Efficacy and Auditory Biomarker Analysis of Fronto-Temporal Transcranial Direct Current Stimulation (tDCS) in Targeting Cognitive Impairment Associated With Recent-onset Schizophrenia: A Randomized Double-blind Sham-controlled Trial
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 发起方
- 入组人数
- 60
- 试验地点
- 8
- 主要终点
- Cognitive response
研究概览
简要总结
Background: In parallel to the traditional symptomatology, deficits in cognition (memory, attention, reasoning, social functioning) contribute significantly to disability and suffering in individuals with schizophrenia. Cognitive deficits have been closely linked to alterations in early auditory processes (EAP) that occur in auditory cortical areas. Preliminary evidence indicates that cognitive deficits in schizophrenia can be improved with a reliable and safe non-invasive brain stimulation technique called tDCS (transcranial Direct Current Stimulation). However, a significant proportion of patients derive no cognitive benefits after tDCS treatment. Further, the neurobiological mechanisms of cognitive changes after tDCS have been poorly explored in trials and are thus still unclear.
Method: The study is designed as a randomized, double-blind, 2-arm parallel-group, sham controlled, 4-centers trial. Sixty participants with recent-onset schizophrenia and cognitive impairment will be randomly allocated to receive either active (n=30) or sham (n=30) tDCS (20-min, 2-mA, 10 sessions during 5 consecutive weekdays). The anode will be placed over the left dorsolateral prefrontal cortex and the cathode over the left auditory cortex. Cognition, tolerance, symptoms, general outcome and EAP (measured with EEG and multimodal MRI) will be assessed prior to tDCS (baseline), after the 10 sessions, and at 1- and 3-month follow-up. The primary outcome will be the number of responders, defined as participants demonstrating a cognitive improvement ≥Z=0.5 from baseline on the MATRICS Consensus Cognitive Battery total score at 1-month follow-up. Additionally, we will measure how differences in EAP modulate individual cognitive benefits from active tDCS and whether there are changes in EAP measures in responders after active tDCS.
Discussion: Besides proposing a new fronto-temporal tDCS protocol by targeting the auditory cortical areas, we aim to conduct an RCT with follow-up assessments up to 3-months and a large sample size. In addition, this study will allow identifying and assessing the value of a wide range of neurobiological EAP measures for predicting and explaining cognitive deficits improvement after tDCS. The results of this trial will constitute a step toward the use of tDCS as a therapeutic tool for the treatment of cognitive impairment in recent-onset schizophrenia.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
Blinding will be maintained at several levels: participants, research staff members including investigators and data analysts. If different from the investigator, care providers will be also blinded to intervention. Blinding for the tDCS condition will be achieved for the research staff members who will administer the tDCS by the use of a randomization code (see details in §16c) and for the participants by ensuring identical appearance and sensation for both active and sham conditions. Outcome assessments, imaging and biological data will be collected and analysed by research staff members blind to group assignment and different from the staff member who will administer the tDCS.
入排标准
- 年龄范围
- 18 Years 至 35 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •The inclusion criteria include:
- •subjects of both genders, diagnosed with recent-onset schizophrenia (first 3 years of illness), confirmed through the Structured Clinical Interview for the American Psychiatric Association Diagnostic and Statistical Manual of Mental Disorders, 5th edition (SCID-5);
- •aged 18-35 years;
- •intelligence quotient (IQ) > 55;
- •cognitive deficit confirmed by a MCCB (MATRICS Cognitive Consensus Battery) total score T-score < 40;
- •the subjects should be receiving stable doses of antipsychotics for ≥ 4 weeks;
- •the subjects are covered by a public health insurance.
排除标准
- •pregnant (controlled by urine pregnancy test in females of childbearing age) or breastfeeding women;
- •unstable or acute medical conditions;
- •subjects who receive involuntary treatment or guardianship;
- •history of cranioencephalic trauma with loss of consciousness or central nervous system diseases that affect the brain;
- •use of drugs that affect cognitive performance such as anticholinergic agents and benzodiazepines;
- •current diagnosis of substance abuse or history of substance dependence in the last 6 months, except nicotine;
- •MRI (Magnetic Resonance Imaging), PET (Positron Emission Tomography) or tDCS (transcranial Direct Current Stimulation) contraindications
结局指标
主要结局
Cognitive response
时间窗: at 1-month follow-up
Number of responders at 1-month after tDCS, defined as the proportion of patients demonstrating a cognitive improvement greater than or equal to Z=0.5 from baseline on the MATRICS Consensus Cognitive Battery total score (MCCB). The MCCB is a gold-standard standardized test battery to assess cognitive functions in patients with schizophrenia. This criterion has been used and validated in both antipsychotic and cognitive remediation trials in schizophrenia.
次要结局
- Clinical response 1(at inclusion; at 1-week; at 1-month follow-up; at 3-months follow-up)
- Response marker 1(at inclusion)
- Response marker 2(at inclusion)
- Clinical response 7(at inclusion; at 1-week; at 1-month follow-up; at 3-months follow-up)
- Response marker 4(at inclusion)
- Long term cognitive response(at inclusion; at 3-months follow-up)
- Clinical response 2(at inclusion; at 1-week; at 1-month follow-up; at 3-months follow-up)
- Clinical response 3(at inclusion; at 1-week; at 1-month follow-up; at 3-months follow-up)
- Clinical response 4(at inclusion; at 1-week; at 1-month follow-up; at 3-months follow-up)
- Outcome response 1(at inclusion; at 1-month follow-up; at 3-months follow-up)
- Tolerance 1(at 1-week)
- Tolerance 2(at 1-week)
- Cognitive domain response(at inclusion; at 1-month follow-up; at 3-months follow-up)
- Clinical response 5(at inclusion; at 1-week; at 1-month follow-up; at 3-months follow-up)
- Clinical response 6(at inclusion; at 1-week; at 1-month follow-up; at 3-months follow-up)
- Outcome response 2(at inclusion; at 1-month follow-up; at 3-months follow-up)
- Response marker 3(at inclusion)
- Response marker 5(at inclusion)
- Response predictor 3(at inclusion; at 1-month follow-up)
- Response predictor 4(at inclusion; at 1-month follow-up)
- Response predictor 1(at inclusion; at 1-month follow-up)
- Response predictor 2(at inclusion; at 1-month follow-up)
- Response predictor 5(at inclusion; at 1-month follow-up)
- Response predictor 6(at inclusion; at 1-month follow-up)