Treating Adolescent and Adult Tic Disorders With Transcranial Magnetic Stimulation
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 40
- 试验地点
- 1
- 主要终点
- To assess the safety and tolerability of repeated theta burst TMS administration in adolescents age 15 - 35 years with CTD.
研究概览
简要总结
This project investigates safety, tolerability, and efficacy signals of accelerated continuous theta burst stimulation (cTBS), a form of inhibitory repetitive transcranial magnetic stimulation (rTMS), for patients with Tourette Syndrome and chronic tic disorders (CTD). It integrates resting-state functional MRI (fMRI) to assess changes in brain circuits and neurophysiology. CTD are neurodevelopmental disorders marked by motor and/or vocal tics, associated with dysfunction in cortico-striato-thalamo-cortical (CSTC) networks, particularly the supplementary motor area (SMA), primary motor cortex (M1), and connected regions. While low-frequency rTMS has shown preliminary benefits in pediatric populations, circuit-targeted approaches remain relatively unexplored in children, adolescents and adults, leaving no consensus about optimal applications.
Participants will be randomized to receive 50 sessions of 1800 pulses of cTBS rTMS over two weeks, with five sessions/day targeting the SMA or M1. Assessments will include the Yale Global Tic Severity Scale (YGTSS) and MRI.
Aim 1 Determine if cTBS to the M1 can reduce CTD symptoms and normalize abnormal network connectivity within the Somato-Cognitive Action Network (SCAN).
Aim 2 Determine if cTBS to the SMA can reduce symptoms of CTD and normalize abnormal network connectivity within the Action Mode Network (AMN).
详细描述
For Aims 1 and 2, the investigators propose to test a protocol of accelerated inhibitory continuous theta burst stimulation (cTBS) targeting areas of tic-related hyperactivity as identified by functional MRI. Participants will be randomized by computerized list to either receive rTMS directed at the SMA or rTMS directed toward the M1. The investigators will examine data on tolerability, adverse events and early efficacy signals that could inform future, larger scale controlled trials for this indication in adolescents and young adults.
TMS: Our protocol consists of five treatments of inhibitory continuous TBS (cTBS) with the target intensity less than 100% to the SMA or M1 Thumb (as determined by random assignment) lasting five minutes delivered over the course of 10 days (2 weeks) for a total of 50 treatments.
For Aim 3, the investigators will utilize repeated brain MRI imaging pre- and post-TMS treatment within persons with CTD to gauge direction of effects. The investigators plan to observe functional network activity in presumed tic-related neural circuits in youth with CTD pre- and post-treatment. A within-person design also highlights a personalized approach to circuit-based therapeutics that can be explored for individual differences in neural and clinical responses.
MR Imaging Protocol: MRI scanning including T1-weighted anatomical and rs-fMRI will take place on a GE Discovery MR750 3 Tesla scanner. For the rs-fMRI scan, patients will be asked to undergo at least 2x 7 minute scans with eyes open and were observed by an MR technician to ensure wakefulness. All T1 and fMRI scans will be preprocessed using the fMRIprep, a standardized preprocessing pipeline which utilizes tools from the widely-used MRI processing software packages AFNI, ANTs, FreeSurfer, and FSL. T1 scans will be corrected for intensity nonuniformity, skull-stripped, and segmented for registration purposes, then resampled into MNI space. fMRI scans will be slice-time corrected and resampled back to their native space with headmotion correction, then registered and resampled to both T1 space and MNI space. Data analysis will be performed in AFNI, including denoising of fMRI data using nuisance regressors generated by fMRIprep including 12 motion parameters as well as CSF and white matter signals. The resulting residual signal will then be utilized to generate RSFC matrices from the Fisher transformed correlation to generate normalized Z statistics.
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
- None
入排标准
- 年龄范围
- 15 Years 至 35 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Outpatients
- •Ages 15 - 35 years old
- •Meets DSM-5 criteria for persistent (chronic) vocal/motor tic disorder or Tourette's syndrome with screening YGTSS score ≥ 20 (moderate or greater severity).
- •Moderate severity or intolerable side effects with at least one prior trial of an evidence-based anti-tic medication.
- •Stable on chronic psychotropic medications and/or therapy for 6 weeks prior to the study and agreeable to continue current treatments without change throughout the study.
- •Participants may continue to take medications and record daily usage throughout the study.
- •Capacity to provide informed assent or consent and parent or legal guardian able to provide consent for minors.
- •Ability to tolerate clinical study procedures.
- •Successfully complete the screening forms without any contraindications.
排除标准
- •Psychiatric: history of schizophrenia, bipolar disorder, substance /alcohol abuse disorder, current elevated suicide risk, prior psychosurgery.
- •Neurologic: severe neurocognitive disorder, seizure disorder, certain structural brain lesions (e.g., intracranial mass lesions, TBI, hydrocephalus, sequelae of meningitis, frank brain injury).
- •TMS contraindications: implanted device; presence of metal in the head, including eyes and ears (excluding dental implants); certain tics.
- •Subjects with an unstable physical, systemic, or metabolic disorder (e.g., unstable hypertension; malnutrition).
- •Females who are pregnant or nursing (as determined by a questionnaire and urine pregnancy test).
- •Inability to complete the research protocol as determined by the Principal Investigator.
研究组 & 干预措施
M1 (primary motor cortex)
Determine if cTBS to the M1 can reduce CTD symptoms and normalize abnormal network connectivity within the Somato-Cognitive Action Network (SCAN).
干预措施: cTBS (accelerated continuous theta burst stimulation) (Device)
SMA (supplementary motor area)
Determine if cTBS to the SMA can reduce symptoms of CTD and normalize abnormal network connectivity within the Action Mode Network (AMN).
干预措施: cTBS (accelerated continuous theta burst stimulation) (Device)
结局指标
主要结局
To assess the safety and tolerability of repeated theta burst TMS administration in adolescents age 15 - 35 years with CTD.
时间窗: All protocol visits (treatment days 1 - 10)
This study's primary aim is to determine the safety and tolerability of repeated TMS administration in adolescents and adults ages 15 - 35 years with DSM-5 confirmed CTD of moderate or greater severity. These will be determined by protocol completion rate from enrollment to final visit, and tabulation of the individual and summed frequencies of reported and identified adverse events observed from study enrollment to final visit.
次要结局
- To examine the possible efficacy of repeated TMS administration on CTD symptom severity at two different brain regions (M1 and SMA).(Screening, baseline, treatment day 5, treatment day 10, 1-week follow-up, 1-month follow-up)