Overcoming Psychomotor Slowing in Psychosis (OCoPS-P): a 3-week, Randomized, Double-blind, Placebo-controlled Trial of add-on Repetitive Transcranial Magnetic Stimulation for Psychomotor Slowing in Psychosis
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 103
- 试验地点
- 1
- 主要终点
- Change in Salpetriere Retardation Rating Scale (SSRS) from baseline
研究概览
简要总结
Psychomotor slowing is a major problem in psychosis. Aberrant function of the cerebral motor system is linked to psychomotor slowing in patients, particularly resting state hyperactivity in premotor cortices. A previous clinical trial indicated that inhibitory stimulation of the premotor cortex would reduce psychomotor slowing. The current study is further exploring this effect in a randomized, placebo-controlled, double-blind design with three arms of transcranial magnetic stimulation and measures of brain imaging and physiology prior to and after the intervention.
详细描述
As psychomotor slowing is a major problem in schizophrenia, contributing to poor functional outcome, and as no current treatment is effectively targeting psychomotor slowing, this study seeks to test noninvasive brain stimulation to overcome psychomotor slowing. Previous studies documented an aberrant increase of neural activity within the supplementary motor area (SMA) in patients with schizophrenia who had psychomotor slowing. Furthermore, a pilot study in major depression and schizophrenia indicated that inhibitory 1 Hz repetitive transcranial magnetic stimulation (rTMS) would improve psychomotor slowing in 82% of the participants. While this is encouraging, further evidence is needed to 1) replicate the clinical effect of 1 Hz rTMS on the SMA in schizophrenia, 2) to test against sham stimulation, facilitatory stimulation and no intervention, and 3) to test the effects of rTMS on the neural circuitry. Therefore, OCoPS includes more patients, more treatment arms, and more outcome variables than the first pilot trial.
Here we will enroll 88 patients with schizophrenia spectrum disorders and severe psychomotor slowing according to a standard rating scale. Subjects will be randomized to four arms, three of which are double blinded.
three weeks of daily rTMS over the SMA will be delivered. The first group receives inhibitory 1 Hz rTMS, the second group receives facilitatory intermittent theta burst stimulation (iTBS), and the third group receives sham stimulation with a placebo-coil. The fourth group will have no rTMS during the first three weeks, but will repeat the baseline measures after three weeks and then enter a treatment with 1Hz rTMS for three weeks. Outcome measures include the Salpetriere Retardation Rating Scale, observer ratings of motor behavior as well as measures of functioning. After the interventions, follow-up visits are planned at week 6 and week 24.
Finally, at baseline and after the rTMS course, patients will undergo MRI scanning for structural and functional alterations of the cerebral motor system.
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
Participants will not know the stimulation protocol, neither will the outcome assessor or the mental health care provider know the protocol applied
入排标准
- 年龄范围
- 18 Years 至 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Right-handed subjects
- •Ability and willingness to participate in the study
- •Ability to provide written informed consent
- •Informed Consent as documented by signature
- •Schizophrenia spectrum disorder according to diagnostic and statistical manual version 5 (DSM-5) criteria with current psychomotor slowing according to the Salpetriere Retardation Rating Scale (SRRS), score >= 15
排除标准
- •Substance abuse or dependence other than nicotine
- •Past or current medical or neurological condition associated with impaired or aberrant movement, such as brain tumors, stroke, M. Parkinson, M. Huntington, dystonia, or severe head trauma with subsequent loss of consciousness.
- •Epilepsy or other convulsions
- •History of any hearing problems or ringing in the ears
- •Standard exclusion criteria for MRI scanning and TMS; e.g. metal implants, claustrophobia
- •Patients only: any TMS treatment in the past 3 months
- •Women who are pregnant or breast feeding,
- •Intention to become pregnant during the course of the study,
- •Female participants who are surgically sterilised / hysterectomised or post-menopausal for longer than 2 years are not considered as being of child bearing potential.
- •Previous enrolment into the current study,
- •Enrolment of the investigator, his/her family members, employees and other dependent persons
- •Controls only: history of any psychiatric disorder or first-degree relatives with schizophrenia spectrum disorders.
研究组 & 干预措施
Inhibitory repetitive transcranial magnetic stimulation (rTMS)
1 Hz stimulation of 17 mins over the supplementary motor area (SMA), 1000 pulses at 110% resting motor threshold intensity total of 15 sessions in 3 weeks
干预措施: 1 Hz rTMS (Device)
Facilitatory intermittent theta burst stimulation (iTBS)
Intermittent theta burst stimulation of 50 Hz over the supplementary motor area (SMA) with 600 pulses in 2 sec trains every 10 seconds for 190 seconds total. Two iTBS stimulations will be administered with 15 mins pause in between.
total of 15 sessions in 3 weeks
干预措施: iTBS (Device)
Placebo
1 Hz stimulation of 17 mins over the supplementary motor area (SMA) without any magnetic emission using a placebo-coil that looks identical and makes identical sounds as the real TMS coil total of 15 sessions in 3 weeks
干预措施: Placebo (Drug)
结局指标
主要结局
Change in Salpetriere Retardation Rating Scale (SSRS) from baseline
时间窗: Week 3, week 6, week 24
Change in the Salpetriere Retardation Rating Scale (SRRS) from baseline; the total score of 15 items is used, ranging 0-60 with higher scores indicating worse outcome
Proportion of responders at week 3
时间窗: Week 3
Proportion of participants with \>30% reduction from baseline in the Salpetriere Retardation Rating Scale (SRRS)
次要结局
- Change in negative symptoms from baseline(Week 3, week 6, week 24)
- Change in psychosis severity from baseline(Week 3, week 6, week 24)
- Change in physical activity self report from baseline(Week 3, week 6, week 24)
- Change in objectively measured physical activity from baseline(Week 3, week 6, week 24)
- Change in dexterity from baseline(Week 3, week 6, week 24)
- Change in cortical excitability of the motor cortex from baseline(Week 3, week 6, week 24)
- Change in social and community functioning(Week 3, week 6, week 24)
- Change in catatonia severity from baseline to week 3(Week 3, week 6, week 24)
- Change in functional capacity(Week 3, week 6, week 24)
- Change in functional connectivity(Week 3)
- Change in resting state cerebral perfusion(Week 3)