Clinical trial NCT03844919: TICS: Transcranial Magnetic Stimulation for Intervening in Children With Tourette's Syndrome (CIHR)
Official title: TICS: Transcranial Magnetic Stimulation for Intervening in Children With Tourette's Syndrome
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Tic Disorders
Keywords: Children
Adolescent
CBIT
Transcranial magnetic stimulation
Comprehensive Behavioral Intervention for Tics
rTMS
TMS
MRI
Tourette's Syndrome
Lead sponsor: University of Calgary
Sponsor class: OTHER
Collaborators: name: Canadian Institutes of Health Research (CIHR)
First posted: 2019-02-19
Enrollment: 50
Sex: ALL
Minimum age (years): 6
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Children (N = 50, 6-18 years) with TS will be randomized to either a (1) rTMS+CBIT arm, or a (2) sham rTMS+CBIT arm.
Primary purpose: TREATMENT

Brief summary: 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).

Detailed description: 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.

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).

Eligibility criteria: Inclusion Criteria:

1. Diagnosis of Tourette's syndrome
2. IQ greater than 80
3. English fluency (to enable assent and consent).

Exclusion Criteria:

1. Diagnosis of mania or schizophrenia
2. Impediments to TMS or MRI.

Primary outcomes:
measure: Yale Global Tic Severity Scale Total Tic score (YGTSS)
timeFrame: Baseline to week 7
Secondary outcomes:
measure: Supplementary Motor Area (SMA) GABA concentration as measured by LCModel (Institutional Units)
timeFrame: Baseline to week 7
measure: Functional connectivity of the Supplementary Motor Area (SMA) and the dominant Primary Motor Cortex (M1)
timeFrame: Baseline to week 7
Other outcomes:
measure: Yale Global Tic Severity Scale Total Tic score (YGTSS) post CBIT
timeFrame: Baseline to week 11
Locations:
city: Calgary
country: Canada
facility: Alberta Children's Hospital
state: Alberta
Study officials:
affiliation: University of Calgary
name: Frank P MacMaster, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Kahl CK, Swansburg R, Kirton A, Pringsheim T, Wilcox G, Zewdie E, Harris A, Croarkin PE, Nettel-Aguirre A, Chenji S, MacMaster FP. Targeted Interventions in Tourette's using Advanced Neuroimaging and Stimulation (TITANS): study protocol for a double-blind, randomised controlled trial of transcranial magnetic stimulation (TMS) to the supplementary motor area in children with Tourette's syndrome. BMJ Open. 2021 Dec 24;11(12):e053156. doi: 10.1136/bmjopen-2021-053156.