Brain-directed Treatment to Improve Language in Adolescents and Young Adults With Down Syndrome: the Efficacy of Transcranial Direct Current Stimulation Coupled With Linguistic Training.
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 36
- 试验地点
- 2
- 主要终点
- Expressive Vocabulary
研究概览
简要总结
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.
详细描述
Down Syndrome (DS), caused by trisomy 21, is the leading genetic cause of Intellectual Disability. This chronic and complex condition disrupts normal brain development and function, resulting in deficits in cognition and adaptive behavior. A hallmark of DS is cognitive impairment, characterized by low IQ and difficulties in learning, language processing, and executive functioning-largely associated with atypical neural organization.
In recent years, substantial progress has been made in uncovering the pathogenetic mechanisms responsible for these deficits. Research has identified specific neuroanatomical and neurochemical abnormalities, including alterations in the glutamatergic and GABAergic systems, as well as dysregulation of neuromodulators such as noradrenaline, dopamine, and acetylcholine. Individuals with DS also exhibit compromised synaptic plasticity, reduced neurogenesis, and diminished neural remodeling capacity-all contributing to their unique cognitive profile.
These neurobiological insights have spurred interest in developing therapeutic interventions aimed at improving cognitive function. Although some pharmacological strategies have shown promise in preclinical and limited clinical trials, their clinical translation has often yielded limited success, underscoring the need for alternative approaches. Among these, non-invasive brain stimulation (NiBS), particularly Transcranial Direct Current Stimulation (tDCS), is emerging as a promising method to enhance cognitive and language abilities.
The primary goal of this project is to build a robust scientific basis for novel brain-targeted rehabilitation strategies, specifically to address language deficits in adolescents and young adults with DS. Given the limited research on NiBS in this population, this proof-of-concept study aims to evaluate the feasibility and efficacy of two active tDCS protocols-anodal and cathodal stimulation-targeting the left inferior frontal gyrus (IFG), both compared to a placebo (sham) stimulation condition.
This is a proof-of-concept, non-profit, single-center, prospective, randomized, double-blind, placebo-controlled trial. Both participants and outcome assessors will be blinded to treatment allocation. Thirty-six participants with DS, aged 12 to 21 years, will be randomly assigned to three groups receiving anodal, cathodal, or sham (placebo) tDCS combined with speech and language training. The intervention comprises ten sessions of either anodal tDCS, cathodal tDCS, or sham (placebo) stimulation, delivered over two consecutive weeks (five sessions per week), in conjunction with a tailored speech and language training protocol. The stimulation intensity will be set at 1 mA for 20 minutes per session, each speech and language treatment session, administered by a trained speech therapist, will last 20 minutes structured in 10 minutes of motor planning/programming and 10 minutes addressing lexical, morphosyntactic, and functional language domains.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Outcomes Assessor)
盲法说明
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.
入排标准
- 年龄范围
- 12 Years 至 21 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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.
研究组 & 干预措施
Active Anodal tDCS to the left IFG
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.
干预措施: Active Group (Active Anodal tDCS to the left IFG or Cathodal tDCS to the left IFG) (Device)
Active Cathodal tDCS to the left IFG
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.
干预措施: Active Group (Active Anodal tDCS to the left IFG or Cathodal tDCS to the left IFG) (Device)
Sham tDCS to the left IFG
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.
干预措施: Sham Group (Device)
结局指标
主要结局
Expressive Vocabulary
时间窗: 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).
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).
Expressive Vocabulary
时间窗: 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).
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).
次要结局
- 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))
- Inconsistency(T0 (baseline, Day 1), T1 (post-treatment, Day 10), T2 (3-month follow-up, Day 90))
- Verbal Span(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))
- Intelligibility(T0 (baseline, Day 1), T1 (post-treatment, Day 10), T2 (3-month follow-up, Day 90))
- Quality of sleep(T0 (baseline, Day 1), T1 (post-treatment, Day 10), T2 (3-month follow-up, Day 90))
- Assessment of Challenging Behaviors(T0 (baseline, Day 1), T1 (post-treatment, Day 10), T2 (3-month follow-up, Day 90))
- Parenting Stress Index(T0 (baseline, Day 1), T1 (post-treatment, Day 10), T2 (3-month follow-up, Day 90))
- 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))
- Health-related quality of life measure(T0 (baseline, Day 1), T1 (post-treatment, Day 10), T2 (3-month follow-up, Day 90))
研究者
Floriana Costanzo
Psychologist, PhD
Bambino Gesù Hospital and Research Institute