Teen and Adult Tic TMS Study

NCT07839377 | Recruiting FDA Device

• 1 other identifier: 25-43729
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

This project investigates safety, tolerability, and efficacy signals of accelerated continuous theta burst stimulation (cTBS), a form of inhibitory repetitive transcranial magnetic stimulation (rTMS), for patients with Tourette Syndrome and chronic tic disorders (CTD). It integrates resting-state functional MRI (fMRI) to assess changes in brain circuits and neurophysiology. CTD are neurodevelopmental disorders marked by motor and/or vocal tics, associated with dysfunction in cortico-striato-thalamo-cortical (CSTC) networks, particularly the supplementary motor area (SMA), primary motor cortex (M1), and connected regions. While low-frequency rTMS has shown preliminary benefits in pediatric populations, circuit-targeted approaches remain relatively unexplored in children, adolescents and adults, leaving no consensus about optimal applications. Participants will be randomized to receive 50 sessions of 1800 pulses of cTBS rTMS over two weeks, with five sessions/day targeting the SMA or M1. Assessments will include the Yale Global Tic Severity Scale (YGTSS) and MRI. Aim 1 Determine if cTBS to the M1 can reduce CTD symptoms and normalize abnormal network connectivity within the Somato-Cognitive Action Network (SCAN). Aim 2 Determine if cTBS to the SMA can reduce symptoms of CTD and normalize abnormal network connectivity within the Action Mode Network (AMN).

Conditions

Tic Disorder

Keywords

Tic; Tics; Tourette's; Tourette; Tourettes; Tic Disorder

Outcome Measures

Primary Outcomes (1)

• To assess the safety and tolerability of repeated theta burst TMS administration in adolescents age 15 - 35 years with CTD.

  This study's primary aim is to determine the safety and tolerability of repeated TMS administration in adolescents and adults ages 15 - 35 years with DSM-5 confirmed CTD of moderate or greater severity. These will be determined by protocol completion rate from enrollment to final visit, and tabulation of the individual and summed frequencies of reported and identified adverse events observed from study enrollment to final visit.

  All protocol visits (treatment days 1 - 10)

Secondary Outcomes (1)

• To examine the possible efficacy of repeated TMS administration on CTD symptom severity at two different brain regions (M1 and SMA).

  Screening, baseline, treatment day 5, treatment day 10, 1-week follow-up, 1-month follow-up

Other Outcomes (3)

• Change in Clinical Global Impression-Severity Scale (CGI-S) pre- vs post-TMS

  Baseline, treatment day 5, treatment day 10, 1-week follow-up, 1-month follow-up

• Change in Clinical Global Impression-Improvement Scale (CGI-I) pre- vs post-TMS

  Baseline, treatment day 5, treatment day 10, 1-week follow-up, 1-month follow-up

• Change in functional connectivity pre- vs post-TMS

  From time of enrollment to one week follow up after end of treatment (Week 4)

Study Arms (2)

M1 (primary motor cortex)

EXPERIMENTAL

Determine if cTBS to the M1 can reduce CTD symptoms and normalize abnormal network connectivity within the Somato-Cognitive Action Network (SCAN).

Device: cTBS (accelerated continuous theta burst stimulation)

SMA (supplementary motor area)

EXPERIMENTAL

Determine if cTBS to the SMA can reduce symptoms of CTD and normalize abnormal network connectivity within the Action Mode Network (AMN).

Device: cTBS (accelerated continuous theta burst stimulation)

Interventions

cTBS (accelerated continuous theta burst stimulation) DEVICE

Participants will be randomized to receive 50 sessions of 1800 pulses of cTBS rTMS over two weeks, with five sessions/day targeting the SMA or M1.

M1 (primary motor cortex); SMA (supplementary motor area)

Eligibility Criteria

• Age: 15 Years - 35 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Outpatients
• Ages 15 - 35 years old
• Meets DSM-5 criteria for persistent (chronic) vocal/motor tic disorder or Tourette's syndrome with screening YGTSS score ≥ 20 (moderate or greater severity).
• Moderate severity or intolerable side effects with at least one prior trial of an evidence-based anti-tic medication.
• Stable on chronic psychotropic medications and/or therapy for 6 weeks prior to the study and agreeable to continue current treatments without change throughout the study.
• Participants may continue to take medications and record daily usage throughout the study.
• Capacity to provide informed assent or consent and parent or legal guardian able to provide consent for minors.
• Ability to tolerate clinical study procedures.
• Successfully complete the screening forms without any contraindications.

You may not qualify if:

• Psychiatric: history of schizophrenia, bipolar disorder, substance /alcohol abuse disorder, current elevated suicide risk, prior psychosurgery.
• Neurologic: severe neurocognitive disorder, seizure disorder, certain structural brain lesions (e.g., intracranial mass lesions, TBI, hydrocephalus, sequelae of meningitis, frank brain injury).
• TMS contraindications: implanted device; presence of metal in the head, including eyes and ears (excluding dental implants); certain tics.
• Subjects with an unstable physical, systemic, or metabolic disorder (e.g., unstable hypertension; malnutrition).
• Females who are pregnant or nursing (as determined by a questionnaire and urine pregnancy test).
• Inability to complete the research protocol as determined by the Principal Investigator.

Sponsors & Collaborators

• University of California, San Francisco: lead

Study Sites (1)

University of California, San Francisco

San Francisco, California, 94107, United States

RECRUITING

Related Publications (32)

• Claudio-Campos K, Stevens D, Koo SW, Valko A, Bienvenu OJ, Budman CB, Cath DC, Darrow S, Geller D, Goes FS, Grados MA, Greenberg BD, Greenberg E, Hirschtritt ME, Illmann C, Ivankovic F, King RA, Knowles JA, Krasnow J, Lee PC, Lyon GJ, McCracken JT, Robertson MM, Osiecki L, Riddle MA, Rouleau G, Sandor P, Nestadt G, Samuels J, Scharf JM, Mathews CA; Tourette Association of America International Consortium for Genetics (TAAICG) and the OCD Collaborative Genetics Association Study (OCGAS). Is Persistent Motor or Vocal Tic Disorder a Milder Form of Tourette Syndrome? Mov Disord. 2021 Aug;36(8):1899-1910. doi: 10.1002/mds.28593. Epub 2021 May 4.

  PMID: 33942911 BACKGROUND

• Roessner V, Eichele H, Stern JS, Skov L, Rizzo R, Debes NM, Nagy P, Cavanna AE, Termine C, Ganos C, Munchau A, Szejko N, Cath D, Muller-Vahl KR, Verdellen C, Hartmann A, Rothenberger A, Hoekstra PJ, Plessen KJ. European clinical guidelines for Tourette syndrome and other tic disorders-version 2.0. Part III: pharmacological treatment. Eur Child Adolesc Psychiatry. 2022 Mar;31(3):425-441. doi: 10.1007/s00787-021-01899-z. Epub 2021 Nov 10.

  PMID: 34757514 BACKGROUND

• Reese HE, Scahill L, Peterson AL, Crowe K, Woods DW, Piacentini J, Walkup JT, Wilhelm S. The premonitory urge to tic: measurement, characteristics, and correlates in older adolescents and adults. Behav Ther. 2014 Mar;45(2):177-86. doi: 10.1016/j.beth.2013.09.002. Epub 2013 Sep 21.

  PMID: 24491193 BACKGROUND

• McGuire JF, Piacentini J, Storch EA, Murphy TK, Ricketts EJ, Woods DW, Walkup JW, Peterson AL, Wilhelm S, Lewin AB, McCracken JT, Leckman JF, Scahill L. A multicenter examination and strategic revisions of the Yale Global Tic Severity Scale. Neurology. 2018 May 8;90(19):e1711-e1719. doi: 10.1212/WNL.0000000000005474. Epub 2018 Apr 13.

  PMID: 29653992 BACKGROUND

• McGuire JF, Karkanias GB, Bittman RM, Atkinson SD, Munschauer FE, Wanaski SP, Cunniff TM, Gilbert DL. Determining Clinically Meaningful Improvement in Children and Adolescents with Tourette Syndrome Receiving Pharmacotherapy. J Child Adolesc Psychopharmacol. 2025 Oct;35(8):447-453. doi: 10.1089/cap.2025.0036. Epub 2025 May 28.

  PMID: 40272969 BACKGROUND

• Sallee F, Kohegyi E, Zhao J, McQuade R, Cox K, Sanchez R, van Beek A, Nyilas M, Carson W, Kurlan R. Randomized, Double-Blind, Placebo-Controlled Trial Demonstrates the Efficacy and Safety of Oral Aripiprazole for the Treatment of Tourette's Disorder in Children and Adolescents. J Child Adolesc Psychopharmacol. 2017 Nov;27(9):771-781. doi: 10.1089/cap.2016.0026. Epub 2017 Jul 7.

  PMID: 28686474 BACKGROUND

• Steuber ER, McGuire JF. A meta-analysis of transcranial magnetic stimulation in Tourette syndrome. J Psychiatr Res. 2024 May;173:34-40. doi: 10.1016/j.jpsychires.2024.02.057. Epub 2024 Mar 8.

  PMID: 38479346 BACKGROUND

• Wu SW, Maloney T, Gilbert DL, Dixon SG, Horn PS, Huddleston DA, Eaton K, Vannest J. Functional MRI-navigated repetitive transcranial magnetic stimulation over supplementary motor area in chronic tic disorders. Brain Stimul. 2014 Mar-Apr;7(2):212-8. doi: 10.1016/j.brs.2013.10.005. Epub 2013 Oct 29.

  PMID: 24268723 BACKGROUND

• Fu M, Wei H, Meng X, Chen H, Shang B, Chen F, Huang Z, Sun Y, Wang Y. Effects of Low-Frequency Repetitive Transcranial Magnetic Stimulation of the Bilateral Parietal Cortex in Patients With Tourette Syndrome. Front Neurol. 2021 Feb 12;12:602830. doi: 10.3389/fneur.2021.602830. eCollection 2021.

  PMID: 33643191 BACKGROUND

• Wall CA, Croarkin PE, McClintock SM, Murphy LL, Bandel LA, Sim LA, Sampson SM. Neurocognitive effects of repetitive transcranial magnetic stimulation in adolescents with major depressive disorder. Front Psychiatry. 2013 Dec 12;4:165. doi: 10.3389/fpsyt.2013.00165. eCollection 2013.

  PMID: 24376426 BACKGROUND

• Seewoo BJ, Hennessy LA, Jaeschke LA, Mackie LA, Etherington SJ, Dunlop SA, Croarkin PE, Rodger J. A Preclinical Study of Standard Versus Accelerated Transcranial Magnetic Stimulation for Depression in Adolescents. J Child Adolesc Psychopharmacol. 2022 Apr;32(3):187-193. doi: 10.1089/cap.2021.0100. Epub 2021 Dec 31.

  PMID: 34978846 BACKGROUND

• Croarkin PE, Elmaadawi AZ, Aaronson ST, Schrodt GR Jr, Holbert RC, Verdoliva S, Heart KL, Demitrack MA, Strawn JR. Left prefrontal transcranial magnetic stimulation for treatment-resistant depression in adolescents: a double-blind, randomized, sham-controlled trial. Neuropsychopharmacology. 2021 Jan;46(2):462-469. doi: 10.1038/s41386-020-00829-y. Epub 2020 Sep 12.

  PMID: 32919400 BACKGROUND

• Gu LM, Deng CJ, Shang DW, Huang SQ, Nie S, Yang XH, Ning YP, Huang XB, Balbuena L, Xiang YT, Zheng W. Efficacy and safety of low-frequency repetitive transcranial magnetic stimulation in adolescents with first-episode major depressive disorder: A randomized, double-blind, sham-controlled pilot trial. J Affect Disord. 2025 Feb 1;370:190-197. doi: 10.1016/j.jad.2024.11.001. Epub 2024 Nov 2.

  PMID: 39491681 BACKGROUND

• Zewdie E, Ciechanski P, Kuo HC, Giuffre A, Kahl C, King R, Cole L, Godfrey H, Seeger T, Swansburg R, Damji O, Rajapakse T, Hodge J, Nelson S, Selby B, Gan L, Jadavji Z, Larson JR, MacMaster F, Yang JF, Barlow K, Gorassini M, Brunton K, Kirton A. Safety and tolerability of transcranial magnetic and direct current stimulation in children: Prospective single center evidence from 3.5 million stimulations. Brain Stimul. 2020 May-Jun;13(3):565-575. doi: 10.1016/j.brs.2019.12.025. Epub 2019 Dec 30.

  PMID: 32289678 BACKGROUND

• Allen CH, Kluger BM, Buard I. Safety of Transcranial Magnetic Stimulation in Children: A Systematic Review of the Literature. Pediatr Neurol. 2017 Mar;68:3-17. doi: 10.1016/j.pediatrneurol.2016.12.009. Epub 2017 Jan 4.

  PMID: 28216033 BACKGROUND

• Krishnan C, Santos L, Peterson MD, Ehinger M. Safety of noninvasive brain stimulation in children and adolescents. Brain Stimul. 2015 Jan-Feb;8(1):76-87. doi: 10.1016/j.brs.2014.10.012. Epub 2014 Oct 28.

  PMID: 25499471 BACKGROUND

• Stultz DJ, Osburn S, Burns T, Pawlowska-Wajswol S, Walton R. Transcranial Magnetic Stimulation (TMS) Safety with Respect to Seizures: A Literature Review. Neuropsychiatr Dis Treat. 2020 Dec 7;16:2989-3000. doi: 10.2147/NDT.S276635. eCollection 2020.

  PMID: 33324060 BACKGROUND

• Lerner AJ, Wassermann EM, Tamir DI. Seizures from transcranial magnetic stimulation 2012-2016: Results of a survey of active laboratories and clinics. Clin Neurophysiol. 2019 Aug;130(8):1409-1416. doi: 10.1016/j.clinph.2019.03.016. Epub 2019 Apr 6.

  PMID: 31104898 BACKGROUND

• Tao YJ, Duan XX, Liu P, Wang MW, Li SX, Luo TT, Xing HY, Huang Y. Efficacy and safety of repetitive transcranial magnetic stimulation in youth with depression: a systematic review and meta-analysis of randomized sham-controlled trials. World J Pediatr. 2025 Dec;21(12):1258-1274. doi: 10.1007/s12519-025-00983-7. Epub 2025 Oct 25.

  PMID: 41137879 BACKGROUND

• Croarkin PE, Aaronson ST, Carpenter LL, Hutton TM, Pages K, Chen B, Sackeim HA. The Effectiveness of Transcranial Magnetic Stimulation in Adolescents and Young Adults With Major Depressive Disorder. JAACAP Open. 2025 Jul 1;3(4):1246-1258. doi: 10.1016/j.jaacop.2025.06.006. eCollection 2025 Dec.

  PMID: 41367968 BACKGROUND

• Srivastava AV, Nemeroff CB, O'Sullivan SJ. TMS in adolescent depression: A milestone FDA clearance. Mol Psychiatry. 2026 Jun;31(6):3254-3256. doi: 10.1038/s41380-026-03455-0. Epub 2026 Feb 10. No abstract available.

  PMID: 41667837 BACKGROUND

• Cole EJ, Phillips AL, Bentzley BS, Stimpson KH, Nejad R, Barmak F, Veerapal C, Khan N, Cherian K, Felber E, Brown R, Choi E, King S, Pankow H, Bishop JH, Azeez A, Coetzee J, Rapier R, Odenwald N, Carreon D, Hawkins J, Chang M, Keller J, Raj K, DeBattista C, Jo B, Espil FM, Schatzberg AF, Sudheimer KD, Williams NR. Stanford Neuromodulation Therapy (SNT): A Double-Blind Randomized Controlled Trial. Am J Psychiatry. 2022 Feb;179(2):132-141. doi: 10.1176/appi.ajp.2021.20101429. Epub 2021 Oct 29.

  PMID: 34711062 BACKGROUND

• Blumberger DM, Vila-Rodriguez F, Thorpe KE, Feffer K, Noda Y, Giacobbe P, Knyahnytska Y, Kennedy SH, Lam RW, Daskalakis ZJ, Downar J. Effectiveness of theta burst versus high-frequency repetitive transcranial magnetic stimulation in patients with depression (THREE-D): a randomised non-inferiority trial. Lancet. 2018 Apr 28;391(10131):1683-1692. doi: 10.1016/S0140-6736(18)30295-2. Epub 2018 Apr 26.

  PMID: 29726344 BACKGROUND

• Wilhelm S, Peterson AL, Piacentini J, Woods DW, Deckersbach T, Sukhodolsky DG, Chang S, Liu H, Dziura J, Walkup JT, Scahill L. Randomized trial of behavior therapy for adults with Tourette syndrome. Arch Gen Psychiatry. 2012 Aug;69(8):795-803. doi: 10.1001/archgenpsychiatry.2011.1528.

  PMID: 22868933 BACKGROUND

• Piacentini J, Woods DW, Scahill L, Wilhelm S, Peterson AL, Chang S, Ginsburg GS, Deckersbach T, Dziura J, Levi-Pearl S, Walkup JT. Behavior therapy for children with Tourette disorder: a randomized controlled trial. JAMA. 2010 May 19;303(19):1929-37. doi: 10.1001/jama.2010.607.

  PMID: 20483969 BACKGROUND

• Halvorsen MW. Tourette Syndrome and Chronic Tic Disorders. Psychiatr Clin North Am. 2025 Jun;48(2):281-292. doi: 10.1016/j.psc.2025.01.006. Epub 2025 Mar 4.

  PMID: 40348418 BACKGROUND

• Johnco C, McGuire JF, McBride NM, Murphy TK, Lewin AB, Storch EA. Suicidal ideation in youth with tic disorders. J Affect Disord. 2016 Aug;200:204-11. doi: 10.1016/j.jad.2016.04.027. Epub 2016 Apr 23.

  PMID: 27136419 BACKGROUND

• Weingarden H, Scahill L, Hoeppner S, Peterson AL, Woods DW, Walkup JT, Piacentini J, Wilhelm S. Self-esteem in adults with Tourette syndrome and chronic tic disorders: The roles of tic severity, treatment, and comorbidity. Compr Psychiatry. 2018 Jul;84:95-100. doi: 10.1016/j.comppsych.2018.04.008. Epub 2018 Apr 23.

  PMID: 29729555 BACKGROUND

• Ricketts EJ, Woods DW, Espil FM, McGuire JF, Stiede JT, Schild J, Yadegar M, Bennett SM, Specht MW, Chang S, Scahill L, Wilhelm S, Peterson AL, Walkup JT, Piacentini J. Childhood Predictors of Long-Term Tic Severity and Tic Impairment in Tourette's Disorder. Behav Ther. 2022 Nov;53(6):1250-1264. doi: 10.1016/j.beth.2022.07.002. Epub 2022 Jul 16.

  PMID: 36229120 BACKGROUND

• Scahill L, Specht M, Page C. The Prevalence of Tic Disorders and Clinical Characteristics in Children. J Obsessive Compuls Relat Disord. 2014 Oct 1;3(4):394-400. doi: 10.1016/j.jocrd.2014.06.002.

  PMID: 25436183 BACKGROUND

• Yilmaz AY, Jankovic J. Epidemiology of Tourette Syndrome. Brain Sci. 2025 Apr 22;15(5):426. doi: 10.3390/brainsci15050426.

  PMID: 40426597 BACKGROUND

• Black KJ, Kim S, Yang NY, Greene DJ. Course of tic disorders over the lifespan. Curr Dev Disord Rep. 2021 Jun;8(2):121-132. doi: 10.1007/s40474-021-00231-3. Epub 2021 Apr 10.

  PMID: 34178575 BACKGROUND

MeSH Terms

Conditions

Tic Disorders; Tics

Condition Hierarchy (Ancestors)

Movement Disorders; Central Nervous System Diseases; Nervous System Diseases; Neurodevelopmental Disorders; Mental Disorders; Dyskinesias; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Andrew M Lee

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Andrew M Lee

CONTACT

415-476-7000; AndrewMoses.Lee@ucsf.edu

James T McCracken

CONTACT

415-514-5743; James.Mccracken@ucsf.edu

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 14, 2026
• First Posted: September 24, 2026
• Study Start: June 1, 2026
• Primary Completion (Estimated): June 1, 2028
• Study Completion (Estimated): October 1, 2028
• Last Updated: September 24, 2026

Record last verified: 2026-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)