Non-Invasive Brain Stimulation to Improve Language in Down Syndrome.

NCT07044804 | Recruiting

• 2 other identifiers: 3406_OPBG_2024Jérôme Lejeune Foundation
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

Brief Summary

Down syndrome (DS) is associated with cognitive deficits, caused by alterations in neuroplasticity and synaptic transmission. Non-invasive brain stimulation techniques, such as transcranial direct current stimulation (tDCS), can modulate the brain's plasticity mechanisms and neurotransmitter balance. Anodal tDCS increases cortical excitability by depolarizing neurons, while cathodal tDCS decreases it through hyperpolarization. When combined with cognitive training, tDCS may produce faster and longer-lasting therapeutic effects. Although most of the neurorehabilitation studies have applied anodal excitatory stimulation, recent evidence suggests the potential cathodal inhibitory stimulation in neurodevelopmental disorders with alteration of synaptic transmission, as people with DS. Potentially both anodal and cathodal stimulation protocols could lead to positive clinical effects in DS. This proof-of-concept study is a double-blind, placebo-controlled, clinical trial aiming to evaluate the efficacy of two active tDCS protocols (anodal and cathodal) targeting the left inferior frontal gyrus (IFG) versus sham stimulation tDCS, combined with speech and language training, to improve language skills in adolescents and young adults with DS. The study also aims to identify the most effective parameters of tDCS treatment, for customization in adolescents and young adults with DS. Thirty-six participants, aged 12 to 21 years, will be randomly assigned to three groups receiving anodal, cathodal, or sham tDCS. Each participant will undergo 10 sessions of tDCS at 1 mA for 20 minutes, alongside speech and language training five times for two weeks. Neuropsychological, behavioral, biomarker (including brain-derived neurotrophic factor and neurofilament light chain), and electroencephalogram assessments will be performed at baseline, post-treatment, and three months after treatment completion. The study hypothesizes that tDCS will enhance language abilities, particularly expressive vocabulary, and modulate biomarkers of brain plasticity in DS participants. The study also hypothesizes that tDCS will enhance other cognitive and behavioral functions. Since tDCS effects may last, the study will check for improvements at the three-month. If effective, this combined approach of tDCS and language training could pave the way for new rehabilitation strategies for DS.

Conditions

Down Syndrome

Keywords

Trisomy 21; tDCS; Non-invasive brain stimulation; Speech; Neuroplasticity; BDNF; neurofilament light chain

Outcome Measures

Primary Outcomes (1)

• Expressive Vocabulary

  The primary outcome measure will be expressive vocabulary assessed by the Naming subtests of the Battery for the Assessment of Language in Children aged 4 to 12 years (BVL\_4-12).

  Assessments will be conducted at three time points: baseline (T0, day 1), immediately post-treatment (T1, day 10), and at follow-up (T2, three months).

Secondary Outcomes (11)

• Articulation, Semantic Fluency and Phonological Fluency

  Assessments will be conducted at three time points: baseline (T0, day 1), immediately post-treatment (T1, day 10), and at follow-up (T2, three months)

• Adaptive level

  T0 (baseline, Day 1), T1 (post-treatment, Day 10), T2 (3-month follow-up, Day 90)

• Psychopathological measure - behavioral and psychopathological aspects

  T0 (baseline, Day 1), T1 (post-treatment, Day 10), T2 (3-month follow-up, Day 90)

• Psychopathological measure - behavioural and emotional problems

  T0 (baseline, Day 1), T1 (post-treatment, Day 10), T2 (3-month follow-up, Day 90)

• Health-related quality of life measure

  T0 (baseline, Day 1), T1 (post-treatment, Day 10), T2 (3-month follow-up, Day 90)

Other Outcomes (2)

• Biological measures

  T0 (baseline, Day 1), T1 (post-treatment, Day 10), T2 (3-month follow-up, Day 90)

• Neurophysiological measures

  T0 (baseline, Day 1), T1 (post-treatment, Day 10), T2 (3-month follow-up, Day 90)

Study Arms (3)

Active Anodal tDCS to the left IFG

ACTIVE COMPARATOR

Anodal- tDCS will be delivered by a battery driven, constant current stimulator through a pair of saline-soaked sponge electrodes kept firm by elastic bands. The device employed will be the BrainStim+ (REF: EMS BSTIM+), a lightweight, battery-operated constant current stimulator.The active electrode will be placed on the left IFG cortex (between F5 and F7 of the extended International 10-20 system for EEG electrode placement) cortex and the reference electrode placed above the contralateral shoulder, as previously applied in DS.Stimulation intensity will be set at 1 mA; the duration of stimulation will be 20 min and will be held five consecutive daily session per week for two weeks for a total of 10 sessions. During the tDCS sessions participant will sit in a comfortable chair and a language training will be administered for 20 minutes.

Device: Active Group (Active Anodal tDCS to the left IFG or Cathodal tDCS to the left IFG)

Active Cathodal tDCS to the left IFG

ACTIVE COMPARATOR

Cathodal- tDCS the cathode will be placed on the left IFG (between F5 and F7 of the extended International 10-20 system for EEG electrode placement) cortex, while the anode will be placed above the right shoulder. The device employed will be the BrainStim+ (REF: EMS BSTIM+), a lightweight, battery-operated constant current stimulator. Stimulation intensity will be set at 1 mA; the duration of stimulation will be 20 min and will be held five consecutive daily session per week for two weeks for a total of 10 sessions. During the tDCS sessions participant will sit in a comfortable chair and a language training will be administered for 20 minutes.

Device: Active Group (Active Anodal tDCS to the left IFG or Cathodal tDCS to the left IFG)

Sham tDCS to the left IFG

SHAM COMPARATOR

In the sham condition, participants will undergone electrode placements identical to those used in either the anodal or cathodal tDCS configurations, with equal allocation to each montage. The BrainStim+ device (REF: EMS BSTIM+), a lightweight, battery-operated constant current stimulator, will be used. However, the current will be applied only briefly for 30 seconds before being ramped down in a manner imperceptible to the participant, thereby simulating the initial sensation of stimulation without delivering an active dose. Sham sessions will follow the same schedule as the active conditions-20 minutes per session, five consecutive daily sessions per week over two weeks (total of 10 sessions). During each session, participants will be seated comfortably and engage in concurrent language training.

Device: Sham Group

Interventions

Active Group (Active Anodal tDCS to the left IFG or Cathodal tDCS to the left IFG) DEVICE

Participants in the active tDCS group (Anodal tDCS or Cathodal tDCS) will receive stimulation set at 1 mA (milliampere), with a duration of 20 minutes per session. The stimulation will be administered in five consecutive sessions per day, five days a week, for two weeks, totaling 10 sessions, while participants will also undergo logopedic treatment for 20 minutes. The training protocol will consist of 10 minutes of training in motor planning and programming abilities and 10 minutes of training on the lexical, morphosyntactic, and functional aspects of language and communication.

Active Anodal tDCS to the left IFG; Active Cathodal tDCS to the left IFG

Sham Group DEVICE

For the sham condition, the same electrode placement will be used as in the anodal tDCS condition, but the current will be applied for 30 s and will be ramped down without the participant's awareness. Stimulation intensity will be set at 1 mA; the duration of stimulation will be 20 min and will be held five consecutive daily session per week for two weeks, for a total of 10 sessions. During the tDCS sessions participant will sit in a comfortable chair and a language training will be administered

Sham tDCS to the left IFG

Eligibility Criteria

• Age: 12 Years - 21 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Italian speakers participants of both genders with the presence of a free trisomy 21 documented by karyotyping
• Adolescents and young adults from 12 to 21 years old
• Mental age ≥ 4 years (as assessed by Leiter-3 at baseline)
• Scores \< 2 SD at the denomination subtest of BVL\_4-12
• Be comprehensible to closest relatives, at least in part, exhibiting consistent speech sounds mesured by Intelligibility in Context Scale (ICS): Italian (McLeod, Harrison, \& McCormack, 2012) with a cut-off of 3.5
• Informed consent/absent from each patient and Informed consent from their caregivers.

You may not qualify if:

• The presence of any neurosensory deficits, such as hypoacusis or serious visual impairments
• The presence of epilepsy, familiarity with epilepsy and major psychopathological disorders
• Scores \< 10 points at the denomination subtest of BVL\_4-12
• Ability to verbally imitate less that 7 of 10 words during an imitation screening task
• Undergoing concomitant speech therapy or psychopharmacological therapy for cognitive or behavioral improvement.

Sponsors & Collaborators

• Floriana Costanzo: lead
• Bambino Gesù Children's Hospital IRCCS: collaborator

Study Sites (1)

Bambino Gesù Children's Hospital, IRCCS

Rome, Italy, 00165, Italy

RECRUITING

Related Publications (3)

• Lopes JBP, Grecco LAC, Moura RCF, Lazzari RD, Duarte NAC, Miziara I, Melo GEL, Dumont AJL, Galli M, Santos Oliveira C. Protocol study for a randomised, controlled, double-blind, clinical trial involving virtual reality and anodal transcranial direct current stimulation for the improvement of upper limb motor function in children with Down syndrome. BMJ Open. 2017 Aug 11;7(8):e016260. doi: 10.1136/bmjopen-2017-016260.

  PMID: 28801420 BACKGROUND

• Lopes JBP, Miziara IM, Kahani D, Parreira RB, de Almeida Carvalho Duarte N, Lazzari RD, Santos LV, de Mello Monteiro CB, da Silva Cardoso DC, de Oliveira Hassel Mendes J, Dos Santos Alves VL, Silva IO, Oliveira LV, Conway BA, Galli M, Cimolin V, Oliveira CS. Brain activity and upper limb movement analysis in children with Down syndrome undergoing transcranial direct current stimulation combined with virtual reality training: study protocol for a randomized controlled trial. Trials. 2022 Jan 28;23(1):87. doi: 10.1186/s13063-022-06014-4.

  PMID: 35090554 BACKGROUND

• Faralli A, Fuca E, Lazzaro G, Menghini D, Vicari S, Costanzo F. Transcranial Direct Current Stimulation in neurogenetic syndromes: new treatment perspectives for Down syndrome? Front Cell Neurosci. 2024 Feb 22;18:1328963. doi: 10.3389/fncel.2024.1328963. eCollection 2024.

  PMID: 38456063 BACKGROUND

Related Links

• Study information brochure approved.

MeSH Terms

Conditions

Down Syndrome; Speech; Charcot-Marie-Tooth disease, Type 1F

Condition Hierarchy (Ancestors)

Intellectual Disability; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Abnormalities, Multiple; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Chromosome Disorders; Genetic Diseases, Inborn; Verbal Behavior; Communication; Behavior

Central Study Contacts

Floriana Costanzo, PsyD, PhD

CONTACT

+390668597091; floriana.costanzo@opbg.net

Elisa Fucà, PhD

CONTACT

+390668597091; elisa.fucà@opbg.net

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Masking Details: Both participants and evaluators will be blinded to the treatment conditions. To control for a possible placebo effect, the study included the control group placebo tDCS plus language training. It is well known that tDCS has a sham mode that cannot be easily detected by participants, making it possible to be used in controlled experiments and randomized controlled clinical trials. The opening of the blind will be allowed if serious adverse events occur or if the subject wants to leave the study early.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Psychologist, PhD

Model Details: This is a no profit, single center, prospective, randomized double-blind placebo controlled study to assess the superiority of tDCS active treatment to placebo. Enrollment will last 15 months, with the study expected to start in August 2024.Participants and evaluators will be blinded to treatment. Every tDCS session will be conducted during a language training in the Italian language, in order to optimize the intervention. A neuropsychological, linguistic, behavioural and functional communication assessment will be carried prior to (T0), following the end of the treatments (T1) and after three months (T2). Additional biological and neurophysiological measures will be collected. Specifically, the assessment of BDNF and NfL levels and EEG will be performed before and at the end of treatment, and at a 3 month after the end of treatment, to evaluate the involvement and changes in neuronal plasticity mechanisms in response to neuromodulation treatment and language training.

Study Record Dates

• First Submitted: June 20, 2025
• First Posted: July 1, 2025
• Study Start: January 27, 2025
• Primary Completion: March 31, 2026
• Study Completion: March 31, 2026
• Last Updated: July 4, 2025

Record last verified: 2024-08

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)