Theta Burst Stimulation to Improve Inhibitory Motor Physiology in Tourette Syndrome

Decades of Tourette Syndrome (TS) neuroimaging research has revealed abnormal cortical and subcortical motor system network, hypothesized to result from maladaptive plasticity. Repetitive transcranial magnetic stimulation ([r]TMS) is a promising technology that utilizes the concept of neuroplasticity to modulate brain circuits. TMS modulation has the distinct advantage in terms of its non-invasive nature. Furthermore, unique stimulation paradigms such as intermittent theta-burst repetitive TMS (iTBS) allows for short stimulation time (<3 min).

Using a sham-controlled protocol, the investigators propose modulating pre-SMA output using iTBS, based on our prior data of abnormal pre-SMA-mediated motor system regulation. hypothesize pre-SMA modulation results in increased pre-SMA-mediated motor inhibition. Enhancing these inhibitory measures with pre-SMA-iTBS provides the basis for improving inhibitory function in TS patients, leading to our long-term goal of neuro-stimulation to achieve clinical tic reduction.

Study Overview

• Status: Recruiting
• Conditions: Tourette Syndrome; Tourette Syndrome in Children; Tourette Syndrome in Adolescence; Tourette Syndrome, Modifier of
• Intervention / Treatment: Device: iTBS

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Early Phase 1

Contacts and Locations

• Study Contact: Name: Molly Griffith; Phone Number: 513-636-9669; Email: molly.griffith@cchmc.org

Study Locations

• United States
  • Ohio
    • Cincinnati, Ohio, United States, 45229
      • Recruiting
      • Cincinnati Children's Hospital Medical Center
      • Contact: Karlee Migneault; Phone Number: 513-803-5299; Email: karlee.migneault@cchmc.org
      • Principal Investigator: Travis R Larsh, MD
      • Sub-Investigator: Steve W Wu, MD
      • Sub-Investigator: Ernest V Pedapati, MD MS
      • Sub-Investigator: Donald L Gilbert, MD MS
      • Sub-Investigator: Paul S Horn, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 10 years to 21 years (Child, Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

Participants of any sex, race, or ethnicity meeting all criteria listed below will be included in the study:

1. Aged 10-21 years
2. Fluent in English
3. DSM-5 diagnosis of TS, confirmed by the clinical team
4. Able to participate in the informed consent process, provide voluntary informed consent/assent and provide a spontaneous narrative description of the key elements of the study.
5. Clinical stability: determined by a physician, no switch of psychotropic medications or increase in dosage in the last 14 days from TMS treatment start; no change in other therapeutic interventions in last 14 days from TMS treatment start.

Exclusion Criteria:

1. Any neurodevelopmental, psychiatric condition other than TS, ADHD, or OCD, or mild anxiety based on review of K-SADS. Note - if an exclusionary psychiatric diagnosis is suspected based on K-SADS, the research physician will follow up with the parent and referral will be made to psychology or psychiatry as appropriate.
2. Presence of metallic foreign bodies or implanted medical devices.
3. Not meeting inclusion criteria as described above
4. Non-fluency in English, as English is the language in the validated clinical questionnaires, and the participant must be able to understand real-time instructions from the study staff

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Single Group Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: iTBS; Each participant will have two separate study days in the TMS lab. On one day, the participant will receive active pre-SMA iTBS. On the other day, the patricipant will receive sham pre-SMA iTBS. The order that active versus sham is given will be randomized and the participant will be blinded. After each iTBS session, blinding assessment will be performed. To avoid contamination of results, a minimum of 5 days between study days will be required.	Device: iTBS; intermittent theta burst stimulation with TMS
Sham Comparator: Sham iTBS; Each participant will have two separate study days in the TMS lab. On one day, the participant will receive active pre-SMA iTBS. On the other day, the patricipant will receive sham pre-SMA iTBS. The order that active versus sham is given will be randomized and the participant will be blinded. After each iTBS session, blinding assessment will be performed. To avoid contamination of results, a minimum of 5 days between study days will be required.	Device: iTBS; intermittent theta burst stimulation with TMS

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
change in cortical silent period (cSP)	cSP is a biomarker of inhibitory motor physiology	On the same day, we will assess change in cSP prior to active (or sham) iTBS treatment and immediately after iTBS treatment

Collaborators and Investigators

• Sponsor: Children's Hospital Medical Center, Cincinnati
• Collaborators: Tourette Association of America

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2022
• Primary Completion (Estimated): December 31, 2024
• Study Completion (Estimated): February 17, 2025

Study Registration Dates

• First Submitted: November 8, 2022
• First Submitted That Met QC Criteria: November 23, 2022
• First Posted (Actual): November 29, 2022

Study Record Updates

• Last Update Posted (Estimated): February 6, 2024
• Last Update Submitted That Met QC Criteria: February 5, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Pathologic Processes; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Disease; Genetic Diseases, Inborn; Basal Ganglia Diseases; Movement Disorders; Neurodegenerative Diseases; Heredodegenerative Disorders, Nervous System; Neurodevelopmental Disorders; Tic Disorders; Syndrome; Tourette Syndrome
• Other Study ID Numbers: 2022-0747

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes