tDCS Combined With rTMS for the Treatment of Negative Symptoms in Patients With Schizophrenia: a Randomized Controlled Trial
试验速览
- 阶段
- 不适用
- 状态
- Enrolling By Invitation
- 入组人数
- 120
- 试验地点
- 1
- 主要终点
- Changes in the Scale for Assessment of Negative Symptoms (SANS)
研究概览
简要总结
Despite major advances in the field of psychopharmacology in recent years, the majority of treated schizophrenia patients retain disabling symptoms, most commonly a variety of negative symptoms. Currently, clinical treatment of schizophrenia remains dominated by pharmacological control. The current use of antipsychotic medications is effective in controlling the positive symptoms of schizophrenia, but has little effect on the negative symptoms. Neuroimaging and neurophysiological studies have shown that negative symptoms are associated with abnormal brain activity in the combined right and left dorsolateral prefrontal and temporoparietal joint regions, and that physical therapy techniques can modulate cortical activity. Therefore, this study aims to investigate the efficacy of transcranial direct current stimulation(tDCS) combined with repetitive transcranial magnetic stimulation(rTMS) on negative symptoms in patients with schizophrenia and to explore possible mechanisms.
The double-blind randomized placebo-controlled study comparing active tDCS stimulation combined with active rTMS stimulation, active rTMS stimulation combined with sham tDCS stimulation, and active tDCS stimulation combined with sham rTMS stimulation to sham tDCS stimulation combined with sham rTMS stimulation at 4 weeks of treatment and 2 weeks of follow-up in patients with predominantly negative symptoms with schizophrenia was studied for efficacy. In addition to the primary observation of changes in the Negative Symptom Assessment Scale (SANS), secondary outcomes include changes in Positive and Negative symptom scale (PANSS) total and negative total scores, changes in the MATRICS Consensus Cognitive Battery (MCCB), changes in local brain activity (functional magnetic resonance imaging, fMRI), white matter integrity (diffusion tensor imaging, DTI), changes in laboratory examination indices changes and changes in psycho-behavioral and EEG index.
This is the first clinical trial combining tDCS with rTMS for the treatment of schizophrenia patients with predominantly negative symptoms. This study will provide solid evidence for the combination of tDCS with rTMS for the treatment of negative symptoms in schizophrenia. This study will also help to further explore the mechanisms of tDCS combined with rTMS for the treatment of negative symptoms in schizophrenia in terms of imaging and behavior.
详细描述
This study was designed as an interventional, double-blind, sham-controlled, randomized open-label trial. The main objective is to investigate whether tDCS combined with rTMS is effective in improving negative symptoms in patients with schizophrenia and whether it is superior to single physical therapy. We will also study the effects of tDCS combined with rTMS on blood biomarkers, brain imaging, EEG and psycho-behavioral aspects in patients with schizophrenia.
Schizophrenia patients with prominent negative symptoms who met the inclusion criteria were randomly assigned in a 1:1:1:1 ratio to the active tDCS stimulation combined with active rTMS stimulation, active rTMS stimulation combined with sham tDCS stimulation, and active tDCS stimulation combined with sham rTMS stimulation to sham tDCS stimulation combined with sham rTMS stimulation. General information such as age, gender and marital status were matched between the different groups.
Firstly, a well-trained team is involved in the enrollment process, including a senior psychiatrist, two research nurses, two master students working full-time, and 20 psychiatrists who were actively referring patients for scientific research. Secondly, by giving a more elaborate explanation of the study goals, including the pros and cons, to both patients and their guardians they now better understand the background and possible relevance of the study.
The study population will include 120 patients with schizophrenia mainly with negative symptoms recruited from the inpatient departments of Tianjin Anding Hospital. Schizophrenia is diagnosed according to the Diagnostic and Statistical Manual of Mental Disorder, 5th Edition (DSM-5). All patients are stabilized with no changes in their treatment over the past 1 month prior to their inclusion.
For all patients, clinicians assess the subject's eligibility and provide to each subject and to the patient's legal representative comprehensive verbal and written information regarding the objectives and procedures of the study as well as the possible risks. A signed informed consent is obtained from each participant and/or legal representative for schizophrenia prior to undertaking any study-related procedure. Schizophrenia who do not wish to take part in the study will continue to undergo treatment as usual.
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)
入排标准
- 年龄范围
- 18 Years 至 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Meets Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) diagnostic classification criteria for schizophrenia.
- •Age 18-60 years old, gender is not limited.
- •Predominantly negative symptoms (PANSS-negative symptom score≥20; or PANSS negative scores are higher than positive scores).
- •Stable psychiatric symptoms (negative symptoms, positive symptoms) for more than 4 weeks or more.
- •No adjustment in the type or dose of antipsychotics taken in the past 1 months and in the next 1 months
- •Patients and Guardians agree to participate in this study and sign an informed consent form.
排除标准
- •Patients with severe physical illness, infectious diseases and immune system diseases, severe neurological diseases, mental retardation or organic brain diseases.
- •Pregnant or lactating women.
- •Other brain stimulation treatment (ECT, MECT, etc) within past 3 months.
- •History of previous seizures.
- •Those evaluated as unsuitable for tDCS and rTMS and those who do not cooperate with treatment.
- •Additional exclusion criteria for patients participating in the MRI scanning Participants have to fill out a detailed questionnaire covering safety aspects in relation to research in a 3 Tesla magnetic field and MRI environment. These criteria are:
- •MRI incompatible implants in the body (such as cochlear implant, insulin pump, pace maker or other metal implants).
- •Any risk of having metal particles in the eye, due to manual work without proper eye protections.
- •Tattoos containing red pigments.
- •Claustrophobia.
- •The refusal to be informed of structural brain abnormalities that could be detected during the experiment.
研究组 & 干预措施
tDCS active stimulation combined with rTMS sham stimulation group
1
干预措施: tDCS active stimulation combined with rTMS sham stimulation (Device)
rTMS active stimulation combined with tDCS sham stimulation group
2
干预措施: rTMS active stimulation combined with tDCS sham stimulation (Device)
tDCS active stimulation combined with rTMS active stimulation group
3
干预措施: tDCS active stimulation combined with rTMS active stimulation (Device)
tDCS sham stimulation combined with rTMS sham stimulation group
4
干预措施: tDCS sham stimulation combined with rTMS sham stimulation (Device)
结局指标
主要结局
Changes in the Scale for Assessment of Negative Symptoms (SANS)
时间窗: weeks 0, 2, 4, and 6
The primary clinical outcome was the overall severity of negative symptoms of psychosis, as measured by the Scale for Assessment of Negative Symptoms (SANS) at weeks 0(baseline), 2,4 and 6. And the changes between the four assessments were compared in order of time progression。 The Scale for Assessment of Negative Symptoms (SANS) contains 5 subscales, namely: flat or sluggish affect, poor thinking, lack of will, lack of interest or socialization, and attention deficit. The score range is 0-120, and the total score reflects the severity of negative symptoms; the higher the score, the more severe the symptoms.
次要结局
- Changes in the Positive and Negative symptom scale (PANSS)(weeks 0, 2, 4, and 6)
- Changes in psycho-behavioral markers(weeks 0 and 4)
- MATRICS Consensus Cognitive Battery (MCCB)(weeks 0, 4, and 6)
- Changes in Gene and Protein markers(weeks 0 and 4)
- Changes in brain imaging markers(weeks 0 and 4)
- Changes in Event-related potentials markers(weeks 0 and 4)
研究者
Jie Li
Chief physician；professor
Tianjin Anding Hospital