Impact of Spaced iTBS on Plasticity in the Motor Cortex

NCT06735794 | Completed

• 1 other identifier: 2023/218
• Study Type: interventional
• Target: 29
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical trial is to explore the effects of non-invasive brain stimulation protocols using intermittent theta-burst stimulation (iTBS) on brain plasticity in healthy, right-handed individuals aged 18 to 50 years. Brain plasticity is the brain's ability to change through growth or reorganization. iTBS is a form of transcranial magnetic stimulation (TMS), where magnetic pulses are applied to the scalp using a coil. These pulses pass through the scalp, and can alter brain activity in the area underneath the coil. Based on previous research conducted in animals and humans, researchers believe that iTBS can strengthen the connections between cells in the brain, leading to improved brain plasticity. This trial will compare the effects of the compressed iTBS (iTBS-c) protocol, which is commonly used to treat depression, and the spaced iTBS (iTBS-s) protocol. Researchers want to find out which protocol is better able to produce changes in brain plasticity. Sham iTBS (iTBS-sh) will be used as a control to make the results of the study more reliable. Participants will complete 5 study visits within the span of 3 months, including:

• Screening assessments to determine eligibility (Visit 1);
• Calibration iTBS session (Visit 2) to assess tolerability of brain stimulation;
• Three experimental iTBS sessions (iTBS-s, iTBS-c, and iTBS-sh) in a randomized order (Visits 3-5), each separated by at least 72 hours. During each session, the study team will stimulate the motor cortex and record the muscle activity of your hand to measure changes in brain plasticity.

Conditions

Healthy Control Subjects

Keywords

TMS; TBS; Brain stimulation; Healthy; Control; Healthy individuals; Transcranial Magnetic Stimulation; Intermittent Theta-Burst Stimulation; Motor Cortex; Neuroplasticity; Brain plasticity; Cortical plasticity; iTBS; iTBS-c; iTBS-s; iTBS-sh; Spaced iTBS; Compressed iTBS; Sham iTBS; LTP; Long Term Potentiation; Theta-Burst Stimulation

Outcome Measures

Primary Outcomes (1)

• iTBS-LTP

  The primary outcome measure is iTBS-induced LTP (iTBS-LTP), which will be calculated at each post-iTBS time points (Post-0, Post-15, Post-30, Post-45 and Post-60). At each time point, the mean or median MEP amplitude will be divided by the mean or median MEP amplitude across the two pre-iTBS TMS measurements (Pre-30 and Pre-15) for the corresponding iTBS condition. This will be repeated for all three iTBS conditions to generate iTBS-LTP values at the five post-iTBS time points. Larger iTBS-LTP values are indicative of stronger plasticity following the intervention. This will address hypothesis 1, which examines whether iTBS-s induces stronger iTBS-LTP compared to iTBS-c, and hypothesis 2, which evaluates whether iTBS-s and iTBS-c induce stronger iTBS-LTP compared to iTBS-sh.

  Up to 3 months

Study Arms (3)

Compressed iTBS

ACTIVE COMPARATOR

After completing Visits 1-2 (Screening and Calibration), participants will undergo the iTBS-c condition in a randomized order during Visits 3 to 5. iTBS-c is the active comparator.

Device: Compressed iTBS

Spaced iTBS

EXPERIMENTAL

After completing Visits 1-2 (Screening and Calibration), participants will undergo the iTBS-s condition in a randomized order during Visits 3 to 5. iTBS-s is the experimental study intervention.

Device: Spaced iTBS

Sham iTBS

SHAM COMPARATOR

After completing Visits 1-2 (Screening and Calibration), participants will undergo the iTBS-sh condition in a randomized order during Visits 3 to 5. iTBS-sh is the sham comparator.

Device: Sham iTBS

Interventions

Compressed iTBS DEVICE

Intermittent Theta-Burst Stimulation (iTBS) is a form of non-invasive brain stimulation that uses magnetic pulses applied to the scalp using a coil. iTBS will be used to stimulate the left motor cortex to enhance long-term potentiation (LTP)-like activity, a physiological mechanism associated with brain plasticity. During the intervention, the study team will conduct two pre-iTBS TMS measurements (Pre-30 and Pre-15). Participants will then complete iTBS-c (active comparator), which will be delivered unilaterally to the left motor cortex. Following iTBS-c, five post-iTBS TMS measurements (Post-0, 15, 30, 45, and 60) will be obtained. Motor evoked potentials (MEPs) will be recorded from the right APB, ADM, and FDI muscles to assess the effects of the stimulation. The MCF-B65, MCF-P-B65, and/or Cool-B65 A/P TMS coils will be used, alongside the MagPro R30 or the MagPro X100 TMS stimulators to deliver the intervention.

Also known as: iTBS-c

Compressed iTBS

Spaced iTBS DEVICE

Intermittent Theta-Burst Stimulation (iTBS) is a form of non-invasive brain stimulation that uses magnetic pulses applied to the scalp using a coil. iTBS will be used to stimulate the left motor cortex to enhance long-term potentiation (LTP)-like activity, a physiological mechanism associated with brain plasticity. During the intervention, the study team will conduct two pre-iTBS TMS measurements (Pre-30 and Pre-15). Participants will then complete iTBS-s (experimental study intervention), which will be delivered unilaterally to the left motor cortex. Following iTBS-s, five post-iTBS TMS measurements (Post-0, 15, 30, 45, and 60) will be obtained. Motor evoked potentials (MEPs) will be recorded from the right APB, ADM, and FDI muscles to assess the effects of the stimulation. The MCF-B65, MCF-P-B65, and/or Cool-B65 A/P TMS coils will be used, alongside the MagPro R30 or the MagPro X100 TMS stimulators to deliver the intervention.

Also known as: iTBS-s

Spaced iTBS

Sham iTBS DEVICE

Intermittent Theta-Burst Stimulation (iTBS) is a form of non-invasive brain stimulation that uses magnetic pulses applied to the scalp using a coil. iTBS will be used to stimulate the left motor cortex to enhance long-term potentiation (LTP)-like activity, a physiological mechanism associated with brain plasticity. During the intervention, the study team will conduct two pre-iTBS TMS measurements (Pre-30 and Pre-15). Participants will then complete iTBS-sh (sham comparator), which will be delivered unilaterally to the left motor cortex. Following iTBS-sh, five post-iTBS TMS measurements (Post-0, 15, 30, 45, and 60) will be obtained. Motor evoked potentials (MEPs) will be recorded from the right APB, ADM, and FDI muscles to assess the effects of the stimulation. The MCF-B65, MCF-P-B65, and/or Cool-B65 A/P TMS coils will be used, alongside the MagPro R30 or the MagPro X100 TMS stimulators to deliver the intervention.

Also known as: iTBS-sh

Sham iTBS

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Age 18 years or above, and less than 51 years.
• Right handedness, assessed using the Edinburgh Handedness Inventory (EHI).
• Sufficiently proficient in English to complete the required study assessments, as per investigator judgement.
• Willingness and capacity to provide informed consent.
• Willingness to comply with all study procedures.

You may not qualify if:

• Age 17 years or less, or greater than 51 years, as brain plasticity is known to be affected by age.
• Current use of any psychotropic medications (e.g. anti-depressants, anti-convulsants, anti-psychotics, etc.).
• Contraindications to transcranial magnetic stimulation (TMS), as per investigator judgment.
• Lifetime history of any Diagnostic and Statistical Manual of Mental Disorders (DSM-5) diagnosis, assessed using the Structured Clinical Interview for DSM-5 (SCID-5), except simple phobias.
• Left handed or ambidextrous, assessed using the EHI, to minimize the heterogeneity in cortical excitability and plasticity.
• Self-reported history of seizures and/or other major neurological conditions, as per investigator judgement, due to the risk of seizures associated with TMS in individuals with a heightened risk.

Sponsors & Collaborators

• Centre for Addiction and Mental Health: lead

Study Sites (1)

Centre for Addiction and Mental Health

Toronto, Ontario, M6J 1H4, Canada

Location

Related Publications (9)

• Berlim MT, McGirr A, Rodrigues Dos Santos N, Tremblay S, Martins R. Efficacy of theta burst stimulation (TBS) for major depression: An exploratory meta-analysis of randomized and sham-controlled trials. J Psychiatr Res. 2017 Jul;90:102-109. doi: 10.1016/j.jpsychires.2017.02.015. Epub 2017 Feb 21.

  PMID: 28254709 RESULT

• Chung SW, Hoy KE, Fitzgerald PB. Theta-burst stimulation: a new form of TMS treatment for depression? Depress Anxiety. 2015 Mar;32(3):182-92. doi: 10.1002/da.22335. Epub 2014 Nov 28.

  PMID: 25450537 RESULT

• Höflich G, Kasper S, Hufnagel A, Ruhrmann S, Möller HJ. Application of transcranial magnetic stimulation in treatment of drug-resistant major depression-a report of two cases. Human Psychopharmacology: Clinical and Experimental. 1993;8(5):361-365.

  RESULT

• George MS, Wassermann EM, Williams WA, Callahan A, Ketter TA, Basser P, Hallett M, Post RM. Daily repetitive transcranial magnetic stimulation (rTMS) improves mood in depression. Neuroreport. 1995 Oct 2;6(14):1853-6. doi: 10.1097/00001756-199510020-00008.

  PMID: 8547583 RESULT

• George MS, Lisanby SH, Avery D, McDonald WM, Durkalski V, Pavlicova M, Anderson B, Nahas Z, Bulow P, Zarkowski P, Holtzheimer PE 3rd, Schwartz T, Sackeim HA. Daily left prefrontal transcranial magnetic stimulation therapy for major depressive disorder: a sham-controlled randomized trial. Arch Gen Psychiatry. 2010 May;67(5):507-16. doi: 10.1001/archgenpsychiatry.2010.46.

  PMID: 20439832 RESULT

• Cantone M, Bramanti A, Lanza G, Pennisi M, Bramanti P, Pennisi G, Bella R. Cortical Plasticity in Depression. ASN Neuro. 2017 May-Jun;9(3):1759091417711512. doi: 10.1177/1759091417711512.

  PMID: 28629225 RESULT

• Vignaud P, Damasceno C, Poulet E, Brunelin J. Impaired Modulation of Corticospinal Excitability in Drug-Free Patients With Major Depressive Disorder: A Theta-Burst Stimulation Study. Front Hum Neurosci. 2019 Feb 26;13:72. doi: 10.3389/fnhum.2019.00072. eCollection 2019.

  PMID: 30863297 RESULT

• Liu W, Ge T, Leng Y, Pan Z, Fan J, Yang W, Cui R. The Role of Neural Plasticity in Depression: From Hippocampus to Prefrontal Cortex. Neural Plast. 2017;2017:6871089. doi: 10.1155/2017/6871089. Epub 2017 Jan 26.

  PMID: 28246558 RESULT

• Duman RS. Pathophysiology of depression: the concept of synaptic plasticity. Eur Psychiatry. 2002 Jul;17 Suppl 3:306-10. doi: 10.1016/s0924-9338(02)00654-5.

  PMID: 15177086 RESULT

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Masking Details: This clinical trial is a single-blinded study. Participants will be blinded to the iTBS condition they are receiving in Visits 2-5. The individual administering iTBS (i.e., the interventionist) will not be blinded to the iTBS condition being administered. To maintain participant blinding, each of the three iTBS interventions (iTBS-c, iTBS-s, and iTBS-sh) were designed to be similar in length and structure.
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This study will employ a randomized, single-blind cross-over design with three experimental iTBS conditions (iTBS-c, iTBS-s, and iTBS-sh).

Study Record Dates

• First Submitted: November 22, 2024
• First Posted: December 16, 2024
• Study Start: November 13, 2024
• Primary Completion: February 1, 2026
• Study Completion: February 1, 2026
• Last Updated: February 4, 2026

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)