ASD, Autism
Conditions
Keywords
tDCS, QEEG, ERP, ASD, Autism, verbal fluency, empathy, noninvasive brain stimulation
Brief summary
Interventional, prospective, randomized, double-blind, placebo-controlled and parallel assignment study, in which patients with Autism Spectrum Disorder (ASD) are two types of intervention by transcranial random noise stimulation (tRNS), to improve verbal fluency and empathy.
Detailed description
Interventional, prospective, randomized, double-blind, placebo-controlled and parallel assignment study, in which patients receive three types of intervention tRNS: one group received 35 sessions focused on the fronto-temporal cortex, another group received 35 sessions focused on the temporal fusiform cortex and last placebo group was operated with 35 sessions tRNS. After brain noninvasive stimulation sessions, a blind analysis of the improvement in verbal fluency and empathy in patients with autism spectrum disorder is made. For each patient included a follow up period of three months will be established.
Interventions
DEVICEtRNS Fronto-temporal cortex
This group receive 35 sessions of tRNS over fronto-temporal cortex
DEVICEtRNS over fusiform temporal cortex
This group receive 35 sessions of tRNS over fusiform temporal cortex
DEVICEtRNS with sham
the subjects receive 35 session with sham
Sponsors
Spanish Foundation for Neurometrics Development
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
5 Years to 12 Years
Healthy volunteers
No
Inclusion criteria
* Patients between 5 and 12 years. * Meet DSM-IV criteria for autism spectrum disorder. * Patients who have been diagnosed at least 2 years before inclusion in the study.
Exclusion criteria
* Acute visual or hearing loss. * Traumatic brain injury. * Other neurological disorders: migraine, epilepsy, tuberous sclerosis ... * Trauma at birth. * Mental retardation. * Pregnancy.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Verbal Fluency | During 3 months of intensive speech therapy during tRNS sessions | Goal: Improve in verbal fluency in ASD children between 5 and 12 years. We use D-KEFS (Delis-Kaplan Executive Function System Delis Kaplan Sorting Test), Verbal Fluency Subtest - Category Condition. Description: The verbal fluency Category test evaluates fluent productivity in the verbal domain by asking participants to generate exemplars belonging to the category animals, and subsequently, boys´ names. Participants were given 60 s to do it. Values: Category scores were based on the average number of items generated in the two categories (animals and boys´names) during 60 s. Time Frame: Baseline (Before treatment) and 1 day Post-treatment (after completing 3 months of intensive speech therapy during tRNS sessions) |
| Sociability | During 3 months of intensive speech therapy during tRNS sessions | Goal: Evaluate emphaty with CARS scale in autism spectrum disorder children between 5 and 12 years after tRNS sessions. CARS (Childhood Autism Rating Scale) by Shopler & Reichler (1971) in Spanish version EVAI (Escala de Valoración de Autismo Infantil) by Leal-Soto, F.; Aguirre, L.P. y Williams, E.E. Description: 15 items in the scale that evaluate: Relating to people, Imitative Behavior, Emotional Response, Body Use, Object Use, Adaptation to Change, Visual Response, Listening Response, Perceptive Response, Fear or Anxiety, Verbal Communication, Non-Verbal Communication, Activity level, Level and consistency of Intellective Relations and General Impressions. Values: The CARS scores range from 15 to 60, with lower scores indicating better outcome. It classifies the child as not autistic (below 30), moderately autistic (30-36.5) or severely autistic (above 36.5) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Ratio Theta/Beta After tDCS | During 3 months of intensive speech therapy during tDCS sessions | The purpose of the present study was to determine if the theta/beta ratio, and theta and beta separately, correlate with behavioral parameters, and if these measures discriminate between children a with Autism Spectrum disorder (ASD) and normal gender- and age-matched controls before and after tDCS intervention in ASD children between 5 and 12 years old. |
| Theta Amplitude in T5 After tDCS | During 3 months of intensive speech therapy during tRNS sessions | Evaluate QEEG (brainwave changes in frequency bandfs and amplitude) after tRNS intervention in ASD children between 5 and 12 years old |
| Reaction Time in ECPT Before tDCS | During 3 months of intensive speech therapy during tRNS sessions | ERP & Behaviour changes in ASD children after tDCS |
| Omission Errors Before tDCS | During 3 months of intensive speech therapy during tRNS sessions | ERP and behaviour changes in ASD children before tDCS |
| Commission Errors Before tDCS | During 3 months of intensive speech therapy during tDCS sessions | ERP and Behaviour changes in ASD children before tDCS |
| Ratio Theta/Beta Before tDCS | During 3 months of intensive speech therapy during tRNS sessions | The purpose of the present study was to determine if the theta/beta ratio, and theta and beta separately, correlate with behavioral parameters, and if these measures discriminate between children a with Autism Spectrum disorder (ASD) and normal gender- and age-matched controls before and after tRNS intervention in ASD children between 5 and 12 years old. |
| Reaction Time After tDCS | During 3 months of intensive speech therapy during tDCS sessions | ERP and behaviour Changes in ASD children after tDCS |
| Omissions Errors After tDCS | During 3 months of intensive speech therapy during tDCS sessions | ERP and behaviour Changes in ASD children after tDCS |
| Commission Errors After tDCS | During 3 months of intensive speech therapy during tDCS sessions | ERP and behaviour Changes in ASD children after tDCS |
| P3b Wave Amplitude After tDCS | During 3 months of intensive speech therapy during tDCS sessions | ERP and behaviour Changes in ASD children after tDCS |
| P3b Wave Amplitude Before tDCS | During 3 months of intensive speech therapy during tRNS sessions | ERP and behaviour Changes in ASD children before tDCS |
| Theta Amplitude in T5 Before tDCS | During 3 months of intensive speech therapy during tRNS sessions | The purpose of the present study was to determine if the theta/beta ratio, and theta and beta separately, correlate with behavioral parameters, and if these measures discriminate between children a with Autism Spectrum disorder (ASD) and normal gender- and age-matched controls before and after tRNS intervention in ASD children between 5 and 12 years old. |
Countries
United Kingdom
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| tRNS Fronto-temporal Cortex This group receive 35 sessions of tRNS over fronto-temporal cortex
tRNS Fronto-temporal cortex: This group receive 35 sessions of tRNS over fronto-temporal cortex | 75 |
| tRNS Over Fusiform Temporal Cortex This group receive 35 sessions of tRNS over fusiform temporal cortex
tRNS over fusiform temporal cortex: This group receive 35 sessions of tRNS over fusiform temporal cortex | 75 |
| tRNS With Sham This group receive 35 sessions with sham
tRNS with sham: the subjects receive 35 session with sham | 59 |
| Total | 209 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Lack of Efficacy | 0 | 0 | 16 |
Baseline characteristics
| Characteristic | tRNS Fronto-temporal Cortex | tRNS Over Fusiform Temporal Cortex | tRNS With Sham | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 75 Participants | 75 Participants | 59 Participants | 209 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Continuous | 7.5 years STANDARD_DEVIATION 1.98 | 6.9 years STANDARD_DEVIATION 2.1 | 7.2 years STANDARD_DEVIATION 2.3 | 7.2 years STANDARD_DEVIATION 2.12 |
| Age, Customized 10-12 years | 11.2 years STANDARD_DEVIATION 0.48 | 10.1 years STANDARD_DEVIATION 0.69 | 10.8 years STANDARD_DEVIATION 0.88 | 10.7 years STANDARD_DEVIATION 0.68 |
| Age, Customized 4-6 years | 5.1 years STANDARD_DEVIATION 0.8 | 4.8 years STANDARD_DEVIATION 1.17 | 5.3 years STANDARD_DEVIATION 0.75 | 5.06 years STANDARD_DEVIATION 0.91 |
| Age, Customized 7-9 years | 7.2 years STANDARD_DEVIATION 0.9 | 8.4 years STANDARD_DEVIATION 0.73 | 7.8 years STANDARD_DEVIATION 1.1 | 7.8 years STANDARD_DEVIATION 0.91 |
| Region of Enrollment Spain | 75 participants | 75 participants | 59 participants | 209 participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 75 Participants | 75 Participants | 59 Participants | 209 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 1 / 75 | 2 / 75 | 0 / 59 |
| serious Total, serious adverse events | 0 / 75 | 0 / 75 | 0 / 59 |
Outcome results
Primary
Sociability
Goal: Evaluate emphaty with CARS scale in autism spectrum disorder children between 5 and 12 years after tRNS sessions. CARS (Childhood Autism Rating Scale) by Shopler & Reichler (1971) in Spanish version EVAI (Escala de Valoración de Autismo Infantil) by Leal-Soto, F.; Aguirre, L.P. y Williams, E.E. Description: 15 items in the scale that evaluate: Relating to people, Imitative Behavior, Emotional Response, Body Use, Object Use, Adaptation to Change, Visual Response, Listening Response, Perceptive Response, Fear or Anxiety, Verbal Communication, Non-Verbal Communication, Activity level, Level and consistency of Intellective Relations and General Impressions. Values: The CARS scores range from 15 to 60, with lower scores indicating better outcome. It classifies the child as not autistic (below 30), moderately autistic (30-36.5) or severely autistic (above 36.5)
Time frame: During 3 months of intensive speech therapy during tRNS sessions
Population: Time frame: Baseline Before treatment and after completing 3 months of intensive speech therapy during tRNS sessions.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| tRNS Fronto-temporal Cortex | Sociability | before tRNS | 30.6 units on a scale | Standard Deviation 1.9 |
| tRNS Fronto-temporal Cortex | Sociability | after tRNS | 19.4 units on a scale | Standard Deviation 2.1 |
| tRNS Over Fusiform Temporal Cortex | Sociability | before tRNS | 32.1 units on a scale | Standard Deviation 2.2 |
| tRNS Over Fusiform Temporal Cortex | Sociability | after tRNS | 20.2 units on a scale | Standard Deviation 1.8 |
| tRNS With Sham | Sociability | before tRNS | 31.8 units on a scale | Standard Deviation 3.4 |
| tRNS With Sham | Sociability | after tRNS | 30.1 units on a scale | Standard Deviation 2.5 |
Primary
Verbal Fluency
Goal: Improve in verbal fluency in ASD children between 5 and 12 years. We use D-KEFS (Delis-Kaplan Executive Function System Delis Kaplan Sorting Test), Verbal Fluency Subtest - Category Condition. Description: The verbal fluency Category test evaluates fluent productivity in the verbal domain by asking participants to generate exemplars belonging to the category animals, and subsequently, boys´ names. Participants were given 60 s to do it. Values: Category scores were based on the average number of items generated in the two categories (animals and boys´names) during 60 s. Time Frame: Baseline (Before treatment) and 1 day Post-treatment (after completing 3 months of intensive speech therapy during tRNS sessions)
Time frame: During 3 months of intensive speech therapy during tRNS sessions
Population: Time frame: Baseline Before treatment and after completing 3 months of intensive speech therapy during tRNS sessions.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| tRNS Fronto-temporal Cortex | Verbal Fluency | before tRNS | 9.3 units on a scale | Standard Deviation 1.3 |
| tRNS Fronto-temporal Cortex | Verbal Fluency | after tRNS | 8.3 units on a scale | Standard Deviation 1.2 |
| tRNS Over Fusiform Temporal Cortex | Verbal Fluency | before tRNS | 10.5 units on a scale | Standard Deviation 1.6 |
| tRNS Over Fusiform Temporal Cortex | Verbal Fluency | after tRNS | 10.4 units on a scale | Standard Deviation 1.1 |
| tRNS With Sham | Verbal Fluency | after tRNS | 10 units on a scale | Standard Deviation 0.9 |
| tRNS With Sham | Verbal Fluency | before tRNS | 9.9 units on a scale | Standard Deviation 1.1 |
Secondary
Commission Errors After tDCS
ERP and behaviour Changes in ASD children after tDCS
Time frame: During 3 months of intensive speech therapy during tDCS sessions
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| tRNS Fronto-temporal Cortex | Commission Errors After tDCS | 6 number of commission errors in VCPT task | Standard Deviation 0.2 |
| tRNS Over Fusiform Temporal Cortex | Commission Errors After tDCS | 8 number of commission errors in VCPT task | Standard Deviation 1.1 |
| tRNS With Sham | Commission Errors After tDCS | 19 number of commission errors in VCPT task | Standard Deviation 0.9 |
Secondary
Commission Errors Before tDCS
ERP and Behaviour changes in ASD children before tDCS
Time frame: During 3 months of intensive speech therapy during tDCS sessions
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| tRNS Fronto-temporal Cortex | Commission Errors Before tDCS | 6 number of omission errors VCPT task | Standard Deviation 0.2 |
| tRNS Over Fusiform Temporal Cortex | Commission Errors Before tDCS | 8 number of omission errors VCPT task | Standard Deviation 1.1 |
| tRNS With Sham | Commission Errors Before tDCS | 19 number of omission errors VCPT task | Standard Deviation 0.9 |
Secondary
Omission Errors Before tDCS
ERP and behaviour changes in ASD children before tDCS
Time frame: During 3 months of intensive speech therapy during tRNS sessions
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| tRNS Fronto-temporal Cortex | Omission Errors Before tDCS | 85 number of errors during ECPT task | Standard Deviation 5.2 |
| tRNS Over Fusiform Temporal Cortex | Omission Errors Before tDCS | 91 number of errors during ECPT task | Standard Deviation 3.2 |
| tRNS With Sham | Omission Errors Before tDCS | 88 number of errors during ECPT task | Standard Deviation 4.6 |
Secondary
Omissions Errors After tDCS
ERP and behaviour Changes in ASD children after tDCS
Time frame: During 3 months of intensive speech therapy during tDCS sessions
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| tRNS Fronto-temporal Cortex | Omissions Errors After tDCS | 68 number of omission errors in VCPT task | Standard Deviation 2.3 |
| tRNS Over Fusiform Temporal Cortex | Omissions Errors After tDCS | 57 number of omission errors in VCPT task | Standard Deviation 4.7 |
| tRNS With Sham | Omissions Errors After tDCS | 20 number of omission errors in VCPT task | Standard Deviation 1.8 |
Secondary
P3b Wave Amplitude After tDCS
ERP and behaviour Changes in ASD children after tDCS
Time frame: During 3 months of intensive speech therapy during tDCS sessions
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| tRNS Fronto-temporal Cortex | P3b Wave Amplitude After tDCS | 2.1 MicroVolts or Amplitude P3b wave | Standard Deviation 0.25 |
| tRNS Over Fusiform Temporal Cortex | P3b Wave Amplitude After tDCS | 1.8 MicroVolts or Amplitude P3b wave | Standard Deviation 0.65 |
| tRNS With Sham | P3b Wave Amplitude After tDCS | 0.4 MicroVolts or Amplitude P3b wave | Standard Deviation 0.32 |
Secondary
P3b Wave Amplitude Before tDCS
ERP and behaviour Changes in ASD children before tDCS
Time frame: During 3 months of intensive speech therapy during tRNS sessions
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| tRNS Fronto-temporal Cortex | P3b Wave Amplitude Before tDCS | 0.5 MicroVolts or Amplitude P3b wave | Standard Deviation 0.12 |
| tRNS Over Fusiform Temporal Cortex | P3b Wave Amplitude Before tDCS | 0.7 MicroVolts or Amplitude P3b wave | Standard Deviation 0.4 |
| tRNS With Sham | P3b Wave Amplitude Before tDCS | 0.3 MicroVolts or Amplitude P3b wave | Standard Deviation 0.2 |
Secondary
Ratio Theta/Beta After tDCS
The purpose of the present study was to determine if the theta/beta ratio, and theta and beta separately, correlate with behavioral parameters, and if these measures discriminate between children a with Autism Spectrum disorder (ASD) and normal gender- and age-matched controls before and after tDCS intervention in ASD children between 5 and 12 years old.
Time frame: During 3 months of intensive speech therapy during tDCS sessions
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| tRNS Fronto-temporal Cortex | Ratio Theta/Beta After tDCS | 12 Ratio theta/beta after tRNS | Standard Deviation 1.1 |
| tRNS Over Fusiform Temporal Cortex | Ratio Theta/Beta After tDCS | 14 Ratio theta/beta after tRNS | Standard Deviation 0.52 |
| tRNS With Sham | Ratio Theta/Beta After tDCS | 25 Ratio theta/beta after tRNS | Standard Deviation 0.77 |
Secondary
Ratio Theta/Beta Before tDCS
The purpose of the present study was to determine if the theta/beta ratio, and theta and beta separately, correlate with behavioral parameters, and if these measures discriminate between children a with Autism Spectrum disorder (ASD) and normal gender- and age-matched controls before and after tRNS intervention in ASD children between 5 and 12 years old.
Time frame: During 3 months of intensive speech therapy during tRNS sessions
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| tRNS Fronto-temporal Cortex | Ratio Theta/Beta Before tDCS | 25 Ratio theta/beta before tRNS | Standard Deviation 0.88 |
| tRNS Over Fusiform Temporal Cortex | Ratio Theta/Beta Before tDCS | 30 Ratio theta/beta before tRNS | Standard Deviation 1.1 |
| tRNS With Sham | Ratio Theta/Beta Before tDCS | 26 Ratio theta/beta before tRNS | Standard Deviation 0.53 |
Secondary
Reaction Time After tDCS
ERP and behaviour Changes in ASD children after tDCS
Time frame: During 3 months of intensive speech therapy during tDCS sessions
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| tRNS Fronto-temporal Cortex | Reaction Time After tDCS | 690 Reaction Time measuring in Milliseconds | Standard Deviation 10.4 |
| tRNS Over Fusiform Temporal Cortex | Reaction Time After tDCS | 556 Reaction Time measuring in Milliseconds | Standard Deviation 7.4 |
| tRNS With Sham | Reaction Time After tDCS | 714 Reaction Time measuring in Milliseconds | Standard Deviation 3.2 |
Secondary
Reaction Time in ECPT Before tDCS
ERP & Behaviour changes in ASD children after tDCS
Time frame: During 3 months of intensive speech therapy during tRNS sessions
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| tRNS Fronto-temporal Cortex | Reaction Time in ECPT Before tDCS | 756 Milliseconds | Standard Deviation 23.5 |
| tRNS Over Fusiform Temporal Cortex | Reaction Time in ECPT Before tDCS | 698 Milliseconds | Standard Deviation 34.2 |
| tRNS With Sham | Reaction Time in ECPT Before tDCS | 722 Milliseconds | Standard Deviation 18.9 |
Secondary
Theta Amplitude in T5 After tDCS
Evaluate QEEG (brainwave changes in frequency bandfs and amplitude) after tRNS intervention in ASD children between 5 and 12 years old
Time frame: During 3 months of intensive speech therapy during tRNS sessions
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| tRNS Fronto-temporal Cortex | Theta Amplitude in T5 After tDCS | 2.2 MicroVolts | Standard Deviation 0.41 |
| tRNS Over Fusiform Temporal Cortex | Theta Amplitude in T5 After tDCS | 1.5 MicroVolts | Standard Deviation 0.36 |
| tRNS With Sham | Theta Amplitude in T5 After tDCS | 3.3 MicroVolts | Standard Deviation 0.84 |
Secondary
Theta Amplitude in T5 Before tDCS
The purpose of the present study was to determine if the theta/beta ratio, and theta and beta separately, correlate with behavioral parameters, and if these measures discriminate between children a with Autism Spectrum disorder (ASD) and normal gender- and age-matched controls before and after tRNS intervention in ASD children between 5 and 12 years old.
Time frame: During 3 months of intensive speech therapy during tRNS sessions
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| tRNS Fronto-temporal Cortex | Theta Amplitude in T5 Before tDCS | 3.2 MicroVolts | Standard Deviation 0.3 |
| tRNS Over Fusiform Temporal Cortex | Theta Amplitude in T5 Before tDCS | 2.7 MicroVolts | Standard Deviation 0.11 |
| tRNS With Sham | Theta Amplitude in T5 Before tDCS | 3.5 MicroVolts | Standard Deviation 0.5 |