A Prospective Study on the Efficacy and Safety of Transcranial Magnetic Stimulation Intervention for Treatment-Resistant Depression Guided by Positron Emission Tomography Imaging
试验速览
- 阶段
- 不适用
- 状态
- Enrolling By Invitation
- 发起方
- 入组人数
- 42
- 试验地点
- 1
- 主要终点
- Change in Suppression Index after treatment
研究概览
简要总结
Major depressive disorder (MDD) exhibit reduced visual motor perception, which affects prognosis. Metabolic substance changes and abnormal neural activity in the middle temporal visual area (MT) mediate this perceptual dysfunction. The main questions are: •there is no conclusive evidence of impairment of visual motion suppression in treatment-resistant depression (TRD); •it is unknown that functional abnormalities in the MT of TRD patients mediate possible changes in visual perception •lack of treatment for deficit in visual motor perception; •mechanisms behind the intervention process need to be explored. The goal of this clinical trial is to understand the function of visual motor perception in TRD, to validate the effect of the MT on visual motion perception and to explore the effectiveness of the intervention as well as the neurophysiological mechanisms.
This study was planned to •explore any differences in visual motor perception and function of MT between TRD and healthy controls; •analyze the influence of neurobiological changes in MT and related brain regions on visual motion perception; •investigate the effects of rTMS intervention in MT for treatment of impaired visual perception function in TRD; •studying potential therapeutic mechanisms by PET/MRI imaging.
Participants will divide into TRD group and HC group. Clinical symptoms, scales, visual perception suppression index, PET/MRI, electrophysiology and other clinical data were collected at baseline for both two groups. TRD group received high-frequency rTMS stimulation targeting the MT. Besides, psychological scales, visual suppression index, PET/MRI, electrophysiology and other clinical data were collected during the intervention and after treatment.
The researchers will •compare the differences in visual perceptual function and neurobiological characteristics between the TRD group and the HC group in baseline; •analyze the impact of MT and related brain regions in visual motion perception; •compare the suppression index before and after intervention in TRD to discuss the feasibility of rTMS stimulation targeting the MT to improve visual motion perception abnormalities；•utilize the changes in clinical data of PET/MRI and electrophysiology before and after the treatment of TRD group to explore the possible underlying mechanisms during the treatment process.
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)
入排标准
- 年龄范围
- 18 Years 至 45 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Receive two or more adequate doses and courses of antidepressant drugs in different mechanisms that were not effective and had been stable for more than 6 weeks on antidepressant medication prior to enrollment, with non-responsiveness defined as a decrease in HAMD-24 score of <50%.
- •24-item Hamilton Depression Scale (HAMD-24) ≥
- •Normal or corrected to normal vision.
- •Ability to complete spatial suppression psychophysical experiment.
- •education background above the college degree.
- •Age 18-45 years, regardless of gender.
- •Right-handedness.
- •Han Chinese.
- •Signed a written informed consent, willing to participate in the study and be evaluated.
排除标准
- •Co-morbid other mental disorders, including: schizophrenia, mental retardation, substance dependence, etc.
- •Patients with metal objects in the body or with other contraindications to PET-MRI scanning
- •Patients with severe or unstable somatic diseases
- •Women during pregnancy or lactation, and women of childbearing age with positive urine HCG test results during the screening period
- •Benzodiazepines were taken during the experimental period
- •Other conditions that, in the opinion of the investigator, exist that make participation in this clinical trial inappropriate.
结局指标
主要结局
Change in Suppression Index after treatment
时间窗: 2 weeks
Suppression Index (SI) defined as the difference of log10 thresholds for large versus small stimuli of gratings, is able to quantify the suppression strength. The higher the numerical value, the more severe the visual motor perception deficit.
Hamilton Depression Scale (24-items) Total Score Change
时间窗: 2 weeks
The Hamilton Depression Scale (24-items), is a 24 item diagnostic questionnaire used to measure the severity of depressive episodes in patients with mood disorders. It's considered the gold standard for rating depression severity and used frequently in clinical trials. Higher HAM-D24 score indicates more severe depression, and each item yields a score of 0 to 4. The higher scores representing more severe levels of depression. Remission is defined as HAM-D24 ≤8. A reduction of 50% or more in total score from Baseline indicates clinical response.
Change in synaptic density using positron emission tomography/magnetic resonance imaging
时间窗: 2 weeks
Positron emission tomography/magnetic resonance imaging (PET/MRI) is a fusion of PET and MRI, which integrates pathophysiological changes with morphological structure. Research using PET/MRI in major depression has shown that there are alterations in the snyaptic density of certain brain regions in people with the condition and synaptic dysfunction in the dorsolateral prefrontal cortex may have implications for the downstream organization of functional networks. The SV2A radioligand \[11C\]UCB-H can examine snyaptic density in human brain. And brain structure, function connectivity and spectrum of metabolic substances can be measured by MRI. Overall, PET/MRI has advantages for the diagnosis of major depression and the evaluation of treatment effects.
次要结局
- Change in Suppression Index after treatment(6 weeks)
- Change in the score of Visual Analog Scale (VAS)(6 weeks)
- Hamilton Depression Scale (24-items) Total Score Change(6 weeks)
- Change in the Clinically Useful Depression Outcome Scale-Mixed Subscale score(Baseline)
- Change in electroencephalogram(6 weeks)
- Change in the TMS-EEG data(2 weeks)
- Change in the score of Motor Agitation and Retardation Scale(6 weeks)
- Change in the rate of Beck Scale of Suicidal Ideation score(6 weeks)
- Change in the rate of Hamilton Anxiety Scale score(6 weeks)
- Change in the score of THINC-it(6 weeks)
- IL-6 level(6 weeks)
- the Chinese version of the Snaith-Hamilton Pleasure Scale(6 weeks)
- Change in the Laukes Emotional Intensity Scale score(6 weeks)