Multiple SclerosisNCT04621708
Pilot Study of the Safety and Tolerability of L-DLPFC iTBS rTMS for MDD in MS
A study testing Repetitive transcranial magnetic stimulation in people with Multiple Sclerosis and Major Depressive Disorder, run by Sunnybrook Health Sciences Centre at 1 site in Canada.
Trial summary
The main purpose of this study is to investigate the safety and tolerability of intermittent Theta Burst (iTBS) repetitive transcranial magnetic stimulation (rTMS), its effectiveness in alleviating depressive symptoms as well as its effects on cognition. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Multiple Sclerosis, Major Depressive Disorder
- What is being tested?
- Repetitive transcranial magnetic stimulation
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteCanada
- Study dates
- 30 Apr 2020to 30 Apr 2024
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Men and women ≥18 and ≤70 years of age, inclusive.
- History of MS confirmed by a neurologist.
- Patients who are able and willing to give consent and able to adhere to treatment schedule and attend study visits, as determined by study psychiatrist
- DSM-V diagnosis of Major Depressive Disorder (MDD)
- Moderate severity with a Hamilton Depression Rating Scale (HAMD) at least 16
- Patients have had no increase or initiation of any psychotropic medication in the 4 weeks prior to screening
- Pass the TMS safety screening questionnaire
- Women of childbearing potential must agree to use a barrier contraception method throughout the study.
Who cannot join
- Active substance abuse or dependence in the last three months, except nicotine
- Active suicidal intent
- Currently pregnant (as determined by history and serum HCG) or lactating.
- A diagnosis of Bipolar Disorder
- A history of past or current psychotic symptoms
- Diagnosis of obsessive-compulsive disorder, post-traumatic stress disorder (current or within the last year), assessed by a study investigator to be primary and causing greater impairment than MDD
Show all 16Show fewer
- Having failed a course of ECT in the current episode or previous episode
- Previous trial of rTMS
- Personality disorder deemed to be primary pathology
- If participating in psychotherapy, must have been in stable treatment for at least 3 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
- Clinically significant laboratory abnormality, in the opinion of the investigator
- Unstable medical illness
- Contraindication to rTMS, e.g. presence of cardiac pacemaker, intracranial implant, or metal in the cranium
- Currently on more than 2 mg of lorazepam or equivalent
- History of seizures, or currently on anticonvulsant for seizures
- Concurrent use of a medication that may lower the seizure threshold, in the opinion of the investigator e.g. stimulant.
Trial locations and contacts
1 site in 1 country.
Canada1 site, 1 recruiting
- Recruiting
Sunnybrook Health Sciences Centre
Toronto, Ontario, M4N 3M5
Anusha Baskarna, PhD, 416-480-6100 ext. 1650, anusha.baskaran@sunnybrook.ca
About this study
Official title: Pilot Study of the Safety and Tolerability of Left Dorsolateral Prefrontal Cortex Intermittent Theta Burst rTMS for Major Depressive Disorder in Multiple Sclerosis
The main purpose of this study is to investigate the safety and tolerability of intermittent Theta Burst (iTBS) repetitive transcranial magnetic stimulation (rTMS), its effectiveness in alleviating depressive symptoms as well as its effects on cognition. Although iTBS rTMS is approved for use, there have been no safety and tolerability evaluations of this form of rTMS in Multiple Sclerosis (MS).
Read the detailed description
The main purpose of this study is to investigate the safety and tolerability of intermittent Theta Burst (iTBS), its effectiveness in alleviating depressive symptoms, concomitant neuropsychiatric symptoms such as anxiety and fatigue in people with MS, as well as its effects on cognition. Although iTBS repetitive transcranial magnetic stimulation (rTMS) is approved for use in major depressive disorder (MDD), there have been no safety and tolerability evaluations of this form of rTMS in Multiple Sclerosis (MS) patient with MDD. Although iTBS rTMS has previously been found safe and effective for treating spasticity in people with MS, this will be the first study to investigate the safety and tolerability of Left Dorsolateral Prefrontal Cortex (L-DLPFC) iTBS rTMS for MDD in MS
This study is designed as an open-label pilot study. Participants will undergo baseline evaluations to confirm a diagnosis of MDD and to assess your eligibility for rTMS treatment. If deemed eligible, participants will receive iTBS treatment. iTBS is a form of rTMS approved by Health Canada for treatment of MDD. iTBS rTMS treatment involves 3 minutes of non-invasive brain stimulation, 5 days a week, for 4 weeks, for a total of 20 treatments. While receiving iTBS rTMS, participants will be seen daily by the rTMS operator who is a mental health nurse. While receiving iTBS rTMS, participants will see the research coordinator and study psychiatrist on a weekly basis, to complete clinical assessments to evaluate their neuropsychiatric symptoms and assess any side effects from the rTMS procedure. As part of the suggested pathophysiological profile of depression the levels of inflammatory cytokines tumor necrosis factor ⍺ (TNF-⍺) and interleukin-6 (IL-6) have shown elevated concentration levels in plasma of depressed compared to non-depressed individuals. In this study, we aim to investigate the levels of these inflammatory cytokine markers and their change with iTBS.
- Conditions
- Multiple Sclerosis, Major Depressive Disorder
- Being tested
- Repetitive transcranial magnetic stimulation
- Keywords
- MS, MDD
- Medical subject headings
- Multiple Sclerosis, Depressive Disorder, Major
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Repetitive transcranial magnetic stimulationDevice
Left DLPFC iTBS rTMS
| Study group | Role | What they receive |
|---|---|---|
| Left DLPFC iTBS rTMS | Experimental | Not described Receives: Device: Repetitive transcranial magnetic stimulation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in depressive symptoms
The primary outcome measure will be the reduction in depressive symptoms as measured by the Hamilton Depression Rating Scale-17 at the end of the 4-week trial of iTBS rTMS. This will be measured as both a continuous variable (score on HAMD-17 at week 4 - score on HAMD-17 at week 0 pre-treatment) and a categorical one (i.e. the response rates of >50% reduction from baseline HAMD-17 and remission rates defined as HAMD-17 <7).
Measured: Baseline and 4 weeks post-treatment
Secondary outcomes (5)
Change in anxiety and depressive symptoms
Change in anxiety and depressive symptoms as measured by the self-report Hospital Anxiety and Depression Scale (HADS)-17 at the end of the 4-week trial of iTBS rTMS.
Measured: Baseline and 4 weeks post-treatment
Change in fatigue, severity and impact
Change in fatigue, severity and impact, measured by the self-report Fatigue Severity Scale (FSS)
Measured: Baseline and 4 weeks post-treatment
Change in Neuropsychological function
Change in Neuropsychological function, measured subjectively through the Perceived Deficits Questionnaire (PDQ-5) and objectively by the SDMT and computerized CANTAB neuropsychological tasks
Measured: Baseline and 4 weeks post-treatment
Change in fatigue, severity and impact
Change in fatigue, severity and impact, measured by the Modified Fatigue Impact Scale (MFIS), respectively
Measured: Baseline and 4 weeks post-treatment
Change in Neuropsychological function
Change in Neuropsychological function, measured objectively by the computerized CANTAB neuropsychological tasks
Measured: Baseline and 4 weeks post-treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Nov 2020
- Study start30 Apr 2020
- Primary completion30 Apr 2024 (estimated)
- Study completion30 Apr 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Multiple SclerosisStudies of the same condition, open and under way.
- More trials run by Sunnybrook Health Sciences CentreThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- This study is designed as an open-label pilot study
- Masking
- None (open label)
- Enrolment
- 20 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Sunnybrook Health Sciences Centre
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Dr. Peter Giacobbe, Sunnybrook Health Sciences Centre
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04621708
- Sponsor's protocol ID
- 1563
- Status last verified
- Mar 2023
- First submitted
- 21 Oct 2020
- Last updated
- 15 Mar 2023
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Giacobbe P, Bennett A, Nestor S, Derakhshan D, Hamani C, Lipsman N, Feinstein A. Treating Depression in Multiple Sclerosis with Transcranial Magnetic Stimulation: A Pilot Study. Can J Neurol Sci. 2026 Nov 5:1-6. doi: 10.1017/cjn.2026.10715. Online ahead of print.
PubMed 42985745
Study at a glance
From the registry record, last updated by the sponsor on 15 Mar 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pilot Study of the Safety and Tolerability of Left Dorsolateral Prefrontal Cortex Intermittent Theta Burst rTMS for Major Depressive Disorder in Multiple Sclerosis
- ClinicalTrials.gov ID
- NCT04621708
- Acronym / sponsor ID
- 1563
- Conditions
- Multiple Sclerosis, Major Depressive Disorder
- Keywords
- MS, MDD
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 20 participants (estimated)
- Lead sponsor
- Sunnybrook Health Sciences CentreUniversity, hospital or other
- Study start
- 30 Apr 2020 (actual)
- Primary completion
- 30 Apr 2024 (estimated)
- Study completion
- 30 Apr 2024 (estimated)
- First posted
- 9 Nov 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The main purpose of this study is to investigate the safety and tolerability of intermittent Theta Burst (iTBS) repetitive transcranial magnetic stimulation (rTMS), its effectiveness in alleviating depressive symptoms as well as its effects on cognition. Although iTBS rTMS is approved for use, there have been no safety and tolerability evaluations of this form of rTMS in Multiple Sclerosis (MS).
Detailed description
The main purpose of this study is to investigate the safety and tolerability of intermittent Theta Burst (iTBS), its effectiveness in alleviating depressive symptoms, concomitant neuropsychiatric symptoms such as anxiety and fatigue in people with MS, as well as its effects on cognition. Although iTBS repetitive transcranial magnetic stimulation (rTMS) is approved for use in major depressive disorder (MDD), there have been no safety and tolerability evaluations of this form of rTMS in Multiple Sclerosis (MS) patient with MDD. Although iTBS rTMS has previously been found safe and effective for treating spasticity in people with MS, this will be the first study to investigate the safety and tolerability of Left Dorsolateral Prefrontal Cortex (L-DLPFC) iTBS rTMS for MDD in MS
This study is designed as an open-label pilot study. Participants will undergo baseline evaluations to confirm a diagnosis of MDD and to assess your eligibility for rTMS treatment. If deemed eligible, participants will receive iTBS treatment. iTBS is a form of rTMS approved by Health Canada for treatment of MDD. iTBS rTMS treatment involves 3 minutes of non-invasive brain stimulation, 5 days a week, for 4 weeks, for a total of 20 treatments. While receiving iTBS rTMS, participants will be seen daily by the rTMS operator who is a mental health nurse. While receiving iTBS rTMS, participants will see the research coordinator and study psychiatrist on a weekly basis, to complete clinical assessments to evaluate their neuropsychiatric symptoms and assess any side effects from the rTMS procedure. As part of the suggested pathophysiological profile of depression the levels of inflammatory cytokines tumor necrosis factor ⍺ (TNF-⍺) and interleukin-6 (IL-6) have shown elevated concentration levels in plasma of depressed compared to non-depressed individuals. In this study, we aim to investigate the levels of these inflammatory cytokine markers and their change with iTBS.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- This study is designed as an open-label pilot study
| Arm | Type | Receives |
|---|---|---|
| Left DLPFC iTBS rTMS | Experimental | Device: Repetitive transcranial magnetic stimulation |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Men and women ≥18 and ≤70 years of age, inclusive.
- History of MS confirmed by a neurologist.
- Patients who are able and willing to give consent and able to adhere to treatment schedule and attend study visits, as determined by study psychiatrist
- DSM-V diagnosis of Major Depressive Disorder (MDD)
- Moderate severity with a Hamilton Depression Rating Scale (HAMD) at least 16
Key exclusion criteria (16 listed)
- Active substance abuse or dependence in the last three months, except nicotine
- Active suicidal intent
- Currently pregnant (as determined by history and serum HCG) or lactating.
- A diagnosis of Bipolar Disorder
- A history of past or current psychotic symptoms
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Repetitive transcranial magnetic stimulationLeft DLPFC iTBS rTMS | Device | Left DLPFC iTBS rTMS |
Primary outcome
Change in depressive symptoms
Time frame: Baseline and 4 weeks post-treatment
The primary outcome measure will be the reduction in depressive symptoms as measured by the Hamilton Depression Rating Scale-17 at the end of the 4-week trial of iTBS rTMS. This will be measured as both a continuous variable (score on HAMD-17 at week 4 - score on HAMD-17 at week 0 pre-treatment) and a categorical one (i.e. the response rates of >50% reduction from baseline HAMD-17 and remission rates defined as HAMD-17 <7).
5 secondary outcomes
Change in anxiety and depressive symptoms
Time frame: Baseline and 4 weeks post-treatment
Change in fatigue, severity and impact
Time frame: Baseline and 4 weeks post-treatment
Change in Neuropsychological function
Time frame: Baseline and 4 weeks post-treatment
Change in fatigue, severity and impact
Time frame: Baseline and 4 weeks post-treatment
Change in Neuropsychological function
Time frame: Baseline and 4 weeks post-treatment
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Mar 2023.
- Derived from this study: PubMed 42985745Giacobbe P, Bennett A, Nestor S, Derakhshan D, Hamani C, Lipsman N, Feinstein A. Treating Depression in Multiple Sclerosis with Transcranial Magnetic Stimulation: A Pilot Study. Can J Neurol Sci. 2026 Nov 5:1-6. doi: 10.1017/cjn.2026.10715. Online ahead of print.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Repetitive transcranial magnetic stimulation in people with Multiple Sclerosis and Major Depressive Disorder, run by Sunnybrook Health Sciences Centre at 1 site in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 15 Mar 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Anusha Baskaran, PhD (416-480-6100 ext. 1650, anusha.baskaran@sunnybrook.ca), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in depressive symptoms (time frame: Baseline and 4 weeks post-treatment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04621708, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Mar 2023.