Autistic Disorders SpectrumNCT03947086
Neurostimulation for Cognitive Rehabilitation in Autistic Spectrum Disorders
A study testing Transcranial Direct Current Stimulation (TDCS)- Active and Cognitive Training in people with Autistic Disorders Spectrum, run by Federal University of Paraíba at 1 site in Brazil.
Trial 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. Read more about this study
- Who is it for?
- Ages 8 to 12 years, men only
- Conditions the study is for
- Autistic Disorders Spectrum
- What is being tested?
- Transcranial Direct Current Stimulation (TDCS)- Active and Cognitive Training
- Type of treatment
- Medical device, Lifestyle or therapy programme
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 16 participants
- Where
- 1 siteBrazil
- Study dates
- 30 Apr 2018to 30 May 2019
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 8 to 12 years
- Men only
- No healthy volunteers
- Child
Who may be able to join
- Clinical diagnosis of ASD
- Degree of mild autistic symptomatology
- Normal or corrected acuity.
Who cannot join
- Intellectual deficits
- Cardiac pacemaker or implanted metallic or electronic device
- Severe neurological disorders
- Poor skull formation
- Epilepsy
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Transcranial Direct Current Stimulation for Cognitive Rehabilitation of Children With Autistic Spectrum Disorders
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.
Read the 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
- Being tested
- Transcranial Direct Current Stimulation (TDCS)- Active, Transcranial Direct Current Stimulation (TDCS)- Sham, Cognitive Training
- Keywords
- Autistic disorder, Neuromodulation, Social cognition, Executive functions, Eye tracking
- Medical subject headings
- Child Development Disorders, Pervasive, Autistic Disorder
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Transcranial Direct Current Stimulation (TDCS)- ActiveDevice
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).
Transcranial Direct Current Stimulation (TDCS)- ShamDevice
The protocol for participants receiving simulated current is identical, but the device ceases to emit current after 30 seconds of initiation of pacing.
Cognitive TrainingBehavioural
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.
| Study group | Role | What they receive |
|---|---|---|
| Active TDCS Group | Active comparator | 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. Receives: Device: Transcranial Direct Current Stimulation (TDCS)- Active; Behavioral: Cognitive Training |
| Sham tDCS Group | Sham comparator | 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. Receives: Device: Transcranial Direct Current Stimulation (TDCS)- Sham; Behavioral: Cognitive Training |
What is being measured
The primary outcome is the main question the study is designed to answer.
Facial emotion recognition
Images of facial expressions of emotion of children of diverse ethnicities will be presented. We used 20 images of emotional expressions of the test of emotional knowledge elaborated by Izard, Hankins, Schultz, Tentracosta and King (2003). The following emotional faces of both sexes will be used: happy, sad, angry, fear / surprised and neutral, presented at random and for 4 seconds each. During the recognition of the emotional expressions, the 300 Hz binocular Eye Tracker Tobii was used to monitor eye movements.
.
Measured: The test will be measured immediately before the intervention.
Facial emotion recognition
Images of facial expressions of emotion of children of diverse ethnicities will be presented. We used 20 images of emotional expressions of the test of emotional knowledge elaborated by Izard, Hankins, Schultz, Tentracosta and King (2003). The following emotional faces of both sexes will be used: happy, sad, angry, fear / surprised and neutral, presented at random and for 4 seconds each. During the recognition of the emotional expressions, the 300 Hz binocular Eye Tracker Tobii was used to monitor eye movements.
.
Measured: The test will be measured immediately after the intervention.
Facial emotion recognition
Images of facial expressions of emotion of children of diverse ethnicities will be presented. We used 20 images of emotional expressions of the test of emotional knowledge elaborated by Izard, Hankins, Schultz, Tentracosta and King. The following emotional faces of both sexes will be used: happy, sad, angry, fear / surprised and neutral, presented at random and for 4 seconds each. During the recognition of the emotional expressions, the 300 Hz binocular Eye Tracker Tobii was used to monitor eye movements.
.
Measured: The test will be measured 4 weeks after the intervention.
Theory of mind- Verbal task
The subtest theory of mind contained in Nepsy II neuropsychological battery will be used. The test includes two tasks: the verbal task evaluates the understanding and perception of self-intention and of the other, deception, beliefs, pretending, and imitation through stories, figures, and questions. The contextual task evaluates the ability to relate a situation to emotion in a specific social context.
Measured: The test will be measured immediately before the intervention.
Theory of mind- Contextual task
The subtest theory of mind contained in Nepsy II neuropsychological battery will be used. The test includes two tasks: the verbal task evaluates the understanding and perception of self-intention and of the other, deception, beliefs, pretending, and imitation through stories, figures, and questions. The contextual task evaluates the ability to relate a situation to emotion in a specific social context.
Measured: The test will be measured immediately before the intervention.
Theory of mind- Verbal task
The subtest theory of mind contained in Nepsy II neuropsychological battery will be used. The test includes two tasks: the verbal task evaluates the understanding and perception of self-intention and of the other, deception, beliefs, pretending, and imitation through stories, figures, and questions. The contextual task evaluates the ability to relate a situation to emotion in a specific social context.
Measured: The test will be measured immediately after the intervention.
Theory of mind- Contextual task
The subtest theory of mind contained in Nepsy II neuropsychological battery will be used. The test includes two tasks: the verbal task evaluates the understanding and perception of self-intention and of the other, deception, beliefs, pretending, and imitation through stories, figures, and questions. The contextual task evaluates the ability to relate a situation to emotion in a specific social context.
Measured: The test will be measured immediately after the intervention.
Theory of mind- Verbal task
The subtest theory of mind contained in Nepsy II neuropsychological battery will be used. The test includes two tasks: the verbal task evaluates the understanding and perception of self-intention and of the other, deception, beliefs, pretending, and imitation through stories, figures, and questions. The contextual task evaluates the ability to relate a situation to emotion in a specific social context.
Measured: The test will be measured 4 weeks after the intervention.
Theory of mind- Contextual task
The subtest theory of mind contained in Nepsy II neuropsychological battery will be used. The test includes two tasks: the verbal task evaluates the understanding and perception of self-intention and of the other, deception, beliefs, pretending, and imitation through stories, figures, and questions. The contextual task evaluates the ability to relate a situation to emotion in a specific social context.
Measured: The test will be measured 4 weeks after the intervention.
Secondary outcomes (9)
Memory for Digit Span
The measure was used to evaluate the operational memory. There are two parts to the Memory for Digit Span assessment: Digits Forward and Digits Backward. Each tap distinct but interdependent cognitive functions. Digits Forward primarily taps short-term auditory memory while Digits Backward measures the child's ability to manipulate verbal information while in temporary storage. In Digits Forward, the child listens to and repeats a sequence of numbers spoken aloud by the interviewer. In Digits Backward, the child listens to a sequence of numbers and repeats them in reverse order.
Measured: The test will be measured immediately before the intervention.
Memory for Digit Span
The measure was used to evaluate the operational memory. There are two parts to the Memory for Digit Span assessment: Digits Forward and Digits Backward. Each tap distinct but interdependent cognitive functions. Digits Forward primarily taps short-term auditory memory while Digits Backward measures the child's ability to manipulate verbal information while in temporary storage. In Digits Forward, the child listens to and repeats a sequence of numbers spoken aloud by the interviewer. In Digits Backward, the child listens to a sequence of numbers and repeats them in reverse order.
Measured: The test will be measured immediately after the intervention.
Memory for Digit Span
The measure was used to evaluate the operational memory. There are two parts to the Memory for Digit Span assessment: Digits Forward and Digits Backward. Each tap distinct but interdependent cognitive functions. Digits Forward primarily taps short-term auditory memory while Digits Backward measures the child's ability to manipulate verbal information while in temporary storage. In Digits Forward, the child listens to and repeats a sequence of numbers spoken aloud by the interviewer. In Digits Backward, the child listens to a sequence of numbers and repeats them in reverse order.
Measured: The test will be measured 4 weeks after the intervention.
Trail Making Test A e B
The TMT measures attention, speed, and mental flexibility. Part A requires the individual to draw lines to connect 25 encircled numbers distributed on a page. Part A tests visual scanning, numeric sequencing, and visuomotor speed. Part B is similar except the person must alternate between numbers and letters and is believed to be more difficult and takes longer to complete. Part B tests cognitive demands including visual motor and visual spatial abilities and mental flexibility.
Measured: The test will be measured immediately before the intervention.
Trail Making Test A e B
The TMT measures attention, speed, and mental flexibility. Part A requires the individual to draw lines to connect 25 encircled numbers distributed on a page. Part A tests visual scanning, numeric sequencing, and visuomotor speed. Part B is similar except the person must alternate between numbers and letters and is believed to be more difficult and takes longer to complete. Part B tests cognitive demands including visual motor and visual spatial abilities and mental flexibility.
Measured: The test will be measured immediately after the intervention.
Trail Making Test A e B
The TMT measures attention, speed, and mental flexibility. Part A requires the individual to draw lines to connect 25 encircled numbers distributed on a page. Part A tests visual scanning, numeric sequencing, and visuomotor speed. Part B is similar except the person must alternate between numbers and letters and is believed to be more difficult and takes longer to complete. Part B tests cognitive demands including visual motor and visual spatial abilities and mental flexibility.
Measured: The test will be measured 4 weeks after the intervention.
Seven Errors Test
This test aims to evaluate executive functions globally. The test consists of two different pairs of figures: a pair of figures of one elephant, and another pair refers to a boat. Each pair has the original figure and the figure containing the errors, both appear simultaneously on the screen, side by side, and the participant must identify the errors / differences between the figures. The 300 Hz binocular Eye Tracker Tobii was used to monitor eye movements during the test.
Measured: The test will be measured immediately before the intervention.
Seven Errors Test
This test aims to evaluate executive functions globally. The test consists of two different pairs of figures: a pair of figures of one elephant, and another pair refers to a boat. Each pair has the original figure and the figure containing the errors, both appear simultaneously on the screen, side by side, and the participant must identify the errors / differences between the figures. The 300 Hz binocular Eye Tracker Tobii was used to monitor eye movements during the test.
Measured: The test will be measured immediately after the intervention.
Seven Errors Test
This test aims to evaluate executive functions globally. The test consists of two different pairs of figures: a pair of figures of one elephant, and another pair refers to a boat. Each pair has the original figure and the figure containing the errors, both appear simultaneously on the screen, side by side, and the participant must identify the errors / differences between the figures. The 300 Hz binocular Eye Tracker Tobii was used to monitor eye movements during the test.
Measured: The test will be measured 4 weeks after the intervention.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 May 2019
- Study start30 Apr 2018
- Primary completion30 Sep 2018
- Study completion30 May 2019 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (13)Papers the sponsor has linked to this study.
- Other trials for Autistic Disorders SpectrumStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- 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 between 8 and 12 years old with mild ASD. In total there will be 16 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 placebo 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. Participants and investigators will be blinded. Furthermore, everyone will receive Social Cognition Training concomitantly with neurostimulation to enhance social skills in children with ASD. Patients will undergo three social cognitive assessments: at baseline, week 2 (after stimulation), and 1 month later (follow up).
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 16 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Federal University of Paraíba
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Jéssica Bruna Santana Silva, Federal University of Paraíba
- Investigators
- Jéssica B Santana, Master, Principal investigator, Federal University of ParaíbaNatanael A Santos, PhD, Study director, Federal University of Paraíba
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03947086
- Sponsor's protocol ID
- U1111-1221-6178
- Status last verified
- May 2019
- First submitted
- 30 Apr 2019
- Last updated
- 15 May 2019
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Amatachaya A, Auvichayapat N, Patjanasoontorn N, Suphakunpinyo C, Ngernyam N, Aree-Uea B, Keeratitanont K, Auvichayapat P. Effect of anodal transcranial direct current stimulation on autism: a randomized double-blind crossover trial. Behav Neurol. 2014;2014:173073. doi: 10.1155/2014/173073. Epub 2014 Oct 30.
PubMed 25530675Amatachaya A, Jensen MP, Patjanasoontorn N, Auvichayapat N, Suphakunpinyo C, Janjarasjitt S, Ngernyam N, Aree-uea B, Auvichayapat P. The short-term effects of transcranial direct current stimulation on electroencephalography in children with autism: a randomized crossover controlled trial. Behav Neurol. 2015;2015:928631. doi: 10.1155/2015/928631. Epub 2015 Mar 12.
PubMed 25861158Jamil A, Batsikadze G, Kuo HI, Labruna L, Hasan A, Paulus W, Nitsche MA. Systematic evaluation of the impact of stimulation intensity on neuroplastic after-effects induced by transcranial direct current stimulation. J Physiol. 2017 Feb 15;595(4):1273-1288. doi: 10.1113/JP272738. Epub 2016 Nov 8.
PubMed 27723104Boggio PS, Asthana MK, Costa TL, Valasek CA, Osorio AA. Promoting social plasticity in developmental disorders with non-invasive brain stimulation techniques. Front Neurosci. 2015 Sep 1;9:294. doi: 10.3389/fnins.2015.00294. eCollection 2015.
PubMed 26388712Brunoni AR, Nitsche MA, Bolognini N, Bikson M, Wagner T, Merabet L, Edwards DJ, Valero-Cabre A, Rotenberg A, Pascual-Leone A, Ferrucci R, Priori A, Boggio PS, Fregni F. Clinical research with transcranial direct current stimulation (tDCS): challenges and future directions. Brain Stimul. 2012 Jul;5(3):175-195. doi: 10.1016/j.brs.2011.03.002. Epub 2011 Apr 1.
PubMed 22037126Couture SM, Penn DL, Roberts DL. The functional significance of social cognition in schizophrenia: a review. Schizophr Bull. 2006 Oct;32 Suppl 1(Suppl 1):S44-63. doi: 10.1093/schbul/sbl029. Epub 2006 Aug 17.
PubMed 16916889Demirtas-Tatlidede A, Vahabzadeh-Hagh AM, Pascual-Leone A. Can noninvasive brain stimulation enhance cognition in neuropsychiatric disorders? Neuropharmacology. 2013 Jan;64:566-78. doi: 10.1016/j.neuropharm.2012.06.020. Epub 2012 Jun 28.
PubMed 22749945Dillon MR, Kannan H, Dean JT, Spelke ES, Duflo E. Cognitive science in the field: A preschool intervention durably enhances intuitive but not formal mathematics. Science. 2017 Jul 7;357(6346):47-55. doi: 10.1126/science.aal4724.
PubMed 28684518Gao X, Maurer D. Influence of intensity on children's sensitivity to happy, sad, and fearful facial expressions. J Exp Child Psychol. 2009 Apr;102(4):503-21. doi: 10.1016/j.jecp.2008.11.002. Epub 2009 Jan 4.
PubMed 19124135Kucharska-Pietura K, Mortimer A. Can antipsychotics improve social cognition in patients with schizophrenia? CNS Drugs. 2013 May;27(5):335-43. doi: 10.1007/s40263-013-0047-0.
PubMed 23533009Kuo MF, Paulus W, Nitsche MA. Therapeutic effects of non-invasive brain stimulation with direct currents (tDCS) in neuropsychiatric diseases. Neuroimage. 2014 Jan 15;85 Pt 3:948-60. doi: 10.1016/j.neuroimage.2013.05.117. Epub 2013 Jun 4.
PubMed 23747962Nitsche MA, Cohen LG, Wassermann EM, Priori A, Lang N, Antal A, Paulus W, Hummel F, Boggio PS, Fregni F, Pascual-Leone A. Transcranial direct current stimulation: State of the art 2008. Brain Stimul. 2008 Jul;1(3):206-23. doi: 10.1016/j.brs.2008.06.004. Epub 2008 Jul 1.
PubMed 20633386Muszkat D, Polanczyk GV, Dias TG, Brunoni AR. Transcranial Direct Current Stimulation in Child and Adolescent Psychiatry. J Child Adolesc Psychopharmacol. 2016 Sep;26(7):590-7. doi: 10.1089/cap.2015.0172. Epub 2016 Mar 30.
PubMed 27027666
Study at a glance
From the registry record, last updated by the sponsor on 15 May 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Transcranial Direct Current Stimulation for Cognitive Rehabilitation of Children With Autistic Spectrum Disorders
- ClinicalTrials.gov ID
- NCT03947086
- Acronym / sponsor ID
- U1111-1221-6178
- Conditions
- Autistic Disorders Spectrum
- Keywords
- Autistic disorder, Neuromodulation, Social cognition, Executive functions, Eye tracking
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 16 participants (estimated)
- Lead sponsor
- Federal University of ParaíbaUniversity, hospital or other
- Study start
- 30 Apr 2018 (actual)
- Primary completion
- 30 Sep 2018 (actual)
- Study completion
- 30 May 2019 (estimated)
- First posted
- 13 May 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
- Model description
- 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 between 8 and 12 years old with mild ASD. In total there will be 16 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 placebo 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. Participants and investigators will be blinded. Furthermore, everyone will receive Social Cognition Training concomitantly with neurostimulation to enhance social skills in children with ASD. Patients will undergo three social cognitive assessments: at baseline, week 2 (after stimulation), and 1 month later (follow up).
| Arm | Type | Receives |
|---|---|---|
| Active TDCS Group | Active comparator | Device: Transcranial Direct Current Stimulation (TDCS)- Active, Behavioral: Cognitive TrainingParticipants 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. |
| Sham tDCS Group | Sham comparator | Device: Transcranial Direct Current Stimulation (TDCS)- Sham, Behavioral: Cognitive TrainingParticipants 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. |
Who may qualify
- Ages
- 8 to 12 years
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (3 listed)
- Clinical diagnosis of ASD
- Degree of mild autistic symptomatology
- Normal or corrected acuity.
Key exclusion criteria (5 listed)
- Intellectual deficits
- Cardiac pacemaker or implanted metallic or electronic device
- Severe neurological disorders
- Poor skull formation
- Epilepsy
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Transcranial Direct Current Stimulation (TDCS)- ActiveA 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). | Device | Active TDCS Group |
| Transcranial Direct Current Stimulation (TDCS)- ShamThe protocol for participants receiving simulated current is identical, but the device ceases to emit current after 30 seconds of initiation of pacing. | Device | Sham tDCS Group |
| Cognitive TrainingConsidering 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. | Behavioural | Active TDCS Group, Sham tDCS Group |
Primary outcome
Facial emotion recognition
Time frame: The test will be measured immediately before the intervention.
Images of facial expressions of emotion of children of diverse ethnicities will be presented. We used 20 images of emotional expressions of the test of emotional knowledge elaborated by Izard, Hankins, Schultz, Tentracosta and King (2003). The following emotional faces of both sexes will be used: happy, sad, angry, fear / surprised and neutral, presented at random and for 4 seconds each. During the recognition of the emotional expressions, the 300 Hz binocular Eye Tracker Tobii was used to monitor eye movements. .
Facial emotion recognition
Time frame: The test will be measured immediately after the intervention.
Images of facial expressions of emotion of children of diverse ethnicities will be presented. We used 20 images of emotional expressions of the test of emotional knowledge elaborated by Izard, Hankins, Schultz, Tentracosta and King (2003). The following emotional faces of both sexes will be used: happy, sad, angry, fear / surprised and neutral, presented at random and for 4 seconds each. During the recognition of the emotional expressions, the 300 Hz binocular Eye Tracker Tobii was used to monitor eye movements. .
Facial emotion recognition
Time frame: The test will be measured 4 weeks after the intervention.
Images of facial expressions of emotion of children of diverse ethnicities will be presented. We used 20 images of emotional expressions of the test of emotional knowledge elaborated by Izard, Hankins, Schultz, Tentracosta and King. The following emotional faces of both sexes will be used: happy, sad, angry, fear / surprised and neutral, presented at random and for 4 seconds each. During the recognition of the emotional expressions, the 300 Hz binocular Eye Tracker Tobii was used to monitor eye movements. .
Theory of mind- Verbal task
Time frame: The test will be measured immediately before the intervention.
The subtest theory of mind contained in Nepsy II neuropsychological battery will be used. The test includes two tasks: the verbal task evaluates the understanding and perception of self-intention and of the other, deception, beliefs, pretending, and imitation through stories, figures, and questions. The contextual task evaluates the ability to relate a situation to emotion in a specific social context.
Theory of mind- Contextual task
Time frame: The test will be measured immediately before the intervention.
The subtest theory of mind contained in Nepsy II neuropsychological battery will be used. The test includes two tasks: the verbal task evaluates the understanding and perception of self-intention and of the other, deception, beliefs, pretending, and imitation through stories, figures, and questions. The contextual task evaluates the ability to relate a situation to emotion in a specific social context.
Theory of mind- Verbal task
Time frame: The test will be measured immediately after the intervention.
The subtest theory of mind contained in Nepsy II neuropsychological battery will be used. The test includes two tasks: the verbal task evaluates the understanding and perception of self-intention and of the other, deception, beliefs, pretending, and imitation through stories, figures, and questions. The contextual task evaluates the ability to relate a situation to emotion in a specific social context.
Theory of mind- Contextual task
Time frame: The test will be measured immediately after the intervention.
The subtest theory of mind contained in Nepsy II neuropsychological battery will be used. The test includes two tasks: the verbal task evaluates the understanding and perception of self-intention and of the other, deception, beliefs, pretending, and imitation through stories, figures, and questions. The contextual task evaluates the ability to relate a situation to emotion in a specific social context.
Theory of mind- Verbal task
Time frame: The test will be measured 4 weeks after the intervention.
The subtest theory of mind contained in Nepsy II neuropsychological battery will be used. The test includes two tasks: the verbal task evaluates the understanding and perception of self-intention and of the other, deception, beliefs, pretending, and imitation through stories, figures, and questions. The contextual task evaluates the ability to relate a situation to emotion in a specific social context.
Theory of mind- Contextual task
Time frame: The test will be measured 4 weeks after the intervention.
The subtest theory of mind contained in Nepsy II neuropsychological battery will be used. The test includes two tasks: the verbal task evaluates the understanding and perception of self-intention and of the other, deception, beliefs, pretending, and imitation through stories, figures, and questions. The contextual task evaluates the ability to relate a situation to emotion in a specific social context.
9 secondary outcomes
Memory for Digit Span
Time frame: The test will be measured immediately before the intervention.
Memory for Digit Span
Time frame: The test will be measured immediately after the intervention.
Memory for Digit Span
Time frame: The test will be measured 4 weeks after the intervention.
Trail Making Test A e B
Time frame: The test will be measured immediately before the intervention.
Trail Making Test A e B
Time frame: The test will be measured immediately after the intervention.
Trail Making Test A e B
Time frame: The test will be measured 4 weeks after the intervention.
Seven Errors Test
Time frame: The test will be measured immediately before the intervention.
Seven Errors Test
Time frame: The test will be measured immediately after the intervention.
Seven Errors Test
Time frame: The test will be measured 4 weeks after the intervention.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 May 2019.
- Background: PubMed 25530675Amatachaya A, Auvichayapat N, Patjanasoontorn N, Suphakunpinyo C, Ngernyam N, Aree-Uea B, Keeratitanont K, Auvichayapat P. Effect of anodal transcranial direct current stimulation on autism: a randomized double-blind crossover trial. Behav Neurol. 2014;2014:173073. doi: 10.1155/2014/173073. Epub 2014 Oct 30.
- Background: PubMed 25861158Amatachaya A, Jensen MP, Patjanasoontorn N, Auvichayapat N, Suphakunpinyo C, Janjarasjitt S, Ngernyam N, Aree-uea B, Auvichayapat P. The short-term effects of transcranial direct current stimulation on electroencephalography in children with autism: a randomized crossover controlled trial. Behav Neurol. 2015;2015:928631. doi: 10.1155/2015/928631. Epub 2015 Mar 12.
- Background: PubMed 27723104Jamil A, Batsikadze G, Kuo HI, Labruna L, Hasan A, Paulus W, Nitsche MA. Systematic evaluation of the impact of stimulation intensity on neuroplastic after-effects induced by transcranial direct current stimulation. J Physiol. 2017 Feb 15;595(4):1273-1288. doi: 10.1113/JP272738. Epub 2016 Nov 8.
- Background: PubMed 26388712Boggio PS, Asthana MK, Costa TL, Valasek CA, Osorio AA. Promoting social plasticity in developmental disorders with non-invasive brain stimulation techniques. Front Neurosci. 2015 Sep 1;9:294. doi: 10.3389/fnins.2015.00294. eCollection 2015.
- Background: PubMed 22037126Brunoni AR, Nitsche MA, Bolognini N, Bikson M, Wagner T, Merabet L, Edwards DJ, Valero-Cabre A, Rotenberg A, Pascual-Leone A, Ferrucci R, Priori A, Boggio PS, Fregni F. Clinical research with transcranial direct current stimulation (tDCS): challenges and future directions. Brain Stimul. 2012 Jul;5(3):175-195. doi: 10.1016/j.brs.2011.03.002. Epub 2011 Apr 1.
- Background: PubMed 16916889Couture SM, Penn DL, Roberts DL. The functional significance of social cognition in schizophrenia: a review. Schizophr Bull. 2006 Oct;32 Suppl 1(Suppl 1):S44-63. doi: 10.1093/schbul/sbl029. Epub 2006 Aug 17.
- Background: PubMed 22749945Demirtas-Tatlidede A, Vahabzadeh-Hagh AM, Pascual-Leone A. Can noninvasive brain stimulation enhance cognition in neuropsychiatric disorders? Neuropharmacology. 2013 Jan;64:566-78. doi: 10.1016/j.neuropharm.2012.06.020. Epub 2012 Jun 28.
- Background: PubMed 28684518Dillon MR, Kannan H, Dean JT, Spelke ES, Duflo E. Cognitive science in the field: A preschool intervention durably enhances intuitive but not formal mathematics. Science. 2017 Jul 7;357(6346):47-55. doi: 10.1126/science.aal4724.
- Background: PubMed 19124135Gao X, Maurer D. Influence of intensity on children's sensitivity to happy, sad, and fearful facial expressions. J Exp Child Psychol. 2009 Apr;102(4):503-21. doi: 10.1016/j.jecp.2008.11.002. Epub 2009 Jan 4.
- Background: PubMed 23533009Kucharska-Pietura K, Mortimer A. Can antipsychotics improve social cognition in patients with schizophrenia? CNS Drugs. 2013 May;27(5):335-43. doi: 10.1007/s40263-013-0047-0.
- Background: PubMed 23747962Kuo MF, Paulus W, Nitsche MA. Therapeutic effects of non-invasive brain stimulation with direct currents (tDCS) in neuropsychiatric diseases. Neuroimage. 2014 Jan 15;85 Pt 3:948-60. doi: 10.1016/j.neuroimage.2013.05.117. Epub 2013 Jun 4.
- Background: PubMed 20633386Nitsche MA, Cohen LG, Wassermann EM, Priori A, Lang N, Antal A, Paulus W, Hummel F, Boggio PS, Fregni F, Pascual-Leone A. Transcranial direct current stimulation: State of the art 2008. Brain Stimul. 2008 Jul;1(3):206-23. doi: 10.1016/j.brs.2008.06.004. Epub 2008 Jul 1.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jéssica B Santana, Master principal investigator
Federal University of Paraíba
Natanael A Santos, PhD study director
Federal University of Paraíba
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Transcranial Direct Current Stimulation (TDCS)- Active and Cognitive Training in people with Autistic Disorders Spectrum, run by Federal University of Paraíba at 1 site in Brazil.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 15 May 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Brazil. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Facial emotion recognition (time frame: The test will be measured immediately before the intervention.). The study lists 9 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03947086, which also lists 13 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 May 2019.