Transcranial Magnetic Stimulation for Depression in Multiple Sclerosis

NCT07562074 | Not Yet Recruiting Phase 1

• 1 other identifier: REB25-0285
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

Canada has one of the highest rates of multiple sclerosis (MS). MS patients experience disabling motor, visual, and sensory symptoms, and a high risk of comorbid major depressive disorder (MDD) and severe fatigue. The lifetime prevalence of MDD in MS patients is about 50%, and nearly 90% experience severe fatigue, both of which are not responsive to typical treatments. Repetitive transcranial magnetic stimulation (rTMS) is a first line, Health Canada approved non-invasive neurostimulation treatment for MDD. rTMS induces electrical activity in the cortex using magnetic fields generated outside of the head to drive neuronal firing in the target site. However, MS is typically an exclusion criterion due to safety concerns. The goal of this clinical trial is to learn if repeated transcranial magnetic stimulation (rTMS) can be used to treat depression symptoms in adults with multiple sclerosis (MS). rTMS is a non-invasive form of brain stimulation that uses magnetic pulses to stimulate specific parts of the brain. The main questions it aims to answer are: Is rTMS safe, tolerable, and feasible to deliver as a treatment for depression and fatigue symptoms in individuals with MS? Does rTMS show preliminary effectiveness in improving depression and fatigue symptoms in this population? Researchers will determine whether rTMS treatment improves mood, fatigue, and cognition across time points (baseline, after treatment, and 4-week follow-up). Participants will: Complete screening, questionnaires, clinical assessments, cognitive tests, a brain MRI to help tailor the TMS treatment, and receive daily TMS sessions for 5 consecutive days, including: Pre-TMS brain mapping, five rTMS treatments (3 minutes) per day, separated by one hour. A safety and tolerability questionnaire will be administered daily. Complete post-treatment assessments (questionnaires, cognitive tests, psychiatric evaluation). Complete a 4-week follow-up visit, in person or virtually. Wear a fitness tracking watch during the study so researchers can collect activity data remotely. About 20 people will take part in this study through the University of Calgary.

Conditions

Multiple Sclerosis; Depression - Major Depressive Disorder; Fatigue

Keywords

Multiple Sclerosis; TMS; rTMS; Depression; Brain Stimulation

Outcome Measures

Primary Outcomes (5)

• Presence of demyelinating lesions within the TMS-induced electric field and downstream projections (Safety)

  Overlap between individualized TMS electric field modeling and demyelinating lesions identified on MRI, including cortical target and tractography-defined downstream pathways.

  Baseline (prior to intervention)

• Clinical Global Impression-Severity and -Improvement scales (CGI-S, CGI-I)

  The CGI provides an overall clinician-determined summary measure that takes into account all available information, including a knowledge of the patient's history, psychosocial circumstances, symptoms, behavior, and the impact of the symptoms on the patient's ability to function.

  Baseline, Day 5 (post-treatment), and 4-week follow-up

• Montgomery-Åsberg Depression Rating Scale (MADRS)

  The Montgomery-Asberg Rating Scale (MADRS) is a 10-item clinician-rated assessment for depression in adults (18+). The MADRS focusses more upon functional impairment and somatic symptoms than other assessments which might focus more upon depressive cognitive attitudes (Montgomery and Asberg, 1979).

  Baseline, Day 5 (post-treatment), and 4-week follow-up

• 17-item Hamilton Rating Scale for Depression (HAM-D-17)

  The 17-item Hamilton Rating Scale for Depression (HAM-D-17) is a widely used clinician-rated tool to assess the severity of depressive symptoms, focusing on mood, guilt, suicide, insomnia, work/activity, retardation, agitation, anxiety, somatic symptoms, and weight loss.

  Baseline, Day 5 (post-treatment), and 4-week follow-up

• Columbia-Suicide Severity Rating Scale (C-SSRS).

  The Columbia-Suicide Severity Rating Scale (C-SSRS) is a questionnaire used for suicide assessment

  Baseline, Day 5 (post-treatment), and 4-week follow-up

Secondary Outcomes (9)

• TMS Safety and Tolerability

  Daily during the 5-day treatment period and at post-treatment assessment (Day 5)

• Fitness watch data

  Watches will be given at the baseline session and be worn until the last follow-up session. (4 weeks after the intervention).

• The Quick Inventory of Depressive Symptomatology - Self-Report (QIDS-SR)

  Time Frame: Baseline, Day 5 (post-treatment), 4-week follow-up

• Generalized Anxiety Disorder 7-item scale (GAD-7)

  Time Frame: Baseline, Day 5 (post-treatment), 4-week follow-up

• Scale for Suicidal Ideation (SSI)

  Time Frame: Baseline, Day 5 (post-treatment), 4-week follow-up

Study Arms (1)

Stimulation to the Left Dorsolateral Prefrontal Cortex (DLPFC)

EXPERIMENTAL

Participants will receive intermittent theta burst stimulation (iTBS) targeting the left dorsolateral prefrontal cortex (Magstim D70 AFC Air Film coil). Prior to treatment, participants will undergo magnetic resonance imaging and individualized electric field modeling to ensure that the stimulation target and its downstream projections do not overlap with demyelinating lesions. iTBS will be delivered at 80% of resting motor threshold, consisting of 600 pulses per session administered as triplets at 50 Hz repeated at 5 Hz. Treatments will be delivered five times per day, with a one-hour inter-session interval, over five consecutive weekdays. Clinical, cognitive, and neurophysiological outcome measures will be assessed at baseline, post-treatment, and at -week follow-up to evaluate safety, feasibility, and preliminary clinical effects.

Device: Repetitive Transcranial Magnetic Stimulation (rTMS)

Interventions

Repetitive Transcranial Magnetic Stimulation (rTMS) DEVICE

Treatment of iTBS for 5 consecutive days. iTBS will involve 600 pulses per session delivered as triplets of 50Hz repeated at 5Hz at 80% resting motor threshold (rMT).

Stimulation to the Left Dorsolateral Prefrontal Cortex (DLPFC)

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• years of age, inclusive.
• Males, females, and non-binary.
• Clinical diagnosis of relapsing-remitting or primary-progressive multiple sclerosis according to the revised McDonald criteria and as determined by the study neurologist and medical records.
• Expanded Disability Status Scale score \<7.
• Fatigue Severity Scale ≥ 4.
• Moderate to severe major depressive disorder as defined by a Hamilton Depression Rating Scale-17 item score ≥18.
• Did not benefit adequately from ≥ 1 antidepressant or course of psychotherapy.
• Stable immunotherapy for at least 3 months and medications for at least 4 weeks.
• Have no contraindications to TMS or magnetic resonance imaging.
• Ability to provide written consent obtained from study subject or subject's legal representative and ability for study subject to comply with the requirements of the study.
• Are able to adhere to the treatment schedule
• Pass the TMS adult safety screening (TASS) questionnaire

You may not qualify if:

• Presence of any disease, medical condition, or physical condition that, in the opinion of the study investigator, study psychiatrist, or study neurologist, may compromise interfere, limit, affect, or reduce the study subject's ability to complete the study.
• Presence of any disease, medical condition, or physical condition that, in the opinion of the study investigator, study psychiatrist, or study neurologist, may adversely impact the safety of the study subject or the integrity of the data.
• History of seizures.
• Any cranial metal implants (excluding ≤ 1mm thick epicranial titanium skull plates and dental fillings) or medical devices (i.e. cardiac pacemaker, deep brain stimulator, medication infusion pump, cochlear implant).
• Previous surgeries opening the skull leaving skull defects capable of allowing the insertion of a cylinder with a radius ≥ 5mm.
• Any diagnosis of a psychiatric diagnosis determined to be primary.
• Are at a significant risk of harm to themselves or others.
• Have a substance or alcohol use disorder within the last three months.
• If participating in psychotherapy, must have been in stable treatment for at least three months prior to entry into the study, with no anticipation of change in the frequency of therapeutic sessions, or the therapeutic focus over the duration of the study.
• Are currently pregnant, breast feeding, or plan to become pregnant over the duration of the study.
• Active suicidal ideation as defined by a score of 4 ≥ on item 10 of MADRS
• Have any significant neurological disorder or insult including, but not limited to: any condition likely to be associated with increased intracranial pressure, space occupying brain lesion, any history of epilepsy, cerebral aneurysm, Parkinson's disease, Huntington's chorea, significant head trauma with loss of consciousness for greater than or equal to 5 minutes
• Have concomitant major unstable medical illness

Sponsors & Collaborators

• University of Calgary: lead
• Hotchkiss Brain Institute, University of Calgary: collaborator

Study Sites (1)

Foothills Medical Centre

Calgary, Alberta, T2N 2T9, Canada

Location

Related Publications (4)

• Ahmadpanah M, Amini S, Mazdeh M, Haghighi M, Soltanian A, Jahangard L, Keshavarzi A, Brand S. Effectiveness of Repetitive Transcranial Magnetic Stimulation (rTMS) Add-On Therapy to a Standard Treatment in Individuals with Multiple Sclerosis and Concomitant Symptoms of Depression-Results from a Randomized Clinical Trial and Pilot Study. J Clin Med. 2023 Mar 27;12(7):2525. doi: 10.3390/jcm12072525.

  PMID: 37048608 BACKGROUND

• Siegert RJ, Abernethy DA. Depression in multiple sclerosis: a review. J Neurol Neurosurg Psychiatry. 2005 Apr;76(4):469-75. doi: 10.1136/jnnp.2004.054635.

  PMID: 15774430 BACKGROUND

• Rossi S, Antal A, Bestmann S, Bikson M, Brewer C, Brockmoller J, Carpenter LL, Cincotta M, Chen R, Daskalakis JD, Di Lazzaro V, Fox MD, George MS, Gilbert D, Kimiskidis VK, Koch G, Ilmoniemi RJ, Lefaucheur JP, Leocani L, Lisanby SH, Miniussi C, Padberg F, Pascual-Leone A, Paulus W, Peterchev AV, Quartarone A, Rotenberg A, Rothwell J, Rossini PM, Santarnecchi E, Shafi MM, Siebner HR, Ugawa Y, Wassermann EM, Zangen A, Ziemann U, Hallett M; basis of this article began with a Consensus Statement from the IFCN Workshop on "Present, Future of TMS: Safety, Ethical Guidelines", Siena, October 17-20, 2018, updating through April 2020. Safety and recommendations for TMS use in healthy subjects and patient populations, with updates on training, ethical and regulatory issues: Expert Guidelines. Clin Neurophysiol. 2021 Jan;132(1):269-306. doi: 10.1016/j.clinph.2020.10.003. Epub 2020 Oct 24.

  PMID: 33243615 BACKGROUND

• Uygur-Kucukseymen E, Pacheco-Barrios K, Yuksel B, Gonzalez-Mego P, Soysal A, Fregni F. Non-invasive brain stimulation on clinical symptoms in multiple sclerosis patients: A systematic review and meta-analysis. Mult Scler Relat Disord. 2023 Oct;78:104927. doi: 10.1016/j.msard.2023.104927. Epub 2023 Aug 4.

  PMID: 37595371 BACKGROUND

MeSH Terms

Conditions

Multiple Sclerosis; Fatigue; Depression

Interventions

Transcranial Magnetic Stimulation

Condition Hierarchy (Ancestors)

Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Behavioral Symptoms; Behavior

Intervention Hierarchy (Ancestors)

Magnetic Field Therapy; Therapeutics

Study Officials

• Adrianna Giuffre, PhD.

  Cumming School of Medicine, University of Calgary

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Anna L Bourgeois, MSc.

CONTACT

4039887901; anna.bourgeois@ucalgary.ca

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor, Cumming School of Medicine, Department of Psychiatry

Study Record Dates

• First Submitted: January 6, 2026
• First Posted: May 1, 2026
• Study Start (Estimated): June 15, 2026
• Primary Completion (Estimated): June 30, 2027
• Study Completion (Estimated): December 30, 2027
• Last Updated: May 1, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)