current is identical, but the device ceases to emit current after 30 seconds of initiation of pacing.

Intervention Type: DEVICE

Cognitive Training

Considering that the effects of TDCS are potentiated when applied during the execution of a task (online) (Miniussi, & Ruzzoli, 2013), in the present study all participants received cognitive training, performed concomitantly with neurostimulation.

Cognitive training consists of two parts: standardized tasks directed to social cognition and activities that stimulate executive functions. The first part consists of tasks contained in a battery of social games (Gao & Maurer, 2009; Dillon, Kannan, Dean, Spelke, & Duflo, 2017). While the tasks directed to the executive domain are, namely: running mazes, assembling figures, completing parts of figures and the Super Lynx Memory Game. All participants, regardless of whether they underwent active or simulated stimulation, received cognitive training, respecting the ethical principles of ensuring therapeutic assistance to those involved.

Intervention Type: BEHAVIORAL

Eligibility Criteria

Inclusion Criteria

• Clinical diagnosis of ASD
• Degree of mild autistic symptomatology
• Normal or corrected acuity.

Exclusion Criteria

• Intellectual deficits
• Cardiac pacemaker or implanted metallic or electronic device
• Severe neurological disorders
• Poor skull formation
• Epilepsy

• Minimum Eligible Age: 8 Years
• Maximum Eligible Age: 12 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

Federal University of Paraíba

OTHER

Sponsor Role: lead

Responsible Party

Jéssica Bruna Santana Silva

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Jéssica B Santana, Master

Role: PRINCIPAL_INVESTIGATOR

Federal University of Paraíba

Natanael A Santos, PhD

Role: STUDY_DIRECTOR

Federal University of Paraíba

Locations

Gabriela Medeiros

João Pessoa, Paraíba, Brazil

Countries

Brazil

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Other Identifiers

U1111-1221-6178

Identifier Type: -

Identifier Source: org_study_id