A Double-blind, Randomized, Sham-controlled, Crossover Pilot Study Evaluating the Effect of Transcranial Direct Current Stimulation (tDCS) Targeting the Right Inferior Frontal Gyrus on Inhibitory Control in Patients With PSP.
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 入组人数
- 20
- 试验地点
- 1
- 主要终点
- To evaluate the effect of anodal tDCS targeting the right inferior frontal gyrus (IFG) on a motor-modality cognitive inhibition task, the Stop Signal Task (SST), in patients with PSP.
研究概览
简要总结
Progressive supranuclear palsy (PSP) is a rare neurodegenerative disease with a prevalence estimated at 6 per 100,000 in France and a rapidly progressive course. In its classic form (known as the Richardson type), it presents with a predominantly axial Parkinsonian syndrome, postural instability with early falls, oculomotor disorders, and cognitive and behavioral disturbances. Apart from levodopa, which may provide a modest improvement in Parkinsonian syndrome in some patients, the current therapeutic approach relies primarily on rehabilitation techniques, with no proven efficacy.
Cognitive-behavioral symptoms are common in this disease and are primarily characterized by impaired executive functions, linked to dysfunction of the frontal cortex. They often have a devastating effect on quality of life, are associated with an increased risk of falls, and represent a considerable burden for caregivers. Among these symptoms, apathy is the most commonly described symptom. Impulsivity, associated with impaired inhibitory control, is present in 32-74% of cases and may coexist with apathy.
Cognitive and behavioral inhibition depends on a complex brain network that includes, among others, the right inferior frontal gyrus (IFG), the dorsolateral prefrontal cortex, the supplementary motor area, the motor cortex, and the basal ganglia. It has recently been shown that patients with PSP have impaired functional connectivity between the right LFC and other brain structures in the network, and that neurotransmitter deficits in the right LFC correlate with their impulsivity Alongside pharmacological approaches, non-invasive brain stimulation techniques are rapidly expanding as a potential therapeutic tool. Transcranial direct current stimulation (tDCS), by modulating cortical excitability, is a promising technique. It is simple to administer and has demonstrated efficacy in several clinical settings.
Furthermore, a recent meta-analysis of 45 clinical studies shows that single or repeated tDCS sessions could modestly but significantly improve the inhibitory response-measured by reaction time in the stop-signal paradigm-especially when active (anodal) stimulation was applied to the right GFI. These studies primarily involved healthy subjects. A few studies have examined the effects of tDCS in neurodegenerative diseases and in PSP. These studies are still preliminary, involving small sample sizes, but are encouraging. Among these, a randomized study comparing tDCS to sham tDCS demonstrated a beneficial effect of a single-session tDCS session targeting the dorsolateral prefrontal cortex on verbal fluency in patients with PSP.
The hypothesis of our study is that applying tDCS stimulation over the right GFI will improve certain cognitive functions and reduce behavioral impulsivity in patients.
Very little data on tDCS in PSP is available to date. Only three studies have been published. With very different designs-including only one randomized trial comparing tDCS to sham tDCS-these studies evaluated the effects of tDCS applied to the dorsolateral prefrontal cortex or to motor and premotor areas on language and motor symptoms, respectively.
In this randomized, double-blind, controlled study, the investigators propose to explore the effects of tDCS on the right GFI on executive functions and, more specifically, on inhibitory control. Another strength of our study is that only patients with proven frontal cerebral hypometabolism on FDG-PET-MRI will be included, which will allow us to test the effect of tDCS on a clearly dysfunctional neural network. Furthermore, as a secondary objective, the investigators will be able to assess whether the effects of tDCS depend on the intensity and/or topography of cerebral hypometabolism.
The neurophysiological effects of a single tDCS session appear to last up to 60 to 90 minutes. In this proof-of-concept study, the assessment tests were deliberately chosen for their short administration time and low test-retest effect. Finally, the Stop Signal Test, already used in this population, is widely used and well-standardized.
This pilot study will provide initial data on the cognitive and motor effects of a tDCS session on the GFI, with a focus on inhibition. Given the limited effectiveness of symptomatic treatments-particularly pharmacological ones-having a new option capable of improving cognitive and/or behavioral performance would have a significant impact on the quality of life of patients and their families. tDCS has the advantage of being easily accessible and generally well-tolerated by patients and could eventually be administered in patients' homes.
If our study demonstrates an improvement in certain cognitive/motor functions, it would lead to a larger-scale study with repeated sessions to assess its benefits over a longer period.
Finally, if an improvement in executive functions is demonstrated in PSP, this could apply to other neurodegenerative diseases.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 40 Years 至 89 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Aged 40 to 89 years
- •Patients with probable PSP according to the MDS-9 diagnostic criteria
- •BREF score >10;
- •18-FDG PET-MRI performed no more than 6 months prior to enrollment and showing:
- •Glucose hypometabolism defined as > 2.5 SD compared to an atlas of healthy subjects and
- •No severe right frontal cortical atrophy according to F Pasquier's global cortical atrophy scale 53
- •Concomitant treatments must have been stable for at least 4 weeks prior to enrollment and must remain stable throughout participation
- •Patient must have provided written informed consent
- •Patient must be enrolled in a social security program
- •Patient must be able to understand French and comply with the protocol
- •Women must use adequate contraceptive measures for the duration of the clinical trial (in accordance with CTFG recommendations)
排除标准
- •Left-handed Patients;
- •Patients with severe apraxia that interferes with performance of the SST (at the investigator's discretion)
- •Known visual or hearing impairment that prevents performance of cognitive tests or the stop-signal test;
- •History of severe psychiatric or neurological disorders other than PSP;
- •Known significant brain injury(ies) (stroke, tumor, inflammation, post-traumatic, etc.), at the investigator's discretion
- •Atrophy of the right frontal lobe ≥3 on the F Pasquier Global Cortical Atrophy Scale 53
- •History of epilepsy and seizures (or cerebral impairment with unexplained loss of consciousness), severe cardiac disorders, neurosurgical procedures, or severe or frequent headaches;
- •Presence of a cardiac, neural, drug-delivery, or cerebral stimulator
- •Presence of cerebral medical devices (such as vascular clips or electronically sensitive devices), intracerebral or intracochlear metal implants,
- •Patients with any electrically, magnetically, or mechanically activated implant
- •Patients suffering from a serious, life-threatening condition such as congestive heart failure, chronic obstructive pulmonary disease (COPD), or active neoplasia
- •Patients with skin conditions (dermatitis, psoriasis, or eczema) or lesions on the scalp or skull that preclude tDCS
- •Patients under legal guardianship or protective supervision
- •Pregnant or breastfeeding women
- •For patients in the ancillary study, contraindication to MRI: Presence of metallic foreign bodies
研究组 & 干预措施
tDCS Active (first visit) + tDCS sham (second visit)
Each participant will receive active tDCS then sham tDCS during two 20-minute sessions spaced one month apart
干预措施: tDCS, or transcranial direct current stimulation (Device)
sham tDCS (fist visit) + active tDCS (second visit)
Each participant will receive sham tDCS then active tDCS during two 20-minute sessions spaced one month apart
干预措施: tDCS, or transcranial direct current stimulation (Device)
结局指标
主要结局
To evaluate the effect of anodal tDCS targeting the right inferior frontal gyrus (IFG) on a motor-modality cognitive inhibition task, the Stop Signal Task (SST), in patients with PSP.
时间窗: during the hour before each tDCS session and within 1 hour after each tDCS session
Stop Signal Reaction Time (SSRT) during the SST (seconds)
次要结局
- Safety Assessment(within 1 hour after each tDCS session)
- To evaluate, in PSP, the effect of anodal tDCS targeting the right GFI on the components of cognitive inhibition assessed by the SST(during the hour before each tDCS session and within 1 hour after each tDCS session)
- To evaluate, within the PSP, the effect of anodal tDCS targeting the right GFI on scores on the following neuropsychological assessments of verbal cognitive inhibition(during the hour before each tDCS session and within 1 hour after each tDCS session)
- To evaluate, within the PSP, the effect of anodal tDCS targeting the right GFI on scores on the following neuropsychological assessments of perseverative motor behavior(during the hour before each tDCS session and within 1 hour after each tDCS session)
- To evaluate, within the PSP, the effect of anodal tDCS targeting the right GFI on scores on the following neuropsychological assessments of other executive functions(during the hour before each tDCS session and within 1 hour after each tDCS session)
- To evaluate, within the PSP, the effect of anodal tDCS targeting the right GFI on scores on the following neuropsychological assessments of social cognition(during the hour before each tDCS session and within 1 hour after each tDCS session)
- To evaluate, within the PSP, the effect of anodal tDCS targeting the right GFI on scores on the following neuropsychological assessments of overall cognitive efficiency(during the hour before each tDCS session and within 1 hour after each tDCS session)
- To evaluate, in the PSP, the effect of anodal tDCS targeting the right GFI on motor and bulbar symptoms(during the hour before each tDCS session and within 1 hour after each tDCS session)
- To evaluate the effect of anodal tDCS targeting the right GFI on motor function in PSP(during the hour before each tDCS session and within 1 hour after each tDCS session)
- To analyze the effects of tDCS on brain metabolism patterns as assessed by 18-FDG PET-MRI(before and after each tDCS session)
- To evaluate the clinical effects of tDCS on patients' clinical characteristics(Baseline, before and after each tDCS session)
- Assess participants' perception and acceptance of tDCS stimulation(within 1 hour after each tDCS session)