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Transcranial Magnetic Stimulation for Children With Tourette's Syndrome

TICS: Transcranial Magnetic Stimulation for Children With Tourette's Syndrome

Status
Completed
Phases
NA
Study type
Interventional
Source
ClinicalTrials.gov
Registry ID
NCT02356003
Acronym
TICS
Enrollment
10
Registered
2015-02-04
Start date
2015-05-31
Completion date
2018-12-31
Last updated
2020-10-29

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Tourette Syndrome

Keywords

Tourette Syndrome, Children, Tics

Brief summary

Tics are the core symptom of Tourette syndrome. These are repetitive, sudden, semi-voluntary movements or sounds. In some children, these tics can be especially bad and require treatment, however, options are limited. It is only with time and practice that youth with Tourette syndrome are better able to suppress their tics. For these reasons, new interventions are needed. The investigators will target a brain region involved in tics called the supplementary motor area. Using low frequency repetitive transcranial magnetic stimulation, the investigators will inhibit the activity, in a similar way to the tic suppression that develops with age. The investigators propose the following objectives: (Aim 1) The investigators hypothesize that Tourette syndrome symptom severity (as measured by the Yale Global Tic severity Scale) will decrease with low frequency repetitive transcranial magnetic stimulation targeting the supplementary motor area. (Aim 2) The investigators further hypothesize that improvement in Tourette syndrome symptoms will be moderated by low frequency repetitive transcranial magnetic stimulation induced changes in GABA and glutamate in the supplementary motor area, and changes in the functional connectivity between the supplementary motor area and primary motor cortex. Eleven children (7-12 years of age) with Tourette syndrome will be undergo low frequency repetitive transcranial magnetic stimulation (five times a week for three weeks). After the three weeks, they will look for changes in tic severity and brain chemistry and function. By developing a novel avenue for treating Tourette syndrome, they can directly impact the care of children by reducing the severity of tics and improving quality of life.

Detailed description

Background Tourette syndrome is very common. It affects over 80,000 Canadian youth. Tics are the core symptom of Tourette syndrome. These are repetitive, sudden, semi-voluntary movements or sounds. In some children, these tics can be especially bad and require treatment, however, options are limited. Medications for Tourette syndrome carry significant risk of side effects. Behavioral treatments, like habit reversal therapy, show promise and are safe, but are difficult to apply to younger children. It is only with time and practice that youth with Tourette syndrome are better able to suppress their tics. Finally, neither medication nor behavior therapies directly target the root cause of the tics. For these reasons, new interventions are needed. Specific Objectives The investigators will target a key brain region involved in tics. It is called the supplementary motor area. Using low frequency repetitive transcranial magnetic stimulation, they will inhibit the activity of that brain region, in a similar way to the tic suppression that develops with age. The investigators propose the following specific objectives: (Aim 1) The investigators will characterize the effect of low frequency repetitive transcranial magnetic stimulation of the supplementary motor area on Tourette syndrome symptoms. They hypothesize that Tourette syndrome symptom severity (as measured by the Yale Global Tic severity Scale) will decrease with low frequency repetitive transcranial magnetic stimulation targeting the supplementary motor area. (Aim 2) The investigators will identify the changes in brain metabolites (glutamate and GABA) and functional connectivity caused by low frequency repetitive transcranial magnetic stimulation that normalize brain activity. They hypothesize that improvement in Tourette syndrome symptoms will be moderated by low frequency repetitive transcranial magnetic stimulation induced changes in GABA and glutamate in the supplementary motor area. This will be assessed with proton magnetic resonance spectroscopy, potentiation of GABAergic neurotransmission assessed with short-interval cortical inhibition, and changes in the functional connectivity between the supplementary motor area and primary motor cortex. Methods Eleven children (7-12 years of age) with Tourette syndrome will be undergo low frequency repetitive transcranial magnetic stimulation (5 times a week for three weeks). The investigators will assess the key variables with interviews and brain imaging of the children before and after the three-week intervention. After the three weeks, they will look for changes in tic severity and brain chemistry and function. Expected Results The investigators have pioneered transcranial magnetic stimulation applications in child and adolescent populations. By developing a novel avenue for treating Tourette syndrome, they can directly impact the care of children by reducing the severity of tics and improving quality of life.

Interventions

Baseline high-resolution anatomical magnetic resonance images will allow individualized neuronavigation (Brainsight 2, Rogue Research, Montreal QC) to co-register the transcranial magnetic stimulation Airfilm coil (Magistim, UK) precisely to the supplementary motor area as defined by functional magnetic resonance imaging. Interventional low frequency repetitive transcranial magnetic stimulation parameters will be: intensity 100% resting motor threshold, frequency 1 Hz, duration = 20 minutes (1200 stimulations). Treatments will occur on each weekday at the same time of day for three weeks (15 total). These are standard parameters for low frequency repetitive transcranial magnetic stimulation and are well tolerated in children.

Sponsors

University of Calgary
Lead SponsorOTHER

Study design

Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE

Eligibility

Sex/Gender
MALE
Age
7 Years to 12 Years
Healthy volunteers
No

Inclusion criteria

* Males * Right-handed

Exclusion criteria

* Female * Left-handed * Comorbid Attention Deficit Hyperactivity Disorder

Design outcomes

Primary

MeasureTime frameDescription
Yale Global Tic Severity ScaleFour weeksMeasure of tic severity using the Yale Global Tic Severity Scale (YGTSS). This is the standard measure for studies of Tourette's syndrome. The Global Severity Score has a range of 0- 100. A higher score on all scales suggests greater severity of tics.

Secondary

MeasureTime frameDescription
Glutamate ConcentrationFour weeksGlutamate concentration in the supplementary motor area
Functional ConnectivityFour weeksFunctional connectivity between the supplementary motor area and primary motor cortex as measured with resting state functional magnetic resonance imaging (rs-fMRI). T-value is the fMRI statistic that shows the level of connectivity. The higher the T-value, the greater the level of connectivity.

Countries

Canada

Participant flow

Participants by arm

ArmCount
Low Frequency rTMS
Eleven children (7-12 years of age) with Tourette syndrome will be undergo low frequency repetitive transcranial magnetic stimulation (5 times a week for three weeks). Low frequency repetitive transcranial magnetic stimulation: Baseline high-resolution anatomical magnetic resonance images will allow individualized neuronavigation (Brainsight 2, Rogue Research, Montreal QC) to co-register the transcranial magnetic stimulation Airfilm coil (Magistim, UK) precisely to the supplementary motor area as defined by functional magnetic resonance imaging. Interventional low frequency repetitive transcranial magnetic stimulation parameters will be: intensity 100% resting motor threshold, frequency 1 Hz, duration = 20 minutes (1200 stimulations). Treatments will occur on each weekday at the same time of day for three weeks (15 total). These are standard parameters for low frequency repetitive transcranial magnetic stimulation and are well tolerated in children.
10
Total10

Baseline characteristics

CharacteristicLow Frequency rTMS
Age, Categorical
<=18 years
10 Participants
Age, Categorical
>=65 years
0 Participants
Age, Categorical
Between 18 and 65 years
0 Participants
Age, Continuous11.524 years
STANDARD_DEVIATION 1.995
Ethnicity (NIH/OMB)
Hispanic or Latino
0 Participants
Ethnicity (NIH/OMB)
Not Hispanic or Latino
10 Participants
Ethnicity (NIH/OMB)
Unknown or Not Reported
0 Participants
Race (NIH/OMB)
American Indian or Alaska Native
0 Participants
Race (NIH/OMB)
Asian
0 Participants
Race (NIH/OMB)
Black or African American
0 Participants
Race (NIH/OMB)
More than one race
0 Participants
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
0 Participants
Race (NIH/OMB)
Unknown or Not Reported
0 Participants
Race (NIH/OMB)
White
10 Participants
Region of Enrollment
Canada
10 participants
Sex: Female, Male
Female
2 Participants
Sex: Female, Male
Male
8 Participants
Yale Global Tic Severity Scale (YGTSS)64.40 units on a scale
STANDARD_DEVIATION 19.83

Adverse events

Event typeEG000
affected / at risk
deaths
Total, all-cause mortality
0 / 10
other
Total, other adverse events
0 / 10
serious
Total, serious adverse events
0 / 10

Outcome results

Primary

Yale Global Tic Severity Scale

Measure of tic severity using the Yale Global Tic Severity Scale (YGTSS). This is the standard measure for studies of Tourette's syndrome. The Global Severity Score has a range of 0- 100. A higher score on all scales suggests greater severity of tics.

Time frame: Four weeks

Population: We stopped recruitment at 10 as the study ran out of money.

ArmMeasureGroupValue (MEAN)Dispersion
Low Frequency rTMSYale Global Tic Severity ScaleBaseline64.40 units on a scaleStandard Deviation 19.83
Low Frequency rTMSYale Global Tic Severity ScalePost-rTMS26.40 units on a scaleStandard Deviation 14.86
Secondary

Functional Connectivity

Functional connectivity between the supplementary motor area and primary motor cortex as measured with resting state functional magnetic resonance imaging (rs-fMRI). T-value is the fMRI statistic that shows the level of connectivity. The higher the T-value, the greater the level of connectivity.

Time frame: Four weeks

ArmMeasureValue (NUMBER)
Low Frequency rTMSFunctional Connectivity1.89 T-value
Secondary

Glutamate Concentration

Glutamate concentration in the supplementary motor area

Time frame: Four weeks

Population: We stopped recruitment at 10 as the study ran out of money.

ArmMeasureGroupValue (MEAN)Dispersion
Low Frequency rTMSGlutamate ConcentrationBaseline14.2 mMStandard Deviation 1.73
Low Frequency rTMSGlutamate ConcentrationPost-rTMS13.4 mMStandard Deviation 1.38

Source: ClinicalTrials.gov · Data processed: Feb 20, 2026