Starting soon
Phase 1
Transcranial Magnetic Stimulation for Depression in Multiple Sclerosis
Condition(s) studied
Multiple SclerosisDepression - Major Depressive DisorderFatigue
Investigational drug(s) / intervention(s)
Repetitive Transcranial Magnetic Stimulation (rTMS)
Repetitive Transcranial Magnetic Stimulation (rTMS): 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).
Study 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.
Eligibility
Inclusion Criteria:
1. 18-65 years of age, inclusive.
2. Males, females, and non-binary.
3. 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.
4. Expanded Disability Status Scale score \<7.
5. Fatigue Severity Scale ≥ 4.
6. Moderate to severe major depressive disorder as defined by a Hamilton Depression Rating Scale-17 item score ≥18.
7. Did not benefit adequately from ≥ 1 antidepressant or course of psychotherapy.
8. Stable immunotherapy for at least 3 months and medications for at least 4 weeks.
9. Have no contraindications to TMS or magnetic resonance imaging.
10. 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.
11. Are able to adhere to the treatment schedule
12. Pass the TMS adult safety screening (TASS) questionnaire
Exclusion Criteria:
1. 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.
2. 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.
3. History of seizures.
4. 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).
5. Previous surgeries opening the skull leaving skull defects capable of allowing the insertion of a cylinder with a radius ≥ 5mm.
6. Any diagnosis of a psychiatric diagnosis determined to be primary.
7. Are at a significant risk of harm to themselves or others.
8. Have a substance or alcohol use disorder within the last three months.
9. 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.
10. Are currently pregnant, breast feeding, or plan to become pregnant over the duration of the study.
11. Active suicidal ideation as defined by a score of 4 ≥ on item 10 of MADRS
12. Have failed a course of ECT in the current episode. Previous ECT treatment outside of the current episode does not influence inclusion.
13. 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
14. Have concomitant major unstable medical illness
Primary outcome measure(s)
- Presence of demyelinating lesions within the TMS-induced electric field and downstream projections (Safety) — Baseline (prior to intervention)
Overlap between individualized TMS electric field modeling and demyelinating lesions identified on MRI, including cortical target and tractography-defined downstream pathways.
- Clinical Global Impression-Severity and -Improvement scales (CGI-S, CGI-I) — Baseline, Day 5 (post-treatment), and 4-week follow-up
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.
- Montgomery-Åsberg Depression Rating Scale (MADRS) — Baseline, Day 5 (post-treatment), and 4-week follow-up
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).
- 17-item Hamilton Rating Scale for Depression (HAM-D-17) — Baseline, Day 5 (post-treatment), and 4-week follow-up
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.
- Columbia-Suicide Severity Rating Scale (C-SSRS). — Baseline, Day 5 (post-treatment), and 4-week follow-up
The Columbia-Suicide Severity Rating Scale (C-SSRS) is a questionnaire used for suicide assessment
Trial sites (1)
| Facility | City | Region | Status |
|---|
| Foothills Medical Centre |
Calgary |
Alberta |
|
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