NCT03844919

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).

Trial Health

43
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
50

participants targeted

Target at P25-P50 for not_applicable

Timeline
Completed

Started Sep 2019

Longer than P75 for not_applicable

Geographic Reach
1 country

1 active site

Status
unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

February 11, 2019

Completed
8 days until next milestone

First Posted

Study publicly available on registry

February 19, 2019

Completed
6 months until next milestone

Study Start

First participant enrolled

September 1, 2019

Completed
2.7 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

May 1, 2022

Completed
6 months until next milestone

Study Completion

Last participant's last visit for all outcomes

November 1, 2022

Completed
Last Updated

November 10, 2021

Status Verified

November 1, 2021

Enrollment Period

2.7 years

First QC Date

February 11, 2019

Last Update Submit

November 2, 2021

Conditions

Keywords

ChildrenAdolescentCBITTranscranial magnetic stimulationComprehensive Behavioral Intervention for TicsrTMSTMSMRITourette's Syndrome

Outcome Measures

Primary Outcomes (1)

  • Yale Global Tic Severity Scale Total Tic score (YGTSS)

    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).

    Baseline to week 7

Secondary Outcomes (2)

  • 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

Other Outcomes (1)

  • Yale Global Tic Severity Scale Total Tic score (YGTSS) post CBIT

    Baseline to week 11

Study Arms (2)

rTMS + CBIT

EXPERIMENTAL

Repetitive transcranial magnetic stimulation (rTMS) and Comprehensive Behavioural Intervention for Tics (CBIT)

Device: rTMS + CBITBehavioral: Sham rTMS + CBIT

Sham rTMS + CBIT

ACTIVE COMPARATOR

Sham repetitive transcranial magnetic stimulation (rTMS) and Comprehensive Behavioural Intervention for Tics (CBIT)

Behavioral: Sham rTMS + CBIT

Interventions

Repetitive Transcranial Magnetic Stimulation (rTMS) parameters are: intensity 100% resting motor threshold (RMT), frequency 1Hz, duration = 30 minutes (1800 stimulations; 900 per side), target - the supplementary motor area (SMA). Treatments occur on weekdays (T - F) for four weeks (20 total). The Comprehensive Behavioral Intervention for Tics (CBIT) will be completed over eight sessions that will average 60 minutes in duration. First, participants will undergo awareness training. Participants will then be introduced to competing response training, which involves performing a voluntary behaviour designed to disrupt the execution of the tic. The eight sessions will occur on Mondays, once a week for six weeks and then on weeks 8 and 10.

rTMS + CBIT

Sham rTMS (sham coil) will be paired with CBIT. Sham rTMS will be delivered over the same time-frame as above. CBIT will be identical to the above.

Sham rTMS + CBITrTMS + CBIT

Eligibility Criteria

Age6 Years - 18 Years
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17), Adult (18-64)

You may qualify if:

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

You may not qualify if:

  • Diagnosis of mania or schizophrenia
  • Impediments to TMS or MRI.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Alberta Children's Hospital

Calgary, Alberta, T3B 6A8, Canada

RECRUITING

Related Publications (1)

  • 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.

MeSH Terms

Conditions

Tic DisordersTourette Syndrome

Interventions

Transcranial Magnetic Stimulation

Condition Hierarchy (Ancestors)

Movement DisordersCentral Nervous System DiseasesNervous System DiseasesNeurodevelopmental DisordersMental DisordersBasal Ganglia DiseasesBrain DiseasesHeredodegenerative Disorders, Nervous SystemNeurodegenerative DiseasesGenetic Diseases, InbornCongenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Magnetic Field TherapyTherapeutics

Study Officials

  • Frank P MacMaster, PhD

    University of Calgary

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Frank MacMaster, PhD

CONTACT

Rose M Swansburg, MBT

CONTACT

Study Design

Study Type
interventional
Phase
not applicable
Allocation
RANDOMIZED
Masking
DOUBLE
Who Masked
PARTICIPANT, OUTCOMES ASSESSOR
Masking Details
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.
Purpose
TREATMENT
Intervention Model
PARALLEL
Model Details: 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.
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Associate Professor

Study Record Dates

First Submitted

February 11, 2019

First Posted

February 19, 2019

Study Start

September 1, 2019

Primary Completion

May 1, 2022

Study Completion

November 1, 2022

Last Updated

November 10, 2021

Record last verified: 2021-11

Data Sharing

IPD Sharing
Will share

Only de-identified data would be shared.

Shared Documents
STUDY PROTOCOL, SAP, ICF
Time Frame
Study protocol, SAP, and ICF is open to be shared now. De-identified data will be shared after we submitted our main papers. This is estimated in 2025.
Access Criteria
Email for permission from PI of project.

Locations