A Multi-Site, Randomized, Double-Blind Trial Assessing The Effects of SAINT® Neuromodulation System on Explicit and Implicit Suicidal Cognition
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 发起方
- 入组人数
- 2
- 试验地点
- 4
- 主要终点
- Change in the neural network underlying Explicit Suicidal Cognition (ESC) as measured by resting state functional connectivity changes in subgenual anterior cingulate (sgACC) and the default mode network (DMN).
研究概览
简要总结
This multi-site, double-blind, randomized, sham-controlled mechanistic trial aims to test the effects of Magnus Neuromodulation System (MNS) with Stanford Accelerated Intermittent Neuromodulation Therapy (SAINT®) Technology on the neural circuitry of suicidal cognitions in psychiatrically hospitalized patients with Major Depressive Disorder (MDD) and active suicidal ideation (SI). This will be accomplished by applying the MNS with SAINT to a customized target within the left dorsolateral prefrontal cortex (L-DLPFC) identified with fMRI for five consecutive days and measuring resting-state functional connectivity (RS FC) between the subgenual anterior cingulate cortex (sgACC) and the default mode network (DMN) at baseline and immediate-post visit. The relationship between changes in RS FC and changes in both Explicit and Implicit Suicidal Cognitions (ESC and ISC, respectively) will be determined. This study will also determine the relationship between changes in RS FC in neural networks underlying mediators of suicidal cognitions and changes in such mediators with active versus sham SAINT.
详细描述
This multi-site, double-blind, randomized, sham-controlled mechanistic trial aims to test the effects of Magnus Neuromodulation System (MNS) with Stanford Accelerated Intermittent Neuromodulation Therapy (SAINT®) Technology on the neural circuitry of suicidal cognitions in psychiatrically hospitalized patients with Major Depressive Disorder (MDD) and active suicidal ideation (SI). This will be accomplished by applying the MNS with SAINT protocol (10 applications per day to a customized target within the left dorsolateral prefrontal cortex (L-DLPFC) identified with fMRI for five consecutive days) and measuring resting-state functional connectivity (RS FC) between the subgenual anterior cingulate cortex (sgACC) and the default mode network (DMN) at baseline and immediate-post visit. The relationship between changes in RS FC and changes in both Explicit and Implicit Suicidal Cognitions (ESC and ISC, respectively) will be determined. This study will also determine the relationship between changes in RS FC in neural networks underlying mediators of suicidal cognitions and changes in such mediators (i.e., depression, hopelessness, anhedonia) with active versus sham SAINT.
The mechanistic hypothesis is that active SAINT modulates RS FC underlying ESC (sgACC-DMN) and ISC (DLPFC-ACC) and that these changes in connectivity will correlate with reductions in ESC and ISC, respectively. MDD with current Major Depressive Episode will be defined according to DSM-5 criteria, and active SI will be defined by a baseline modified Scale for Suicide Ideation (M-SSI) score ≥ 9.
The primary objective is to determine if active versus sham SAINT aiTBS applied to the left dorsolateral prefrontal cortex (L-DLPFC)-subgenual anterior cingulate cortex (sgACC) is effective in modulating neural networks underlying explicit suicidal cognition (ESC) in psychiatric inpatients.
The secondary objective is to determine if active versus sham SAINT aiTBS applied to the L-DLPFC-sgACC is effective in modulating neural networks underlying implicit suicidal cognition (ISC) in psychiatric inpatients.
The tertiary objective is to determine if active versus sham SAINT aiTBS applied to the L-DLPFC-sgACC is effective in modulating neural networks underlying mediators of suicidal cognitions such as depression, hopelessness, and anhedonia.
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 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Adults of all genders between the ages of 18 and 75 years at the time of screening.
- •Able to read, understand, and provide written, dated informed consent prior to screening.
- •Proficiency in English sufficient to complete questionnaires / follow instructions during fMRI assessments and aiTBS treatments. Stated willingness to comply with all study procedures, including availability for the duration of the study, and to communicate with study personnel about adverse events and other clinically important information.
- •Currently diagnosed with either Major Depressive Disorder (MDD) and meets criteria for a current Major Depressive Episode (MDE) according to the criteria defined in the Diagnosis and Statistical Manual of Mental Disorders, Fifth Edition, Text Revision (DSM-5).
- •Medical records confirming a history of moderate to severe treatment-resistance as defined by a score of 7-14 on the Maudsley Staging Method (MSM).
- •Endorses clinically significant explicit suicidal cognitions (score ≥ 9 on the M-SSI and score ≥ 6 on the BSS self-report) at screening.
- •MADRS score of >/=20 at screening (visit 1).
- •rTMS/iTBS naive.
- •Access to ongoing psychiatric care before and after completion of the study.
- •Access to clinical rTMS after hospital discharge.
- •In good general health, as evidenced by medical history.
- •For females of reproductive potential: use of highly effective contraception for at least 1 month prior to screening and agreement to use such a method during study participation.
- •Agreement to adhere to Lifestyle considerations:
- •Abstain from becoming pregnant from the screening visit (Visit 1) until after the final study visit (Visit 9).
- •Abstain from caffeine- or xanthine-containing products (e.g., coffee, tea, cola drinks, and chocolate) for 3 hours before the start of each dosing session until after the final TMS session.
- •Abstain from alcohol for 24 hours before the start of each dosing session until after collection of the final MRI.
- •Participants who use tobacco products will be instructed that use of cigarettes will not be allowed during the trial.
排除标准
- •Females who are pregnant or planning to become pregnant during the course of the study or any female that is breastfeeding
- •The presence or diagnosis of prominent anxiety disorder, personality disorder, or dysthymia in which in the Investigator's opinion is predominant to MDD
- •Depressed mood/dysphoria as a result of an illness other than MDD (e.g. gender dysphoria)
- •Current severe insomnia (must sleep a minimum of 5 hours each night before stimulation)
- •Current mania or psychosis
- •Bipolar Affective Disorder I and primary psychotic disorders.
- •Autism Spectrum disorder or Intellectual Disability
- •A diagnosis of obsessive-compulsive disorder (OCD)
- •Current moderate or severe substance use disorder or demonstrating signs of acute substance withdrawal.
- •Urine screening test positive for illicit substances.
- •Any history of ECT (greater than 8 sessions) without meeting responder criteria
- •No recent (during the current depressive episode) or concurrent use of a rapid acting antidepressant agent (i.e., ketamine or a course of ECT).
- •History of significant neurologic disease, including dementia, Parkinson's or Huntington's disease, brain tumor, unexpected seizure/epilepsy disorder, subdural hematoma, multiple sclerosis, or history of significant head trauma.
- •Untreated or insufficiently treated endocrine disorder.
- •Contraindications to receiving rTMS (e.g., metal in head, history of seizure, known brain lesion)
- •Contraindications to MRI (ferromagnetic metal in their body).
- •Any current or past history of any physical condition which in the investigator's opinion might put the subject at risk or interfere with study results interpretation.
- •Treatment with another investigational drug or other intervention within the study period.
- •Depth-adjusted SAINT® treatment dose > 65% maximum stimulator output (MSO)
- •Any other condition deemed by the PI to interfere with the study or increase risk to the participant.
研究组 & 干预措施
SAINT stimulation
Active SAINT stimulation will be applied to the left dorsolateral prefrontal cortex (DLPFC)
干预措施: Active SAINT Stimulation (Device)
Sham stimulation
Sham (non-active) stimulation will be applied to the left dorsolateral prefrontal cortex (DLPFC)
干预措施: Sham SAINT Stimulation (Device)
结局指标
主要结局
Change in the neural network underlying Explicit Suicidal Cognition (ESC) as measured by resting state functional connectivity changes in subgenual anterior cingulate (sgACC) and the default mode network (DMN).
时间窗: At baseline (day 0) and at post-inpatient treatment completion (day 2-7)
We will assess resting state functional connectivity between sgACC and the DMN and within the DMN using magnetic resonance imaging.
次要结局
- Change in the neural network underlying Implicit Suicidal Cognition (ISC) as measured by resting state functional connectivity changes in dorsolateral prefrontal cortex (DLPFC) and the anterior cingulate cortex (ACC).(At baseline (day 0) and at post-inpatient treatment completion (day 2-7))