TICS: Transcranial Magnetic Stimulation for Intervening in Children With Tourette's Syndrome
试验速览
- 阶段
- 不适用
- 入组人数
- 50
- 试验地点
- 1
- 主要终点
- Yale Global Tic Severity Scale Total Tic score (YGTSS)
研究概览
简要总结
Tourette's Syndrome (TS) is characterized by repetitive movements and vocalizations called tics. Due to the suffering caused by TS, children and adolescents often require treatment for their tics. The investigators' research focuses on developing novel repetitive transcranial magnetic stimulation (rTMS) interventions for child and adolescent neuropsychiatric disorders. In this project, the investigators will determine the effect of pairing 3 weeks of rTMS and HRT on tic severity and plasticity as indexed by supplementary motor area (SMA) y-aminobutyric acid (GABA) concentration and functional connectivity of the SMA to the primary motor cortex (M1) in children and adolescents with TS.
Children (N = 50, 6-18 years) with TS will be randomized to either a (1) rTMS+HRT arm, or (2) sham rTMS+HRT. Outcome measures will examine tic severity (primary), brain chemistry and function (secondary) at baseline and then at week 7. The investigators' proposed aims are:
(Aim 1) To determine the effect of paired rTMS and HRT on tic severity as measured by the Yale Global Tic Severity Scale (YGTSS) by comparing it to sham rTMS + HRT.
1-1: The investigators hypothesize that tic severity will decrease from baseline to post-treatment.
1-2: The investigators also hypothesize that the reduction in tic severity will be greater in the paired treatment group (rTMS+HRT > Sham rTMS+HRT).
(Aim 2) To determine the effect of paired rTMS and HRT on brain plasticity compared to sham rTMS + HRT.
2-1: The investigators hypothesize that patients treated with the paired rTMS and HRT will have a greater increase in GABA concentration comparted to sham and HRT.
2-2: The investigators also hypothesize that functional connectivity between the SMA and M1 will be greater with paired treatment (rTMS+HRT > Sham rTMS+HRT).
详细描述
Tourette's Syndrome (TS) is characterized by repetitive movements and vocalizations called tics. Due to the suffering caused by TS, children and adolescents often require treatment for their tics. Tic severity predicts poor outcomes across physical, psychological, and cognitive domains in youth. Current treatments for TS remain limited in scope and efficacy. Atypical antipsychotics are often used and for many patients have an unacceptable side effect burden. Behavioral treatments, like habit reversal therapy (HRT), show promise and are safe, but are predicated on a certain level of brain maturation to execute.
The investigators' research focuses on developing novel repetitive transcranial magnetic stimulation (rTMS) interventions for child and adolescent neuropsychiatric disorders. Plasticity, precision, and pairing are key considerations in this process. In this project, the investigators will determine the effect of pairing 3 weeks of rTMS and HRT on tic severity and plasticity as indexed by supplementary motor area (SMA) y-aminobutyric acid (GABA) concentration and functional connectivity of the SMA to the primary motor cortex (M1) in children and adolescents with TS. The investigators will use functional magnetic resonance imaging (fMRI) and robot controlled rTMS to precisely target the SMA. The investigators believe this pairing will provide improved relief by inducing plasticity to retrain the brain to be better at suppressing tics at an earlier age than usually expected.
Children (N = 50, 6-18 years) with TS will be randomized to either a (1) rTMS+HRT arm, or (2) sham rTMS+HRT. Outcome measures will examine tic severity (primary), brain chemistry and function (secondary) at baseline and then at week 7. The investigators' proposed aims are:
(Aim 1) To determine the effect of paired rTMS and HRT on tic severity as measured by the Yale Global Tic Severity Scale (YGTSS) by comparing it to sham rTMS + HRT.
1-1: The investigators hypothesize that tic severity will decrease from baseline to post-treatment.
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
- Double (Participant, Outcomes Assessor)
盲法说明
Eligible subjects will be randomly assigned to receive one of the two treatment regimens in a 1:1 ratio. Dr. Nettel-Aguirre will generate the sequence with random sized blocks of 2,4 and 6 and use the REDCap randomization module for recruiters to access the allocation for the subjects. The algorithm will stratify each by sex and age group (6-10, 11-14, 15-18 years). Dr. Zewdie will set up the rTMS accordingly for active or sham delivery. Participants and their parents will be blind to group status regarding sham vs. active rTMS. Dr. Wilcox, and all raters responsible for clinical evaluation under Dr. Wilcox's supervision, will also be blinded to group status.
入排标准
- 年龄范围
- 6 Years 至 18 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnosis of Tourette's syndrome
- •IQ greater than 80
- •English fluency (to enable assent and consent).
排除标准
- •Diagnosis of mania or schizophrenia
- •Impediments to TMS or MRI.
研究组 & 干预措施
rTMS + CBIT
Repetitive transcranial magnetic stimulation (rTMS) and Comprehensive Behavioural Intervention for Tics (CBIT)
干预措施: Sham rTMS + CBIT (Behavioral)
rTMS + CBIT
Repetitive transcranial magnetic stimulation (rTMS) and Comprehensive Behavioural Intervention for Tics (CBIT)
干预措施: rTMS + CBIT (Device)
Sham rTMS + CBIT
Sham repetitive transcranial magnetic stimulation (rTMS) and Comprehensive Behavioural Intervention for Tics (CBIT)
干预措施: Sham rTMS + CBIT (Behavioral)
结局指标
主要结局
Yale Global Tic Severity Scale Total Tic score (YGTSS)
时间窗: Baseline to week 7
30% reduction in Yale Global Tic Severity Scale Total Tic score (YGTSS) (\~9 point reduction). A higher score on all scales suggests a more severe tics. The YGTSS provides two tic severity scores: 1. Total Motor (0 to 25) 2. Total Phonic (0 to 25) These are summed to form the Total Tic Severity Score (0 to 50). This is the measure for the primary outcome variable. There is also the separate Impairment Dimension Score (0 to 50). The total score is hence 0 to 100 (sum of Total Tic Severity Score and Impairment Dimension Score).
次要结局
- Supplementary Motor Area (SMA) GABA concentration as measured by LCModel (Institutional Units)(Baseline to week 7)
- Functional connectivity of the Supplementary Motor Area (SMA) and the dominant Primary Motor Cortex (M1)(Baseline to week 7)
研究者
Frank MacMaster, PhD
Associate Professor
University of Calgary