Tic Disorders, Tics, Tic, Motor, Tic Disorder, Childhood, Tourette Syndrome, Tourette Syndrome in Children, Tourette Syndrome in Adolescence
Conditions
Brief summary
The study will examine whether combining Comprehensive Behavioral Intervention for Tics (CBIT) with inhibition of the supplementary motor area (SMA) using transcranial magnetic stimulation (TMS) normalizes activity in the SMA-connected circuits, improves tic suppression ability, and enhances CBIT outcomes in young people with tic disorder. The study will also examine different TMS dosing strategies.
Detailed description
All participants will receive 10 daily sessions of CBIT, a well-established behavioral treatment that is considered by the American Academy of Neurology to be the first-line intervention for tics. Immediately prior to each CBIT session, participants will undergo TMS targeting the SMA. The specific type of TMS procedure will be randomly assigned between subjects and be either: 1 Hz repetitive TMS (rTMS), continuous theta burst stimulation (cTBS), or sham stimulation.
Interventions
CBIT is a manualized treatment program focused on tic management skills
DEVICERepetitive Transcranial Magnetic Stimulation (rTMS)
During repetitive transcranial magnetic stimulation (rTMS), a electromagnetic coil is placed against the scalp while an electromagnet painlessly delivers a magnetic pulse that stimulates nerve cells in the target brain region
During continuous theta burst stimulation (cTBS), a electromagnetic coil is placed against the while an electromagnet painlessly delivers magnetic bursts that stimulate nerve cells in the target brain region
Sponsors
University of Minnesota
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
12 Years to 21 Years
Healthy volunteers
No
Inclusion criteria
* Current chronic motor and/or vocal tics, defined as tics for at least 1 year without a tic-free period of more than 3 consecutive months. Tics must not be due to a medical condition or the direct physiological effects of a substance. * At least moderate tic severity, defined as a Yale Global Tic Severity Scale total score ≥14 (≥9 for those with motor or vocal tics only). * Full scale IQ greater than or equal to 70 * English fluency to ensure comprehension of study measures and instructions. * Right-handed
Exclusion criteria
* Medical conditions contraindicated or associated with altered TMS risk profile, including history of intracranial pathology, epilepsy or seizure disorders, traumatic brain injury, brain tumor, stroke, implanted medical devices or metallic objects in the head, current pregnancy or participants of childbearing age not using effective contraception, or any other medical condition deemed serious or contraindicated by a study physician * Inability to undergo MRI. * Left handedness. * Active suicidality. * Previous diagnosis of psychosis or cognitive disability. * Substance abuse or dependence within the past year. * Concurrent psychotherapy focused on tics. * Neuroleptic/antipsychotic medications. * Taking a medication that has not reached stability criterion (same medication and dose for 6 weeks with no planned changes over the intervention period)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Resting State fMRI Connectivity of SMA-mediated Brain Circuits | baseline to post-treatment; approximately 10 days | For each participant, signal intensity (unitless measure) will be measured using fMRI in the supplementary motor area (SMA) during a finger tapping task. An ANOVA will be conducted to compare change in signal intensity within SMA from pre- to post-treatment across the groups. The outcome will be reported as an effect size value (Cohen's d). |
| Change in SMA Activation | baseline to post-treatment; approximately 10 days | For each participant, signal intensity (unitless measure) will be measured using fMRI in the supplementary motor area (SMA) during a finger tapping task. An ANOVA will be conducted to compare change in signal intensity within SMA from pre- to post-treatment across the groups. The outcome will be reported as an effect size value (Cohen's d). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Safety: Measured as Rate of Adverse Events Related to Study Treatment | approximately 3-4 months | The number of adverse events judged to be treatment related will be totaled and reported for each group. |
| Change in Tic Suppression Task | baseline to 3 months post-treatment | The Tic Suppression Task is a clinician-rated tool for assessing tic frequency. A video recording of participant is rated and yields a score in units of tics per minute. Outcome reported as change from baseline to post treatment; change from baseline to 1 month post treatment; change from baseline to 3 months post treatment; change from post treatment to 1 month post treatment; and change from post treatment to 3 months post treatment. |
| Feasibility: Measured as Participant Treatment Completion | approximately 3-4 months | For each group, the number of participants who completed at least 80% of treatment sessions will be totaled and reported for each group. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Active Comparator: 1 Hz rTMS Participants in this arm will receive Comprehensive Behavioral Intervention for Tics (CBIT) with 1 Hz repetitive Transcranial Magnetic Stimulation (rTMS). | 17 |
| Active Comparator: cTBS Participants in this arm will receive Comprehensive Behavioral Intervention for Tics (CBIT) with continuous Theta Burst Stimulation (cTBS). | 16 |
| Sham Comparator: Sham Participants in this arm will receive Comprehensive Behavioral Intervention for Tics (CBIT) with sham stimulation. | 17 |
| Total | 50 |
Baseline characteristics
| Characteristic | Active Comparator: 1 Hz rTMS | Active Comparator: cTBS | Sham Comparator: Sham | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 13 Participants | 12 Participants | 12 Participants | 37 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 4 Participants | 4 Participants | 5 Participants | 13 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 2 Participants | 2 Participants | 2 Participants | 6 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) White | 13 Participants | 14 Participants | 15 Participants | 42 Participants |
| Sex: Female, Male Female | 8 Participants | 8 Participants | 7 Participants | 23 Participants |
| Sex: Female, Male Male | 9 Participants | 8 Participants | 10 Participants | 27 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 17 | 0 / 15 | 0 / 16 |
| other Total, other adverse events | 17 / 17 | 15 / 15 | 14 / 16 |
| serious Total, serious adverse events | 0 / 17 | 0 / 15 | 0 / 16 |
Outcome results
Primary
Change in Resting State fMRI Connectivity of SMA-mediated Brain Circuits
For each participant, signal intensity (unitless measure) will be measured using fMRI in the supplementary motor area (SMA) during a finger tapping task. An ANOVA will be conducted to compare change in signal intensity within SMA from pre- to post-treatment across the groups. The outcome will be reported as an effect size value (Cohen's d).
Time frame: baseline to post-treatment; approximately 10 days
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CBIT + rTMS | Change in Resting State fMRI Connectivity of SMA-mediated Brain Circuits | 0.0312 eta squared | Standard Deviation 0.05 |
| CBIT + cTBS | Change in Resting State fMRI Connectivity of SMA-mediated Brain Circuits | 0.261 eta squared | Standard Deviation 0.05 |
| CBIT + Sham | Change in Resting State fMRI Connectivity of SMA-mediated Brain Circuits | 0.158 eta squared | Standard Deviation 0.03 |
Primary
Change in SMA Activation
For each participant, signal intensity (unitless measure) will be measured using fMRI in the supplementary motor area (SMA) during a finger tapping task. An ANOVA will be conducted to compare change in signal intensity within SMA from pre- to post-treatment across the groups. The outcome will be reported as an effect size value (Cohen's d).
Time frame: baseline to post-treatment; approximately 10 days
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CBIT + rTMS | Change in SMA Activation | 0.45 eta squared | Standard Deviation 1.25 |
| CBIT + cTBS | Change in SMA Activation | 0.01 eta squared | Standard Deviation 1.25 |
| CBIT + Sham | Change in SMA Activation | 0.27 eta squared | Standard Deviation 1.3 |
Secondary
Change in Tic Suppression Task
The Tic Suppression Task is a clinician-rated tool for assessing tic frequency. A video recording of participant is rated and yields a score in units of tics per minute. Outcome reported as change from baseline to post treatment; change from baseline to 1 month post treatment; change from baseline to 3 months post treatment; change from post treatment to 1 month post treatment; and change from post treatment to 3 months post treatment.
Time frame: baseline to 3 months post-treatment
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CBIT + rTMS | Change in Tic Suppression Task | 0.58 tics per minute | Standard Deviation 9.47 |
| CBIT + cTBS | Change in Tic Suppression Task | -3.83 tics per minute | Standard Deviation 23.92 |
| CBIT + Sham | Change in Tic Suppression Task | -8.24 tics per minute | Standard Deviation 15.71 |
Secondary
Feasibility: Measured as Participant Treatment Completion
For each group, the number of participants who completed at least 80% of treatment sessions will be totaled and reported for each group.
Time frame: approximately 3-4 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| CBIT + rTMS | Feasibility: Measured as Participant Treatment Completion | 17 participants |
| CBIT + cTBS | Feasibility: Measured as Participant Treatment Completion | 15 participants |
| CBIT + Sham | Feasibility: Measured as Participant Treatment Completion | 16 participants |
Secondary
Safety: Measured as Rate of Adverse Events Related to Study Treatment
The number of adverse events judged to be treatment related will be totaled and reported for each group.
Time frame: approximately 3-4 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| CBIT + rTMS | Safety: Measured as Rate of Adverse Events Related to Study Treatment | 46 events |
| CBIT + cTBS | Safety: Measured as Rate of Adverse Events Related to Study Treatment | 22 events |
| CBIT + Sham | Safety: Measured as Rate of Adverse Events Related to Study Treatment | 18 events |