The Effects of Methylphenidate and Non-invasive Brain Stimulation on Inhibitory Control in Children With ADHD

Sponsor

Bambino Gesù Hospital and Research Institute (Other)

Overall Status

Active, not recruiting

CT.gov ID

NCT04964427

Collaborator

(none)

Enrollment

Location

Arms

20.8

Anticipated Duration (Months)

1.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The aim of this study is comparing the effects of non-pharmacological intervention (transcranial Direct Current Stimulation, tDCS) with those of drug (methylphenidate, MPH) administration in children and adolescents with ADHD.

The investigators hypothesized that tDCS would improve inhibitory control and visuo-spatial working memory as well as MPH.

Condition or Disease	Intervention/Treatment	Phase
Attention Deficit Hyperactivity Disorder	Drug: Methylphenidate Device: anodal tDCS Device: sham tDCS	N/A

Detailed Description

A sham controlled within-subjects study design will be conducted. Clinical eligibility screening will be completed at baseline. All participants will undergo an extensive neuropsychiatric evaluation in which developmental neuropsychiatrists and psychologists will evaluate the cognitive and the adaptive level, the severity of ADHD symptoms, and the presence of comorbid psychiatric disorders. After completing baseline assessment (T0), participants will be exposure to 3 conditions with an intersession-interval of 24h (T1, T2, T3): A) a single administration of 1 milliampere (mA) anodal tDCS session over the dorsolateral prefrontal cortex (DLPFC); B) a single administration of 1 mA sham tDCS session over the DLPFC; C) a single administration of immediate release MPH (Ritalin®), in accordance with the National Institute for Clinical Excellence (NICE) guidelines for ADHD (NICE, 2000). The order of the conditions will be counterbalanced across participants. After recruitment, the participants will be assigned to one of the 6 possible combinations of conditions (ABC, ACB, BAC, BCA, CBA, or CAB). The assignment will be according to a randomization order generated by a computer. The randomization information will be maintained by an independent researcher until data collection is completed. Participants will be tested on inhibitory control, by the Stop Signal Task (SST) and on working memory, by the N-Back Task, at baseline (T0), during tDCS administration (after 10 minutes of anodal and sham conditions) and after 1 hour of MPH administration. To verify that carry-over effects will not occur, the SST and the N-Back Task will be performed before each session (T1, T2, T3) and results will be compared with those obtained at baseline (T0). If the participant will not return to baseline level, another evaluation will be administered at least after two hours and, again, until participant's performance will return to baseline. Participants and parents will be blinded to tDCS conditions allocation. The tDCS will be carried out with a BrainStim stimulator.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

25 participants

Allocation:

Randomized

Intervention Model:

Crossover Assignment

Intervention Model Description:

Study participants will receive the three conditions in random order: a single dose of immediate release MPH (Ritalin®) administered according to the AIFA and NICE guidelines for ADHD; a single 1 mA anodal tDCS session over the DLPFC for 20 min a single session of sham tDCS over the DLPFC for 30s at the beginning and end of the tDCS session. The order of administration of the conditions will be counterbalanced between the participants and the conditions will be spaced apart from an interval of 24 hours.Study participants will receive the three conditions in random order:a single dose of immediate release MPH (Ritalin®) administered according to the AIFA and NICE guidelines for ADHD; a single 1 mA anodal tDCS session over the DLPFC for 20 min a single session of sham tDCS over the DLPFC for 30s at the beginning and end of the tDCS session. The order of administration of the conditions will be counterbalanced between the participants and the conditions will be spaced apart from an interval of 24 hours.

Masking:

Double (Participant, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

The Effects of Methylphenidate (MPH) and Non-invasive Brain Stimulation (tDCS) on Inhibitory Control Children With Attention-Deficit/Hyperactivity Disorder (ADHD)

Actual Study Start Date :

Feb 8, 2021

Anticipated Primary Completion Date :

Oct 2, 2022

Anticipated Study Completion Date :

Nov 2, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: anodal tDCS- sham tDCS- MPH (A) anodal tDCS at t1 (B) sham tDCS at t2 (C) MPH at t3	Drug: Methylphenidate A single dose of 5-10 mg of immediate release MPH (Ritalin®) will be administered in line with NICE and AIFA (Agenzia Italiana del Farmaco) guidelines for ADHD treatment. Other Names: Ritalin Device: anodal tDCS Anodal electrode will be positioned over the left dlPFC, according to the 10-20 EEG on the sites corresponding F3, whereas the reference electrode will be placed above the contralateral supraorbital area, corresponding to Fp2. In the active tDCS condition, the current will increase slowly during the first 30 seconds to 1 mA (ramp-up) and, at the end of the stimulation, the current will decrease slowly to 0 mA during the last 30 seconds (ramp-down). Between the ramp-up and ramp-down constant current will be delivered for 20 minutes, with a density of 0.04 mA/cm2. Device: sham tDCS In the sham tDCS condition, the stimulation will be delivered by using the same active tDCS montage, respectively left-anodal dlPFC and right-reference electrode over Fp2. Stimulation intensity will be set at 1 mA, but the current will be applied for 30 seconds and will be ramped down without the participants' awareness.
Experimental: anodal tDCS- MPH- sham tDCS (A) anodal tDCS at t1 (C) MPH at t2 (B) sham tDCS at t3	Drug: Methylphenidate A single dose of 5-10 mg of immediate release MPH (Ritalin®) will be administered in line with NICE and AIFA (Agenzia Italiana del Farmaco) guidelines for ADHD treatment. Other Names: Ritalin Device: anodal tDCS Anodal electrode will be positioned over the left dlPFC, according to the 10-20 EEG on the sites corresponding F3, whereas the reference electrode will be placed above the contralateral supraorbital area, corresponding to Fp2. In the active tDCS condition, the current will increase slowly during the first 30 seconds to 1 mA (ramp-up) and, at the end of the stimulation, the current will decrease slowly to 0 mA during the last 30 seconds (ramp-down). Between the ramp-up and ramp-down constant current will be delivered for 20 minutes, with a density of 0.04 mA/cm2. Device: sham tDCS In the sham tDCS condition, the stimulation will be delivered by using the same active tDCS montage, respectively left-anodal dlPFC and right-reference electrode over Fp2. Stimulation intensity will be set at 1 mA, but the current will be applied for 30 seconds and will be ramped down without the participants' awareness.
Experimental: sham tDCS- anodal tDCS- MPH (B) sham tDCS at t1 (A) anodal tDCS at t2 (C) MPH at t3	Drug: Methylphenidate A single dose of 5-10 mg of immediate release MPH (Ritalin®) will be administered in line with NICE and AIFA (Agenzia Italiana del Farmaco) guidelines for ADHD treatment. Other Names: Ritalin Device: anodal tDCS Anodal electrode will be positioned over the left dlPFC, according to the 10-20 EEG on the sites corresponding F3, whereas the reference electrode will be placed above the contralateral supraorbital area, corresponding to Fp2. In the active tDCS condition, the current will increase slowly during the first 30 seconds to 1 mA (ramp-up) and, at the end of the stimulation, the current will decrease slowly to 0 mA during the last 30 seconds (ramp-down). Between the ramp-up and ramp-down constant current will be delivered for 20 minutes, with a density of 0.04 mA/cm2. Device: sham tDCS In the sham tDCS condition, the stimulation will be delivered by using the same active tDCS montage, respectively left-anodal dlPFC and right-reference electrode over Fp2. Stimulation intensity will be set at 1 mA, but the current will be applied for 30 seconds and will be ramped down without the participants' awareness.
Experimental: sham tDCS- MPH- anodal tDCS (B) sham tDCS at t1 (C) MPH at t2 (A) anodal tDCS at t3	Drug: Methylphenidate A single dose of 5-10 mg of immediate release MPH (Ritalin®) will be administered in line with NICE and AIFA (Agenzia Italiana del Farmaco) guidelines for ADHD treatment. Other Names: Ritalin Device: anodal tDCS Anodal electrode will be positioned over the left dlPFC, according to the 10-20 EEG on the sites corresponding F3, whereas the reference electrode will be placed above the contralateral supraorbital area, corresponding to Fp2. In the active tDCS condition, the current will increase slowly during the first 30 seconds to 1 mA (ramp-up) and, at the end of the stimulation, the current will decrease slowly to 0 mA during the last 30 seconds (ramp-down). Between the ramp-up and ramp-down constant current will be delivered for 20 minutes, with a density of 0.04 mA/cm2. Device: sham tDCS In the sham tDCS condition, the stimulation will be delivered by using the same active tDCS montage, respectively left-anodal dlPFC and right-reference electrode over Fp2. Stimulation intensity will be set at 1 mA, but the current will be applied for 30 seconds and will be ramped down without the participants' awareness.
Experimental: MPH- anodal tDCS- sham tDCS (C) MPH at t1 (A) anodal tDCS at t2 (B) sham tDCS at t3	Drug: Methylphenidate A single dose of 5-10 mg of immediate release MPH (Ritalin®) will be administered in line with NICE and AIFA (Agenzia Italiana del Farmaco) guidelines for ADHD treatment. Other Names: Ritalin Device: anodal tDCS Anodal electrode will be positioned over the left dlPFC, according to the 10-20 EEG on the sites corresponding F3, whereas the reference electrode will be placed above the contralateral supraorbital area, corresponding to Fp2. In the active tDCS condition, the current will increase slowly during the first 30 seconds to 1 mA (ramp-up) and, at the end of the stimulation, the current will decrease slowly to 0 mA during the last 30 seconds (ramp-down). Between the ramp-up and ramp-down constant current will be delivered for 20 minutes, with a density of 0.04 mA/cm2. Device: sham tDCS In the sham tDCS condition, the stimulation will be delivered by using the same active tDCS montage, respectively left-anodal dlPFC and right-reference electrode over Fp2. Stimulation intensity will be set at 1 mA, but the current will be applied for 30 seconds and will be ramped down without the participants' awareness.
Experimental: MPH- sham tDCS- anodal tDCS (C) MPH at t1 (B) sham tDCS at t2 (A) anodal tDCS at t3	Drug: Methylphenidate A single dose of 5-10 mg of immediate release MPH (Ritalin®) will be administered in line with NICE and AIFA (Agenzia Italiana del Farmaco) guidelines for ADHD treatment. Other Names: Ritalin Device: anodal tDCS Anodal electrode will be positioned over the left dlPFC, according to the 10-20 EEG on the sites corresponding F3, whereas the reference electrode will be placed above the contralateral supraorbital area, corresponding to Fp2. In the active tDCS condition, the current will increase slowly during the first 30 seconds to 1 mA (ramp-up) and, at the end of the stimulation, the current will decrease slowly to 0 mA during the last 30 seconds (ramp-down). Between the ramp-up and ramp-down constant current will be delivered for 20 minutes, with a density of 0.04 mA/cm2. Device: sham tDCS In the sham tDCS condition, the stimulation will be delivered by using the same active tDCS montage, respectively left-anodal dlPFC and right-reference electrode over Fp2. Stimulation intensity will be set at 1 mA, but the current will be applied for 30 seconds and will be ramped down without the participants' awareness.

Outcome Measures

Primary Outcome Measures

evaluate the change in response inhibition measures [immediately after the interventions]
Compare Stop Signal Reaction Times in patients with ADHD following the administration of a single anodal tDCS session, a single sham tDCS session and a single dose of MPH

Secondary Outcome Measures

evaluate the change in other response inhibition measures [immediately after the interventions]
Reaction Times and Variability of Reaction Times of SST in patients with ADHD following the administration of a single anodal tDCS session, a single sham tDCS session and a single dose of MPH
evaluate the change in visuo-spatial working memory measure [immediately after the interventions]
Compare N-Back Correct Scores of visuo-spatial working memory task in patients with ADHD following the administration of a single anodal tDCS session, a single sham tDCS session and a single dose of MPH

Eligibility Criteria

Criteria

Ages Eligible for Study:

8 Years to 13 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Criteria: Inclusion Criteria:

Patients must receive a Diagnostic and Statistical Manual of Mental Disorders (DSM-5) oriented diagnosis of ADHD and need drug treatment for the severity of symptoms;
Intelligent Quotient (IQ) > 85;

Exclusion Criteria:

Presence of Autism Spectrum Disorders;
Presence of Mood Disorders;
Previous/current diagnosis of neurological conditions (i.e. epilepsy, neurodegenerative diseases);
Presence of Genetic Syndromes;
Presence of basal medical conditions (i.e. heart, kidney or liver diseases) which may exclude the possibility to administer MPH.