tRNS Combined to Cognitive Training in Children With Dyscalculia

Improving Math Deficits in Children With Dyscalculia by tRNS: a Randomized, Double-blind Study

The present study grounds on the absence of evidence-based treatment in individuals with developmental dyscalculia (DD). At this topic, the present study will explore the potential effect of transcranial random noise stimulation (tRNS) over dorsolateral prefrontal cortex (DLPFC) or posterior parietal cortex (PPC), cerebral areas usually disrupted in individuals with DD, in addition to a usual treatment such as cognitive training.

Therefore, the investigators hypothesized that active tRNS over DLPFC or PPC combined to cognitive training will boost math and math-related skills in children and adolescents with DD, modulating theta/beta ratio around stimulated cerebral network. On the contrary, sham tRNS (placebo) over DLPFC or PPC combined to cognitive training will not have significant effect in improving math skills. Further, both active and sham tRNS combined to cognitive training will be safe and well tolerated.

Study Overview

• Status: Recruiting
• Conditions: Developmental Dyscalculia
• Intervention / Treatment: Device: Brainstim DLPFC; Behavioral: Cognitive Training; Device: Brainstim PPC; Device: Brainstim Sham

Detailed Description

The study design is randomized stratified, double blind, placebo-controlled.

A group of children and adolescents with DD will be selected and randomly assigned to three different conditions: 1. tRNS over bilateral DLPFC + cognitive training (Brainstim DLPFC); 2. tRNS over bilateral PPC (Brainstim PPC) + cognitive training; 3. sham tRNS (bilateral DLPFC/bilateral PPC; Brainstim Sham) + cognitive training.

In this project, the investigators will work to understand whether a brain-based intervention, with the use of tRNS, combined to a usual treatment can improve the outcome of individual with DD.

The protocol will allow the investigators to:

1. testing the critical role of two brain regions (DLPFC or PPC) usually involved in numerical abilities and disrupted in individuals with DD;
2. examining the neural changes (using EEG recordings) due to cognitive training without tRNS (Brainstim Sham) and with tRNS (Brainstim DLPFC; Brainstim PPC);
3. predicting training outcomes based on math-related skills;
4. testing the critical role of neural markers at developmental ages using a closed-loop tRNS to improve learning and cognitive outcomes from the training;
5. investigating the safety and tolerability of tRNS.

The investigator's overarching goal is to provide a scientific foundation for devising new rehabilitation strategies in DD.

• Study Type: Interventional
• Enrollment (Anticipated): 102
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Deny Menghini; Phone Number: 06.6859. 2875; Email: deny.menghini@opbg.net
• Study Contact Backup: Name: Giulia Lazzaro; Email: giulia.lazzaro@opbg.net

Study Locations

• Italy
  • Roma, Italy, 00165
    • Recruiting
    • Bambino Gesù Hospital and Research Institute
    • Contact: Rita Alparone; Phone Number: 06-68592859; Email: rita.alparone@opbg.net
    • Principal Investigator: Deny Menghini

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 8 years to 14 years (CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Children and adolescents with DD (Total Quotient of BDE-2 ≤ 70)
• IQ ≥ 85

Exclusion Criteria:

• Having a comorbidity with an important medical conditions;
• Having neurological diseases;
• Having Epilepsy o family history of epilepsy;
• Receiving a treatment for DD in the previous three months before the baseline screening;

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Brainstim DLPFC; tRNS over bilateral DLPFC + cognitive training	Device: Brainstim DLPFC; The active tRNS will be delivered to bilateral DLPFC for five consecutive days for two weeks for a total of ten days. tRNS will be delivered by a battery driven, random-noise current stimulator through a pair of saline-soaked sponge electrodes kept firm by elastic bands. The electrodes will be placed on the left and right DLPFC, F3 and F4 position according to the 10-20 international EEG system for electrode placement, while participants will receive a usual treatment (cognitive training). Stimulation intensity will be set at 0.75 milliampere (mA) (100-500 Hz), the duration of stimulation will be 20 min.; Other Names: tRNS over bilateral DLPFC; Behavioral: Cognitive Training; A cognitive training (Vektor; Nemmi et al., 2016) will be adiministered concomitantly to Brainstim DLPFC, Brainstim PPC, Brainstim Sham for 20 min. The training consisted of math exercises (number line, calculations) and math-related exercises (visuo-spatial working memory, mental rotation).
EXPERIMENTAL: Brainstim PPC; tRNS over bilateral PPC + cognitive training	Behavioral: Cognitive Training; A cognitive training (Vektor; Nemmi et al., 2016) will be adiministered concomitantly to Brainstim DLPFC, Brainstim PPC, Brainstim Sham for 20 min. The training consisted of math exercises (number line, calculations) and math-related exercises (visuo-spatial working memory, mental rotation).; Device: Brainstim PPC; The active tRNS will be delivered to bilateral PPC for five consecutive days for two weeks for a total of ten days. tRNS will be delivered by a battery driven, random-noise current stimulator through a pair of saline-soaked sponge electrodes kept firm by elastic bands. The electrodes will be placed on the left and right PPC, P3 and P4 position according to the 10-20 international EEG system for electrode placement, while participants will receive a usual treatment (cognitive training). Stimulation intensity will be set at 0.75mA (100-500 Hz), the duration of stimulation will be 20 min.; Other Names: tRNS over bilateral PPC
SHAM_COMPARATOR: Brainstim Sham; Sham tRNS (bilateral DLPFC/bilateral PPC) + cognitive training	Behavioral: Cognitive Training; A cognitive training (Vektor; Nemmi et al., 2016) will be adiministered concomitantly to Brainstim DLPFC, Brainstim PPC, Brainstim Sham for 20 min. The training consisted of math exercises (number line, calculations) and math-related exercises (visuo-spatial working memory, mental rotation).; Device: Brainstim Sham; The same electrode placement will be used as in the stimulation conditions (Brainstim DLPFC or Brainstim PPC), but the current will be applied for 30 s and will be ramped down without the participants awareness, and will be held five consecutive days for two weeks for a total of ten days.; Other Names: Sham tRNS (bilateral DLPFC/bilateral PPC)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number Line	The proportion of patients with change of at least 1 SD in the "number line task" of the Diagnostic battery for Dyscalculia (BDE 2, Biancardi et al., 2016) in Brainstim DLPFC and Brainstim PPC than in Brainstim Sham.	immediately after the intervention, one week and three months after the intervention

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Total Quotient	The proportion of patients with change in the "Total Quotient" of the BDE 2 (Biancardi et al., 2016) in Brainstim DLPFC and Brainstim PPC than in Brainstim Sham.	immediately after the intervention, one week and three months after the intervention
Numerical Quotient	The proportion of patients with change in the "Numerical Quotient" of the BDE 2 (Biancardi et al., 2016) in Brainstim DLPFC and Brainstim PPC than in Brainstim Sham.	immediately after the intervention, one week and three months after the intervention
Calculation Quotient	The proportion of patients with change in the "Calculation Quotient" of the BDE 2 (Biancardi et al., 2016) in Brainstim DLPFC and Brainstim PPC than in Brainstim Sham.	immediately after the intervention, one week and three months after the intervention
Number Sense Quotient	The proportion of patients with change in the "Number Sense Quotient" of the BDE 2 (Biancardi et al., 2016) in Brainstim DLPFC and Brainstim PPC than in Brainstim Sham.	immediately after the intervention, one week and three months after the intervention
Mental multiplications and additions	The proportion of patients with change in the Mental Multiplications and Mental Additions tasks of the Diagnostic battery for Dyscalculia 1 (Biancardi et al., 2004) in Brainstim DLPFC and Brainstim PPC than in Brainstim Sham.	immediately after the intervention, one week and three months after the intervention
Tempo Test Rekenen	The proportion of patients with change in the total scores of the Tempo Test Rekenen (De Vos, 1992) in Brainstim DLPFC and Brainstim PPC than in Brainstim Sham.	immediately after the intervention, one week and three months after the intervention
Geometric Puzzle	The proportion of patients with change in the total scores of the Geometric Puzzle (Nepsy II, Korkman et al., 2011) in Brainstim DLPFC and Brainstim PPC than in Brainstim Sham.	immediately after the intervention, one week and three months after the intervention
Math computerized task	The proportion of patients with change in a math computerized task (Math Proc, PEBL) in Brainstim DLPFC and Brainstim PPC than in Brainstim Sham.	immediately after the intervention, one week and three months after the intervention
Motivation and study strategies Questionnaire	The proportion of patients with change (lower score means better outcome) in the Motivation and study strategies Questionnaire from 8 to 15 ages (AMOS 8-15, Cornoldi et al., 2005) in Brainstim DLPFC and Brainstim PPC than in Brainstim Sham.	immediately after the intervention, one week and three months after the intervention
Math Anxiety Questionnaire	The proportion of patients with change (lower score means better outcome) in the Math Anxiety Questionnaire (MARS, Saccani and Cornoldi, 2005) in Brainstim DLPFC and Brainstim PPC than in Brainstim Sham.	immediately after the intervention, one week and three months after the intervention
Sleep quality	The proportion of patients with change (lower score means better outcome) in the Sleep Disturbance Scale for Children (SDSC, Bruni et al., 1996) in Brainstim DLPFC and Brainstim PPC than in Brainstim Sham.	immediately after the intervention, one week and three months after the intervention
Parental stress	The proportion of patients with change (higher score means better outcome) in the Parent Stress Index (PSI, Guarino et al., 2014) in Brainstim DLPFC and Brainstim PPC than in Brainstim Sham.	immediately after the intervention, one week and three months after the intervention
Emotional/behavioural problems	The proportion of patients with change (lower score means better outcome) in the Cross-symptom assessment scales of the Kiddie-Sads- present and lifetime version-Diagnostic and Statistical Manual of Mental Disorders 5 (K-SADS- DSM-5, Kaufman et al., 2016) in Brainstim DLPFC and Brainstim PPC than in Brainstim Sham.	immediately after the intervention, one week and three months after the intervention
Math improvement at school	The proportion of patients with change in math markers in the transcript (scale from 0 to 10, where 10 is the best level and 0 the worst) in Brainstim DLPFC and Brainstim PPC than in Brainstim Sham.	three months after the intervention
Theta/Beta ratio	The proportion of patients with reduction of theta/beta ratio in Brainstim DLPFC and Brainstim PPC than in Brainstim Sham.	immediately after the intervention, one week and three months after the intervention
Verbal and visuo-spatial working-memory	The proportion of patients with change in the index of verbal and visuo-spatial n-back (more score means better outcome) in Brainstim DLPFC and Brainstim PPC than in Brainstim Sham.	immediately after the intervention, one week and three months after the intervention
Incidence of Treatment-Emergent Adverse Events [Safety and tolerability]	The proportion of patients with change in the questionnaire of safety and tolerability (Questionnaire of adverse effect; Brunoni et al., 2011) in Brainstim DLPFC and Brainstim PPC will be the same than in Brainstim Sham.	immediately after the intervention, one week and three months after the intervention

Collaborators and Investigators

• Sponsor: Bambino Gesù Hospital and Research Institute

Publications and helpful links

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Study record dates

Study Major Dates

• Study Start (ACTUAL): September 2, 2019
• Primary Completion (ANTICIPATED): January 5, 2024
• Study Completion (ANTICIPATED): May 5, 2024

Study Registration Dates

• First Submitted: January 15, 2020
• First Submitted That Met QC Criteria: January 23, 2020
• First Posted (ACTUAL): January 27, 2020

Study Record Updates

• Last Update Posted (ACTUAL): February 10, 2023
• Last Update Submitted That Met QC Criteria: February 9, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Keywords: Adolescents; Children; EEG; non-invasive brain stimulation; transcranial random noise stimulation; tRNS; transcranial electrical stimulation; neurodevelopmental disorders; numerical abilities
• Additional Relevant MeSH Terms: Mental Disorders; Nervous System Diseases; Neurologic Manifestations; Neurobehavioral Manifestations; Neurodevelopmental Disorders; Communication Disorders; Learning Disabilities; Dyscalculia
• Other Study ID Numbers: 1547_OPBG_2018

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No