Novel Tailored Network-based rTMS Treatments in Alzheimer's Disease: an Integrated Multiimaging Approach
试验速览
- 阶段
- 不适用
- 发起方
- 入组人数
- 60
- 试验地点
- 2
- 主要终点
- Change in ADAS-Cog scale scores
研究概览
简要总结
Severe alterations of brain networks connectivity have been described in Alzheimer's disease (AD). Repetitive Transcranial Magnetic Stimulation (rTMS) has gained evidence as an effective tool to modulate brain networks connectivity, leading to a recovery or reorganization of both local and remote brain regions functionally connected to the stimulated area. The investogators propose an innovative tailored network-based rTMS treatment to ameliorate cognitive symptoms in mild AD, through the boosting of connectivity within brain networks affected by AD pathophysiology. The combination of the proposed intervention with an integrated multi-modal imaging approach will allow to evaluate the neural mechanisms underlying the clinical response to the treatment and to define quantitative markers of clinical impact on AD. If successful, the present proposal would immediately impact on patient's quality of life, with important implications for the time and costs of delivery of rehabilitative services.
详细描述
Currently, no effective cure is available for Alzheimer's disease (AD). Repetitive Transcranial Magnetic Stimulation (rTMS) has gained increasing attention as a potential treatment for various neurological and psychiatric disorders, but available rTMS studies are flawed by inaccurate anatomical targeting, inadequate sample size, unsatisfactory controls and lacking blindness. To date, the elective target area of rTMS interventions in AD has been the dorsolateral prefrontal cortex (DLPFC), a core area of the Central Executive network (CEN), which plays a key role in regulating executive functions, attention and working memory. While the CEN has recently been described as dysfunctional in AD, AD pathophysiology has been mainly associated with the breakdown of the Default Mode network (DMN) and with structural disconnection of its parietal nodes. The DMN plays a crucial role in episodic memory retrieval and incorporates various brain regions, among which parietal areas are highly connected with the rest of the brain. The present multicenter, double-blind, randomized and placebo-controlled study has the ambition to provide evidence of the efficacy of two tailored network-based rTMS treatments in mild AD, through the enhancement of connectivity of CEN and DMN. Innovative integrated multi-modal imaging investigations will further enrich this proposal allowing to identify quantifiable markers underlying the clinical impact of rTMS on AD.
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
- Triple (Participant, Care Provider, Outcomes Assessor)
盲法说明
The study will be a double blind trial, i.e. both patients and clinicians involved in the assessment will be blind to treatment allocation.
入排标准
- 年龄范围
- 55 Years 至 85 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Mini-Mental State Examination score >=16, <=24
- •Anti-cholinesterase treatment for at least 3 months prior the start date
排除标准
- •Enrollment in other clinical and pharmacological trials
- •Previous evidence of any other CNS disorder (e.g. epilepsy, infectious diseases, frontotemporal, Parkinson or Pick's disease)
- •History of major psychiatric disorders
- •History of alchol or substance abuse
- •Stress-related skin problems
- •Current consumption of psychiatric medication
- •Presence of metal implants or any implanted electronics
结局指标
主要结局
Change in ADAS-Cog scale scores
时间窗: At baseline (T0), up to 4 weeks (T1), through study completion, an average of 6 months (T2)
A brief neuropsychological assessment used to assess the severity of cognitive symptoms of dementia
次要结局
- Change in MRI measures of functional and structural connectivity(At baseline (T0), up to 4 weeks (T1), through study completion, an average of 6 months (T2))
- Change in brain connectivity(At baseline (T0), up to 4 weeks (T1), through study completion, an average of 6 months (T2))
- Change in CANTAB battery scores(At baseline (T0), up to 4 weeks (T1), through study completion, an average of 6 months (T2))
- Change in brain plasticity(At baseline (T0), up to 4 weeks (T1), through study completion, an average of 6 months (T2))
研究者
Debora Brignani
Principal Investigator
IRCCS Centro San Giovanni di Dio Fatebenefratelli