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

ConditionDown Syndrome

Trial statusRecruiting

Trial phaseNot applicable

Trial typeInterventional

Biological sexAll

Age12-21

SponsorFloriana Costanzo

About this trial

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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

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

Disqualifiers

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

Trial design

Design model

Parallel

Treatments tested in this trial

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.
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

Treatment groups

36 Participants

are divided into 3 treatment groups

Group A: Active Anodal tDCS to the left IFGActive comparator 1 intervention

Group B: Active Cathodal tDCS to the left IFGActive comparator 1 intervention

Group C: Sham tDCS to the left IFGSham comparator 1 intervention

Trial outcomes

Primary outcomes

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).

Time frame

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

Articulation, Semantic Fluency and Phonological Fluency

These subtests from the Battery for the Assessment of Language in Children aged 4 to 12 years (BVL\_4-12) assess various language abilities: articulation evaluates the clarity of speech sounds; naming measures the ability to retrieve and produce the correct names of pictured objects; semantic fluency tests the capacity to generate words within a given category; and phonological fluency assesses the ability to produce words beginning with specific letters. Together, these measures provide a comprehensive evaluation of expressive language skills in participants.

Time frame

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

Adaptive Behavior Assessment System - Second Edition (ABAS-II) Scale to obtain the parent's observations about the youth's behaviour and gives a complete overview of child and adolescent adaptive behaviours.

Time frame