Combined CBIT and rTMS to Improve Tourette's Syndrome

NCT ID: NCT04795908

Last Updated: 2024-04-30

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 3 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-12-17
• Study Completion Date: 2023-01-18

Brief Summary

The investigator will apply 16 sessions of repetitive transcranial magnetic stimulation (rTMS) over 4 consecutive days for adult patients suffering from Tourette's Syndrome. Following rTMS, patients will undergo 8 sessions of Comprehensive Behavioral Intervention for Tics (CBIT) over 10 weeks via telemedicine. Clinical improvement in tic severity will be the primary outcome measure. Secondary outcome measures including underlying physiological effects will be measured via functional magnetic resonance imaginge (fMRI), high-density electroencephalograhy (HD-EEG), and TMS.

Detailed Description

Patients will be randomly assigned to active or sham stimulation, with 10 in each group, followed by 10 weeks of tele-CBIT. Patients will have primary and secondary outcome measures performed at four time points: Baseline (T0), following rTMS (T1), following CBIT (T2), and 1 month later (T3). The rTMS protocol will consist of 6 trains targeted to the supplementary motor area (SMA) lasting 5 minutes each (300 pulses per train) with an intertrain interval of 1 minute for a total duration of 35 minutes (1800 pulses). Patients will receive 4 sessions each day on 4 consecutive days for a total of 16 sessions. Daily duration of this study protocol should last approximately 170 minutes including a 10 minute break in between each session. The sham protocol will be the same except a sham coil will be used instead of an active coil. Following rTMS, patients will undergo 10 weeks of tele-CBIT.

The following outcome measures will be collected at four timepoints (T0, T1, T2, and T3):

Tics will be examined with the standardized Yale Global Tic Severity Scale (YGTSS) and the modified Rush Videotape Tic Rating Scale (mRVTRS), and co-morbid symptoms with the Beck Depression Inventory (BDI), Beck Anxiety Inventory (BAI), Yale-Brown Obsessive Compulsive Scale (Y-BOCS) and Adult ADHD Self-Reports Scale (ASRS). Quality of life will be assessed with the Gilles de la Tourette Syndrome - Quality of Life scale (GTS-QOL).

TMS measures: A single-pulse of TMS will be targeted over the motor cortex to generate a motor evoked potential (MEP), which can be captured on EMG. The rest of the EMG will be analyzed to assess the time between the TMS pulse and the MEP (also known as the latency) and the amount of time muscle activity remains silent following the MEP (also known as the cortical silent period). In a paired-pulse TMS paradigm, a subthreshold pulse will be provided followed by an interstimulus interval and then subsequent delivery of a suprathreshold pulse. When the interstimulus interval is short (1-4 msec), the ratio of MEP amplitudes produced by these two pulses is known as short interval intracortical inhibition (SICI).

fMRI measure: Functional MRI will be used to record Blood Oxygen Level Dependent (BOLD) activity changes in patients at rest.

HD-EEG measure: A 128-electrode cap will be used to assess electrical activity in patients at rest and actively trying to suppress their tics.

Conditions

Tourette Syndrome

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Active rTMS Group

Patients will be seated in a comfortable reclined chair. The neurostimulation protocol will include 1-Hz rTMS over the bilateral SMA at 110% resting motor threshold (RMT). The SMA will be identified as 4 cm anterior to the vertex (Cz in standard 10-20 EEG setup). Each session will consist of 6 trains lasting 5 minutes each (300 pulses per train) with an intertrain interval of 1 minute for a total duration of 35 minutes (1800 pulses). Patients will receive 4 sessions each day on 4 consecutive days for a total of 16 sessions. Daily duration of this study protocol should last approximately 170 minutes including a 10 minute break in between each session.

Group Type: EXPERIMENTAL

Transcranial Magnetic Stimulation

Intervention Type: DEVICE

rTMS will be delivered using a MagStim Super Rapid2 TMS therapy system.

Comprehensive behavioral intervention

Intervention Type: BEHAVIORAL

Patients will receive CBIT with a therapist trained in CBIT. Each session will last about an hour and will be delivered remotely via telemedicine. Sessions will be tailed to the patient's individual needs.

Interventions

Transcranial Magnetic Stimulation

rTMS will be delivered using a MagStim Super Rapid2 TMS therapy system.

Intervention Type: DEVICE

Comprehensive behavioral intervention

Patients will receive CBIT with a therapist trained in CBIT. Each session will last about an hour and will be delivered remotely via telemedicine. Sessions will be tailed to the patient's individual needs.

Intervention Type: BEHAVIORAL

Eligibility Criteria

Inclusion Criteria

• Any patient diagnosed with Tourette Syndrome > 18 years of age with moderate tic severity.
• Participants will be allowed to continue oral medications that they are taking for TS concurrently but will not be allowed to change their concurrent medication regimen throughout the duration of the study

Exclusion Criteria

• Presence of metallic objects or neurostimulators in the brain
• Pregnancy
• History of active seizures or epilepsy
• Contraindications to receiving fMRI, such as claustrophobia
• Inability to participate in CBIT due to other underlying cognitive or medical condition

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 85 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Florida

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Aparna Wagle Shukla, MD

Role: PRINCIPAL_INVESTIGATOR

University of Florida

Locations

Fixel Neurologic Institute

Gainesville, Florida, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

OCR40702

Identifier Type: OTHER

Identifier Source: secondary_id

IRB202002701-A

Identifier Type: -

Identifier Source: org_study_id