Utilizing Changes in Human Brain Connectivity to Establish a Dose-response Relationship Involved in the Therapeutic Actions of Prefrontal Brain Stimulation on Depression Symptoms
试验速览
- 阶段
- 不适用
- 状态
- 进行中（未招募）
- 入组人数
- 100
- 试验地点
- 1
- 主要终点
- Change in resting state functional connectivity of the subgenual anterior cingulate cortex (sgACC) and the default mode network (DMN).
研究概览
简要总结
This study evaluates an accelerated schedule of theta-burst stimulation using a transcranial magnetic stimulation device for treatment-resistant depression. In a double-blind, randomized, sham-controlled fashion, half the participants will receive accelerated theta-burst stimulation while half will receive sham treatment.
详细描述
Repetitive transcranial magnetic stimulation (rTMS) is an established therapy for treatment-resistant depression. The approved method for treatment is 10Hz stimulation for 40 min over the left dorsolateral prefrontal cortex (L-DLPFC). This methodology has been effective in real world situations. The limitations of this approach include the duration of the treatment (approximately 40 minutes per treatment session, 5 days per week, for 4-8 weeks). Recently, we have pursued modifying the treatment parameters to reduce treatment times with an accelerated treatment paradigm with great preliminary success. This study aims to further study our accelerated protocol and examine changes in neuroimaging biomarkers.
Dr. Nolan Williams is the Principle Investigator on the grant associated for this study and so is listed as Study Director on the study record.
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
- 22 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or Female, between the ages of 22 and 65 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 interventions. 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 Major Depressive Disorder (MDD) and meets criteria for a Major Depressive Episode, 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 (MSM3).
- •MADRS score of ≥20 at screening (Visit 1).
- •Access to ongoing psychiatric care before and after completion of the study.
- •Access to clinical rTMS after study completion.
- •Must be on a stable antidepressant therapeutic regimen for 6 weeks prior to study enrollment and agree to continue this regimen throughout the study period.
- •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 throughout study duration.
- •Lifestyle considerations:
- •Abstain from becoming pregnant from the screening visit (Visit 1) until after the final study visit (Visit 9).
- •Continue usual intake patterns of caffeine- or xanthine-containing products (e.g., coffee, tea, cola drinks, and chocolate) without significant change for the duration of the study.
- •Abstain from alcohol for at least 24 hours before the start of each MRI and TMS session. Participants who use tobacco products will be informed that use will be allowed only in between intervention sessions.
排除标准
- •Primary psychiatric condition other than MDD requiring treatment except stable comorbid anxiety disorder
- •History of or current psychotic disorder or bipolar disorder
- •Severe borderline personality disorder.
- •Diagnosis of Intellectual Disability or Autism Spectrum Disorder
- •Current moderate or severe substance use disorder or demonstrating signs of acute substance withdrawal
- •Urine screening test positive for illicit substances
- •Active suicidal ideation (defined as an MSSI > 8) or a suicide attempt (as defined by the C-SSRS) within the past one year
- •Any history of ECT (greater than 8 sessions) without meeting responder criteria
- •Recent (within 4 weeks of any clinical effect) or concurrent use of 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, seizure disorder, subdural hematoma, multiple sclerosis, or history of significant head trauma
- •Untreated or insufficiently treated endocrine disorder.
- •Contraindication to receiving rTMS (e.g., metal in head, history of seizure, known brain lesion)
- •Contraindication to MRI (ferromagnetic metal in their body)
- •Treatment with another investigational drug or other intervention within the study period
- •Depth-adjusted aiTBS treatment dose > 65% maximum stimulator output (MSO)
- •Unstable symptoms between screening and baseline as defined by a ≥ 30% change in MADRS-S score.
- •Any other condition deemed by the PD to interfere with the study or increase risk to the participant
研究组 & 干预措施
Active TBS-DLPFC
The active group will receive theta-burst TMS stimulation.
干预措施: Active TBS-DLPFC (Device)
Sham TBS-DLPFC
The sham group will receive sham theta-burst TMS stimulation.
干预措施: Sham TBS-DLPFC (Device)
结局指标
主要结局
Change in resting state functional connectivity of the subgenual anterior cingulate cortex (sgACC) and the default mode network (DMN).
时间窗: At baseline (day 3) through immediate post-treatment follow up visit (day 8).
Assessment of functional connectivity of sgACC to the DMN using magnetic resonance imaging.
次要结局
- Relationship between clinical improvement and resting state functional connectivity between the sgACC and DMN in active vs. sham participants.(At baseline (day 3) and at immediate post-treatment follow up visit (day 8).)
- Relationship between acute mood state and resting state functional connectivity between the sgACC and DMN in active vs. sham participants.(At baseline (day 3) and at immediate post-treatment follow up visit (day 8).)
研究者
David Spiegel
Professor, Department of Psychiatry and Behavioral Sciences, Stanford University
Stanford University