Therapeutic Efficacy of Transcranial Magnetic Stimulation in Schizophrenia
2018年3月14日 更新者：Mark Halko、Beth Israel Deaconess Medical Center
Therapeutic Efficacy of Cerebellar Repetitive Transcranial Magnetic Stimulation in Patients With Schizophrenia
The aim of this study is to look at the effectiveness of repetitive transcranial magnetic stimulation (rTMS) as a therapeutic intervention for patients with schizophrenia.
The primary outcome is improvement in negative symptoms related to schizophrenia.
The investigators are focusing on negative symptoms given their greater resistance to pharmacological and other established therapies.
If the investigators trial were to show beneficial effects, its clinical significance would be great.
研究概览
详细说明
This study builds on the results of a previous phase 1, single-site study in which we demonstrated the safety of image-guided theta burst stimulation (TBS) form of rTMS over the cerebellar vermis (Demirtas-Tatlidede et al., 2010) in eigh patients with schizophrenia.
The primary goal of the present study is to assess efficacy of iTBS to the cerebellar vermis on positive and negative symptoms of schizophrenia. A second, added goal is to investigate the mechanisms of the expected clinical improvement.
Schizophrenia is a leading cause of mental disability and current treatments still remain only partially successful for many patients. Our underlying hypothesis is that modulation of the cerebellar vermis may enhance activity of the neural systems that sub-serve cognition and emotion, reestablish the disturbed cerebellar regulation in schizophrenic patients, and produce clinical improvement.
研究类型
介入性
注册 (实际的)
22
阶段
- 不适用
联系人和位置
本节提供了进行研究的人员的详细联系信息，以及有关进行该研究的地点的信息。
学习地点
-
-
Massachusetts
-
Boston、Massachusetts、美国、02134
- Beth Israel Deaconess Medical Center
-
-
参与标准
研究人员寻找符合特定描述的人，称为资格标准。这些标准的一些例子是一个人的一般健康状况或先前的治疗。
资格标准
适合学习的年龄
18年 至 65年 (成人、年长者)
接受健康志愿者
不
有资格学习的性别
全部
描述
Inclusion Criteria:
- Age between 18-65 years
- Diagnosis of schizophrenia according to DSM-IV criteria (Diagnostic and Statistical Manual) by a board-certified psychiatrist
Exclusion Criteria:
- Preexisting or progressive neurological disorders
- Prior neurological procedures
- Previous head injury
- Change in antipsychotic medication during the last 4 weeks
- Been an inpatient in a psychiatry clinic within the last month
- Any other axis 1 diagnosis
- Patients may not be actively enrolled in a separate intervention study
- Patients unable to undergo a brain MRI
- Any unstable medical condition
- History of seizures, diagnosis of epilepsy, history of abnormal (epileptiform_ EEG, or family history of treatment resistant epilepsy
- Possible pregnancy. All female participants of child bearing age are required to have a pregnancy test.
- Any metal in the brain, skull, or elsewhere unless approved by the responsible MD
- Any medical devices (ie. cardiac pacemaker, deep brain stimulator, medication infusion pump, cochlear implant, vagal nerve stimulator) unless otherwise approved by the responsible MD
- Substance abuse (alcohol, amphetamines, cocaine, MDMA [methylenedioxymethamphetamine], ecstasy, PCP [phencyclidine], Angle dust) or dependence within the past six months
- No medication is an absolute exclusion from TMS. Medications will be reviewed by the responsible MD and a decision about inclusion will be made based on the following: the patient's past medical history, drug dose, history of recent medication changes or duration of treatment, and combination with other CNS (central nervous system) active drugs (the published TMS guidelines review of medications to be considered with TMS)
学习计划
本节提供研究计划的详细信息，包括研究的设计方式和研究的衡量标准。
研究是如何设计的？
设计细节
- 主要用途：治疗
- 分配：随机化
- 介入模型：并行分配
- 屏蔽：三倍
武器和干预
参与者组/臂 |
干预/治疗 |
|---|---|
|
有源比较器：Active rTMS
High frequency rTMS stimulation of the vermis(lobule VII) of the cerebellum.
|
intermittent Theta Burst (iTBS) pattern (20 trains of 10 bursts given with 8s intervals) will be applied at 80% of active motor threshold. Each participant will receive 600 pulses per session. Sham participants will undergo the same procedures as those in the active rTMS group.
其他名称：
|
|
假比较器：Sham rTMS
Sham rTMS to the vermis (lobule VII) of the cerebellum.
|
intermittent Theta Burst (iTBS) pattern (20 trains of 10 bursts given with 8s intervals) will be applied at 80% of active motor threshold. Each participant will receive 600 pulses per session. Sham participants will undergo the same procedures as those in the active rTMS group.
其他名称：
|
研究衡量的是什么？
主要结果指标
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
|
Change From Baseline on the Positive and Negative Syndrome Scale (PANSS) Positive Subscale
大体时间：Before treatment (baseline), last day of treatment (after 5 days of treatment), 1 and 3 weeks post treatment
|
Therapeutic efficacy was evaluated with the Positive and Negative Syndrome Scale (PANSS) Positive Subscale, a 7 item subscale measuring the presence/absence and severity of positive symptoms of schizophrenia.
The minimum score is 7 and the maximum score is 49, with higher values representing greater symptom severity.
Change from baseline on the PANSS Positive Subscale can range from -42 to +42; negative values represent an improvement in symptom severity, and positive values represent worsening symptom severity.
Therapeutic efficacy was assessed at baseline, after 5 days of treatment, 1 week post treatment, and 3 weeks post treatment.
|
Before treatment (baseline), last day of treatment (after 5 days of treatment), 1 and 3 weeks post treatment
|
|
Change From Baseline on the Positive and Negative Syndrome Scale (PANSS) Negative Subscale
大体时间：Before treatment (baseline), last day of treatment (after 5 days of treatment), 1 and 3 weeks post treatment
|
Therapeutic efficacy was evaluated with the Positive and Negative Syndrome Scale (PANSS) Negative Subscale, a 7 item subscale measuring the presence/absence and severity of negative symptoms of schizophrenia.
The minimum score is 7 and the maximum score is 49, with higher values representing greater symptom severity.
Change from baseline on the PANSS Negative Subscale can range from -42 to +42; negative values represent an improvement in symptom severity, and positive values represent worsening symptom severity.
Therapeutic efficacy was assessed at baseline, after 5 days of treatment, 1 week post treatment, and 3 weeks post treatment.
|
Before treatment (baseline), last day of treatment (after 5 days of treatment), 1 and 3 weeks post treatment
|
|
Change From Baseline on the Positive and Negative Syndrome Scale (PANSS) General Subscale
大体时间：Before treatment (baseline), last day of treatment (after 5 days of treatment), 1 and 3 weeks post treatment
|
Therapeutic efficacy was evaluated with the Positive and Negative Syndrome Scale (PANSS) General Subscale, a 16 item subscale measuring the presence/absence and severity of general psychopathology of schizophrenia.
The minimum score is 16 and the maximum score is 112, with higher values representing greater psychopathology severity.
Change from baseline on the PANSS General Subscale can range from -96 to +96; negative values represent an improvement in symptom severity, and positive values represent worsening symptom severity.
Therapeutic efficacy was assessed at baseline, after 5 days of treatment, 1 week post treatment, and 3 weeks post treatment.
|
Before treatment (baseline), last day of treatment (after 5 days of treatment), 1 and 3 weeks post treatment
|
|
Change From Baseline on the Clinical Global Impression (CGI) Severity of Illness
大体时间：Before treatment (baseline), last day of treatment (after 5 days of treatment), 1 and 3 weeks post treatment
|
Treatment response was evaluated with the Clinical Global Impressions (CGI) Scale, which is comprised of two companion one-item measures that use 7-point scales to evaluate severity of psychopathology and improvement from the initiation of treatment; each component is rated separately and the CGI does not yield a global score.
The CGI Severity of Illness is a 7-point subscale in which a clinician rates the severity of the patient's illness at the time of assessment.
Ratings range from 1 to 7 and higher values represent more severe psychopathology: 1 indicates a normal and not at all ill patient and 7 indicates among the most extremely ill patients.
Change from baseline on the CGI Severity of Illness subscale can range from -6 to +6, with negative values representing an improvement in psychopathology and positive values representing worsening psychopathology.
Severity of Illness was assessed at baseline, after 5 days of treatment, 1 week post treatment, and 3 weeks post treatment.
|
Before treatment (baseline), last day of treatment (after 5 days of treatment), 1 and 3 weeks post treatment
|
|
Clinical Global Impression (CGI) Global Improvement
大体时间：Last day of treatment (after 5 days of treatment), 1 and 3 weeks post treatment
|
Treatment response was evaluated with the Clinical Global Impressions (CGI) Scale, which is comprised of two companion one-item measures that use 7-point scales to evaluate severity of psychopathology and improvement from the initiation of treatment; each component is rated separately and the CGI does not yield a global score.
The CGI Global Improvement is a 7-point subscale in which a clinician assesses how much a patient's illness has changed compared to baseline.
Ratings range from 1 to 7, with 1 indicating very much improved and 7 indicating very much worse.
Change from baseline on the CGI Global Improvement subscale can range from -6 to +6, with negative values representing an improvement in psychopathology and positive values representing worsening psychopathology.
Global Improvement was assessed after 5 days of treatment, 1 week post treatment, and 3 weeks post treatment.
|
Last day of treatment (after 5 days of treatment), 1 and 3 weeks post treatment
|
次要结果测量
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
|
Change From Baseline on the Calgary Depression Scale for Schizophrenia
大体时间：Before treatment (baseline), last day of treatment (after 5 days of treatment), 1 and 3 weeks post treatment
|
The Calgary Depression Scale for Schizophrenia is a 9-item scale that assesses depressive symptoms in patients with schizophrenia.
Each item is rated separately and ratings range from 0 to 3. Higher values represent more severe depressive symptoms: 0 indicates an absent symptom and 3 indicates a severe symptom.
The overall Calgary Depression Scale score is computed by summing each item.
The total Calgary Depression Scale score ranges from 0 to 27, with higher values representing more severe depression in patients with schizophrenia.
Change from baseline on the Calgary Depression Scale can range from -27 to +27, with negative values representing an improvement in depressive symptoms and positive values representing worsening depressive symptom severity.
Depression was assessed at baseline, after 5 days of treatment, 1 week post treatment, and 3 weeks post treatment.
|
Before treatment (baseline), last day of treatment (after 5 days of treatment), 1 and 3 weeks post treatment
|
合作者和调查者
在这里您可以找到参与这项研究的人员和组织。
调查人员
- 首席研究员：Mark Halko, Ph.D.、Beth Israel Deaconess Medical Center
出版物和有用的链接
负责输入研究信息的人员自愿提供这些出版物。这些可能与研究有关。
一般刊物
- Pascual-Leone A, Rubio B, Pallardo F, Catala MD. Rapid-rate transcranial magnetic stimulation of left dorsolateral prefrontal cortex in drug-resistant depression. Lancet. 1996 Jul 27;348(9022):233-7. doi: 10.1016/s0140-6736(96)01219-6.
- Rossi S, Hallett M, Rossini PM, Pascual-Leone A; Safety of TMS Consensus Group. Safety, ethical considerations, and application guidelines for the use of transcranial magnetic stimulation in clinical practice and research. Clin Neurophysiol. 2009 Dec;120(12):2008-2039. doi: 10.1016/j.clinph.2009.08.016. Epub 2009 Oct 14.
- Demirtas-Tatlidede A, Freitas C, Cromer JR, Safar L, Ongur D, Stone WS, Seidman LJ, Schmahmann JD, Pascual-Leone A. Safety and proof of principle study of cerebellar vermal theta burst stimulation in refractory schizophrenia. Schizophr Res. 2010 Dec;124(1-3):91-100. doi: 10.1016/j.schres.2010.08.015.
- Batini C, Buisseret-Delmas C, Corvisier J, Hardy O, Jassik-Gerschenfeld D. Brain stem nuclei giving fibers to lobules VI and VII of the cerebellar vermis. Brain Res. 1978 Sep 22;153(2):241-61. doi: 10.1016/0006-8993(78)90405-5.
- Demirtas-Tatlidede A, Freitas C, Pascual-Leone A, Schmahmann JD. Modulatory effects of theta burst stimulation on cerebellar nonsomatic functions. Cerebellum. 2011 Sep;10(3):495-503. doi: 10.1007/s12311-010-0230-5.
- Fregni F, Boggio PS, Valle AC, Rocha RR, Duarte J, Ferreira MJ, Wagner T, Fecteau S, Rigonatti SP, Riberto M, Freedman SD, Pascual-Leone A. A sham-controlled trial of a 5-day course of repetitive transcranial magnetic stimulation of the unaffected hemisphere in stroke patients. Stroke. 2006 Aug;37(8):2115-22. doi: 10.1161/01.STR.0000231390.58967.6b. Epub 2006 Jun 29.
- Fregni F, Thome-Souza S, Bermpohl F, Marcolin MA, Herzog A, Pascual-Leone A, Valente KD. Antiepileptic effects of repetitive transcranial magnetic stimulation in patients with cortical malformations: an EEG and clinical study. Stereotact Funct Neurosurg. 2005;83(2-3):57-62. doi: 10.1159/000086674. Epub 2005 Jun 30.
- Fregni F, Freedman S, Pascual-Leone A. Recent advances in the treatment of chronic pain with non-invasive brain stimulation techniques. Lancet Neurol. 2007 Feb;6(2):188-91. doi: 10.1016/S1474-4422(07)70032-7.
- George MS, Wassermann EM, Williams WA, Callahan A, Ketter TA, Basser P, Hallett M, Post RM. Daily repetitive transcranial magnetic stimulation (rTMS) improves mood in depression. Neuroreport. 1995 Oct 2;6(14):1853-6. doi: 10.1097/00001756-199510020-00008.
- George MS, Nahas Z, Kozel FA, Goldman J, Molloy M, Oliver N. Improvement of depression following transcranial magnetic stimulation. Curr Psychiatry Rep. 1999 Dec;1(2):114-24. doi: 10.1007/s11920-999-0020-2.
- Gershon AA, Dannon PN, Grunhaus L. Transcranial magnetic stimulation in the treatment of depression. Am J Psychiatry. 2003 May;160(5):835-45. doi: 10.1176/appi.ajp.160.5.835.
- Hajak G, Marienhagen J, Langguth B, Werner S, Binder H, Eichhammer P. High-frequency repetitive transcranial magnetic stimulation in schizophrenia: a combined treatment and neuroimaging study. Psychol Med. 2004 Oct;34(7):1157-63. doi: 10.1017/s0033291704002338.
- Hashimoto M, Ohtsuka K. Transcranial magnetic stimulation over the posterior cerebellum during visually guided saccades in man. Brain. 1995 Oct;118 ( Pt 5):1185-93. doi: 10.1093/brain/118.5.1185.
- Heath RG. Modulation of emotion with a brain pacemamer. Treatment for intractable psychiatric illness. J Nerv Ment Dis. 1977 Nov;165(5):300-17.
- Heath RG, Dempesy CW, Fontana CJ, Myers WA. Cerebellar stimulation: effects on septal region, hippocampus, and amygdala of cats and rats. Biol Psychiatry. 1978 Oct;13(5):501-29.
- Huber TJ, Schneider U, Rollnik J. Gender differences in the effect of repetitive transcranial magnetic stimulation in schizophrenia. Psychiatry Res. 2003 Aug 30;120(1):103-5. doi: 10.1016/s0165-1781(03)00170-7.
- Jardri R, Lucas B, Delevoye-Turrell Y, Delmaire C, Delion P, Thomas P, Goeb JL. An 11-year-old boy with drug-resistant schizophrenia treated with temporo-parietal rTMS. Mol Psychiatry. 2007 Apr;12(4):320. doi: 10.1038/sj.mp.4001968. No abstract available.
- Jin Y, Potkin SG, Kemp AS, Huerta ST, Alva G, Thai TM, Carreon D, Bunney WE Jr. Therapeutic effects of individualized alpha frequency transcranial magnetic stimulation (alphaTMS) on the negative symptoms of schizophrenia. Schizophr Bull. 2006 Jul;32(3):556-61. doi: 10.1093/schbul/sbj020. Epub 2005 Oct 27.
- Martin PI, Naeser MA, Theoret H, Tormos JM, Nicholas M, Kurland J, Fregni F, Seekins H, Doron K, Pascual-Leone A. Transcranial magnetic stimulation as a complementary treatment for aphasia. Semin Speech Lang. 2004 May;25(2):181-91. doi: 10.1055/s-2004-825654.
- Ohtsuka K, Enoki T. Transcranial magnetic stimulation over the posterior cerebellum during smooth pursuit eye movements in man. Brain. 1998 Mar;121 ( Pt 3):429-35. doi: 10.1093/brain/121.3.429.
- Papez JW. A proposed mechanism of emotion. 1937. J Neuropsychiatry Clin Neurosci. 1995 Winter;7(1):103-12. doi: 10.1176/jnp.7.1.103. No abstract available.
- Rollnik JD, Huber TJ, Mogk H, Siggelkow S, Kropp S, Dengler R, Emrich HM, Schneider U. High frequency repetitive transcranial magnetic stimulation (rTMS) of the dorsolateral prefrontal cortex in schizophrenic patients. Neuroreport. 2000 Dec 18;11(18):4013-5. doi: 10.1097/00001756-200012180-00022.
- Schmahmann JD. The role of the cerebellum in cognition and emotion: personal reflections since 1982 on the dysmetria of thought hypothesis, and its historical evolution from theory to therapy. Neuropsychol Rev. 2010 Sep;20(3):236-60. doi: 10.1007/s11065-010-9142-x. Epub 2010 Sep 7.
- Schutter DJ, van Honk J, d'Alfonso AA, Peper JS, Panksepp J. High frequency repetitive transcranial magnetic over the medial cerebellum induces a shift in the prefrontal electroencephalography gamma spectrum: a pilot study in humans. Neurosci Lett. 2003 Jan 16;336(2):73-6. doi: 10.1016/s0304-3940(02)01077-7.
有用的网址
研究记录日期
这些日期跟踪向 ClinicalTrials.gov 提交研究记录和摘要结果的进度。研究记录和报告的结果由国家医学图书馆 (NLM) 审查，以确保它们在发布到公共网站之前符合特定的质量控制标准。
研究主要日期
学习开始
2012年2月1日
初级完成 (实际的)
2015年11月1日
研究完成 (实际的)
2015年11月1日
研究注册日期
首次提交
2012年3月1日
首先提交符合 QC 标准的
2012年3月9日
首次发布 (估计)
2012年3月13日
研究记录更新
最后更新发布 (实际的)
2018年4月12日
上次提交的符合 QC 标准的更新
2018年3月14日
最后验证
2018年3月1日
更多信息
与本研究相关的术语
药物和器械信息、研究文件
研究美国 FDA 监管的药品
不
研究美国 FDA 监管的设备产品
不
在美国制造并从美国出口的产品
不
此信息直接从 clinicaltrials.gov 网站检索，没有任何更改。如果您有任何更改、删除或更新研究详细信息的请求，请联系 register@clinicaltrials.gov. clinicaltrials.gov 上实施更改，我们的网站上也会自动更新.