Tic DisordersTICS-CIHRNCT03844919
TICS: Transcranial Magnetic Stimulation for Intervening in Children With Tourette's Syndrome (CIHR)
A study testing rTMS + CBIT in people with Tic Disorders, run by University of Calgary at 1 site in Canada.
Trial 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. Read more about this study
- Who is it for?
- Ages 6 to 18 years
- Conditions the study is for
- Tic Disorders
- What is being tested?
- rTMS + CBIT
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 50 participants
- Where
- 1 siteCanada
- Study dates
- 1 Sep 2019to 1 Nov 2022
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 6 to 18 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Diagnosis of Tourette's syndrome
- IQ greater than 80
- English fluency (to enable assent and consent).
Who cannot join
- Diagnosis of mania or schizophrenia
- Impediments to TMS or MRI.
Trial locations and contacts
1 site in 1 country.
Canada1 site, 1 recruiting
- Recruiting
Alberta Children's Hospital
Calgary, Alberta, T3B 6A8
Frank P MacMaster, PhD, 403-955-2784, fmacmast@ucalgary.ca
About this study
Official title: TICS: Transcranial Magnetic Stimulation for Intervening in Children With Tourette's Syndrome
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:
Read more
(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).
Read the 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).
- Conditions
- Tic Disorders
- Being tested
- rTMS + CBIT, Sham rTMS + CBIT
- Keywords
- Children, Adolescent, CBIT, Transcranial magnetic stimulation, Comprehensive Behavioral Intervention for Tics, rTMS, TMS, MRI, Tourette's Syndrome
- Medical subject headings
- Tic Disorders, Tourette Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
rTMS + CBITDevice
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.
Sham rTMS + CBITBehavioural
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.
| Study group | Role | What they receive |
|---|---|---|
| rTMS + CBIT | Experimental | Repetitive transcranial magnetic stimulation (rTMS) and Comprehensive Behavioural Intervention for Tics (CBIT) Receives: Device: rTMS + CBIT; Behavioral: Sham rTMS + CBIT |
| Sham rTMS + CBIT | Active comparator | Sham repetitive transcranial magnetic stimulation (rTMS) and Comprehensive Behavioural Intervention for Tics (CBIT) Receives: Behavioral: Sham rTMS + CBIT |
What is being measured
The primary outcome is the main question the study is designed to answer.
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:
- Total Motor (0 to 25)
- 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).
Measured: Baseline to week 7
Secondary outcomes (2)
Supplementary Motor Area (SMA) GABA concentration as measured by LCModel (Institutional Units)
10% increase in GABA concentration in the Supplementary Motor Area (SMA) as measured by LCModel (Institutional Units)
Measured: Baseline to week 7
Functional connectivity of the Supplementary Motor Area (SMA) and the dominant Primary Motor Cortex (M1)
Functional connectivity, as measured using SPM12, of the Supplementary Motor Area (SMA) and the dominant Primary Motor Cortex (M1).
Measured: Baseline to week 7
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Feb 2019
- Study start1 Sep 2019
- Primary completion1 May 2022 (estimated)
- Study completion1 Nov 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Tic DisordersStudies of the same condition, open and under way.
- More trials run by University of CalgaryThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- 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.
- Masking
- Double blind
- Who is masked
- Participant, Outcomes assessor
- Enrolment
- 50 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Calgary
- Sponsor type
- University, hospital or other
- Collaborators
- Canadian Institutes of Health Research (CIHR)
- Responsible party
- Principal investigator, Frank MacMaster, PhD, University of Calgary
- Investigators
- Frank P MacMaster, PhD, Principal investigator, University of Calgary
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03844919
- Sponsor's protocol ID
- REB18-0220
- Acronym
- TICS-CIHR
- Status last verified
- Nov 2021
- First submitted
- 11 Feb 2019
- Last updated
- 10 Nov 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Only de-identified data would be shared.
Publications
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.
PubMed 34952879
Study at a glance
From the registry record, last updated by the sponsor on 10 Nov 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- TICS: Transcranial Magnetic Stimulation for Intervening in Children With Tourette's Syndrome
- ClinicalTrials.gov ID
- NCT03844919
- Acronym / sponsor ID
- TICS-CIHR / REB18-0220
- Conditions
- Tic Disorders
- Keywords
- Children, Adolescent, CBIT, Transcranial magnetic stimulation, Comprehensive Behavioral Intervention for Tics, rTMS, TMS, MRI
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 50 participants (estimated)
- Lead sponsor
- University of CalgaryUniversity, hospital or other
- Collaborators
- Canadian Institutes of Health Research (CIHR)
- Study start
- 1 Sep 2019 (actual)
- Primary completion
- 1 May 2022 (estimated)
- Study completion
- 1 Nov 2022 (estimated)
- First posted
- 19 Feb 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, outcomes assessor)
- Number of arms
- 2
- 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.
| Arm | Type | Receives |
|---|---|---|
| rTMS + CBIT | Experimental | Device: rTMS + CBIT, Behavioral: Sham rTMS + CBITRepetitive transcranial magnetic stimulation (rTMS) and Comprehensive Behavioural Intervention for Tics (CBIT) |
| Sham rTMS + CBIT | Active comparator | Behavioral: Sham rTMS + CBITSham repetitive transcranial magnetic stimulation (rTMS) and Comprehensive Behavioural Intervention for Tics (CBIT) |
Who may qualify
- Ages
- 6 to 18 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (3 listed)
- Diagnosis of Tourette's syndrome
- IQ greater than 80
- English fluency (to enable assent and consent).
Key exclusion criteria (2 listed)
- Diagnosis of mania or schizophrenia
- Impediments to TMS or MRI.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| rTMS + CBITRepetitive 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. | Device | rTMS + CBIT |
| Sham rTMS + CBITSham 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. | Behavioural | Sham rTMS + CBIT, rTMS + CBIT |
Primary outcome
Yale Global Tic Severity Scale Total Tic score (YGTSS)
Time frame: 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).
2 secondary outcomes
Supplementary Motor Area (SMA) GABA concentration as measured by LCModel (Institutional Units)
Time frame: Baseline to week 7
Functional connectivity of the Supplementary Motor Area (SMA) and the dominant Primary Motor Cortex (M1)
Time frame: Baseline to week 7
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Nov 2021.
- Derived from this study: PubMed 34952879Kahl 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.
- Individual participant dataSharing planned: Yes. Only de-identified data would be shared.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Frank P MacMaster, PhD principal investigator
University of Calgary
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing rTMS + CBIT in people with Tic Disorders, run by University of Calgary at 1 site in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 10 Nov 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Frank MacMaster, PhD (4039552784, fmacmast@ucalgary.ca), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Yale Global Tic Severity Scale Total Tic score (YGTSS) (time frame: Baseline to week 7). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03844919, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Nov 2021.