Clinical trial NCT04524039: iTBS Study for Depression in Patients With Multiple Sclerosis
Official title: Intermittent Theta Burst Stimulation (iTBS) for the Treatment of Depression in Patients With Multiple Sclerosis: a Randomized Controlled Study
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Multiple Sclerosis
Depression, Anxiety
Keywords: Multiple Sclerosis
Depression
Transcranial Magnetic Stimulation
Lead sponsor: Third Affiliated Hospital, Sun Yat-Sen University
Sponsor class: OTHER
First posted: 2020-08-24
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Multiple sclerosis (MS) is a chronic and demyelinating disease of the central nervous system. It is one of the most common cause of neurological disability in young adults. Depression is a common symptom in MS patients, with lifetime prevalence rates going up to 50%. Depression not only reduces the response to treatment, delays the recovery of neurological function and social ability, but also significantly increases the risk of disability in patients with MS.

Transcranial magnetic stimulation (TMS) is a non-invasive method of brain stimulation that is based on electromagnetic induction. Intermittent theta burst stimulation (TBS), a newer form of rTMS, delivers 600 pulses in just 3 min, versus 37.5 min for conventional rTMS, but it has been shown to produce similar effects in patient with treatment-resistant depression.

To observe the effect and safety of iTBS on patients with MS and depression, we design a double-blind, randomized controlled study. Results of this research will inform on the efficiency of the TMS for the treatment of depression in MS patients, which will reduce the risk of disability and improve the quality of life.

Detailed description: Multiple sclerosis (MS) is a chronic and demyelinating disease of the central nervous system. It is one of the most common cause of neurological disability in young adults. Depression is a common symptom in MS patients, with lifetime prevalence rates going up to 50%. Depression not only reduces the response to treatment, delays the recovery of neurological function and social ability, but also significantly increases the risk of disability in patients with MS. It is worth noting that depression remains widely underdiagnosed and untreated in MS patients. The investigators aim to treat the depression in MS patients using a non-invasive method, which will help improve life quality and reduce the risk of disability in patients.

Transcranial magnetic stimulation (TMS) is a non-invasive method of brain stimulation that uses magnetic fields to stimulate nerve cells in brain. Repetitive TMS (rTMS) is usually applied in antidepressant-resistant depression. Furthermore, some clinical trials show that rTMS also significantly improve Parkinson's related depression and postpartum depression. Intermittent theta burst stimulation (TBS), a newer form of rTMS, delivers 600 pulses in just 3 min, versus 37.5 min for conventional rTMS, but it has been shown to produce similar effects in patient with treatment-resistant depression.

In this study, thirty patients who meet the criteria will be included. They will then be randomly assigned into the SHAM or iTBS group for the study intervention. Patients and outcome assessors will be masked to treatment allocation. SHAM or iTBS will be delivered to stimulate left dorsalateral prefrontal cortex (DLPFC). The protocol includes 600 pulses per session: triplet 50 Hz bursts, repeated at 5 Hz; 2 s on and 8 s off. Each patient will receive 2 sessions per day over a period of 10 days (total of 20 sessions). After the treatment phase, patients will be followed up once after two weeks. The presence and severity of side effects will be assessed by the physician from the Department of Neurology. Before and after the iTBS or SHAM intervention and after two weeks of follow-up, primary and secondary measurements will be performed.

Results of this study will inform on the efficiency of the TMS for the treatment of depression in MS patients, which will reduce the risk of disability and improve the quality of life.

Eligibility criteria: Inclusion Criteria:

* 1) Age 18 to 65
* 2) Male and female patients with clinically definite MS according to 2017 McDonald criteria
* 3) EDSS 0 to 6
* 4) Score between 11 and 30 on the Montgomery-Asberg Depression Rating Scale (MADRS) and stable antidepressants therapy \> 1 months before enrollment and during the follow-up period
* 5) Informed consent of patients

Exclusion Criteria:

* 1) History of seizures (personal or family)
* 2) Comedication with neuroleptics or tricyclic antidepressants
* 3) bipolar disorder
* 4) Presence of other diseases of the nervous system (history of stroke, brain injury, brain tumor, increased intracranial pressure)
* 5) Significant neurologic, psychiatric, cardiovascular, hepatic, renal, gastrointestinal, metabolic, or other systemic comorbidities.
* 6) History of drug or alcohol abuse
* 7) Cardiac pacemakers
* 8) Metal implants in the head
* 9) Pregnancy

Primary outcomes:
measure: Change in Montgomery-Asberg Depression Rating Scale (MADRS)
timeFrame: 0 (baseline), 10 days and 4 weeks
Secondary outcomes:
measure: Presence and changes in severity of side effects
timeFrame: 0 (baseline), 10 days and 4 weeks
measure: Change in Beck Depressive Inventory (BDI)
timeFrame: 0 (baseline), 10 days and 4 weeks
measure: Change in 21-item Beck's Anxiety Inventory (BAI)
timeFrame: 0 (baseline), 10 days and 4 weeks
measure: Change in Fatigue Severity Scale (FSS)
timeFrame: 0 (baseline), 10 days and 4 weeks
measure: Change in Pittsburgh Sleep Quality Index (PSQI)
timeFrame: 0 (baseline), 10 days and 4 weeks
measure: Change in Expand Disability Status Scale (EDSS)
timeFrame: 0 (baseline), 10 days and 4 weeks
measure: Change in Cortical silent period (CSP) duration
timeFrame: 0 (baseline), 10 days and 4 weeks
measure: Change in short-interval intracortical inhibition (SICI)
timeFrame: 0 (baseline), 10 days and 4 weeks
measure: Change in intracortical facilitation (ICF)
timeFrame: 0 (baseline), 10 days and 4 weeks
measure: Changes in long-interval intracortical inhibition (LICI)
timeFrame: 0 (baseline), 10 days and 4 weeks
measure: Change in slow-wave/fast-wave (theta/beta) ratio from resting-state electroencephalograph (EEG) recording
timeFrame: 0 (baseline), 10 days and 4 weeks
measure: Serum biomarker
timeFrame: 0 (baseline), 10 days
Other outcomes:
Locations:
Study officials:
affiliation: Third Affiliated Hospital, Sun Yat-Sen University
name: Wei Qiu, MD/Ph.D
role: PRINCIPAL_INVESTIGATOR
affiliation: Third Affiliated Hospital, Sun Yat-Sen University
name: Liqing Wang, MD/Ph.D
role: PRINCIPAL_INVESTIGATOR
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