iTBS Study for Depression in Patients With Multiple Sclerosis

Not Applicable

• Conditions: Depression, Anxiety; Multiple Sclerosis
• Interventions: Device: sham intermittent theta burst stimulation using a MagPro X100; Device: intermittent theta burst stimulation using a MagPro X100

• Registration Number: NCT04524039
• Lead Sponsor: Third Affiliated Hospital, Sun Yat-Sen University

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.

Study Timeline

• Study First Submitted: 2020-08-02
• Study First Submitted QC: 2020-08-19
• Study First Posted: 2020-08-24
• Status Verified: 2020-11
• Last Update Submitted: 2020-11-21
• Last Update Posted: 2020-11-24
• Study Start: 2020-12-01
• Primary Completion: 2022-09-01
• Study Completion: 2022-12-31

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 30

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
sham iTBS stimulation	sham intermittent theta burst stimulation using a MagPro X100	sham iTBS stimulation to left dorsolateral prefrontal cortex (DLPFC), twice daily, 10 days
iTBS stimulation	intermittent theta burst stimulation using a MagPro X100	iTBS stimulation to left dorsolateral prefrontal cortex (DLPFC), twice daily, 10 days

Primary Outcome Measures

Name	Time	Method
Change in Montgomery-Asberg Depression Rating Scale (MADRS)	0 (baseline), 10 days and 4 weeks	The MADRS is a 0-60 point scale to measure depression severity with a higher number indicating more severe depression. A score of 0-6 indicates symptoms absent, 7-19 indicates mild depression, 20-34 moderate, and \> 34 severe.

Secondary Outcome Measures

Name	Time	Method
Change in Fatigue Severity Scale (FSS)	0 (baseline), 10 days and 4 weeks	The FSS is a 9-item scale which measure the severity of fatigue and its effect on an individual's daily living and social participation. The total score ranges from 9 to 63, with a higher score indicate greater fatigue severity.
Change in Cortical silent period (CSP) duration	0 (baseline), 10 days and 4 weeks	CSP duration will be measured by Magventure X100 + option.
Change in short-interval intracortical inhibition (SICI)	0 (baseline), 10 days and 4 weeks	SICI will be measured by Magventure X100 + option.
Change in Beck Depressive Inventory (BDI)	0 (baseline), 10 days and 4 weeks	BDI is a widely utilized to assess depression in MS patients. It is a 21-item self-reporting questionnaire for evaluating the severity of depression. The score range is 0-63 with higher scores indicating higher intensity.
Change in 21-item Beck's Anxiety Inventory (BAI)	0 (baseline), 10 days and 4 weeks	BAI is a self-report test for measuring anxiety severity and level. It contains 21 multiple-choice questions. The score range is 0-63 with higher scores indicating higher intensity.
Change in Expand Disability Status Scale (EDSS)	0 (baseline), 10 days and 4 weeks	EDSS is a standardized method used to classify the severity and progression of multiple sclerosis. It provides a total score on a scale that ranges from 0 to 10.
Presence and changes in severity of side effects	0 (baseline), 10 days and 4 weeks	Adverse events will be assessed by the physician from Department of Neurology weekly.
Change in Pittsburgh Sleep Quality Index (PSQI)	0 (baseline), 10 days and 4 weeks	PSQI is a self-rated questionnaire designed to evaluate overall sleep quality during the past month. Each of the questionnaire's 19 self-reported items belongs to one of seven subcategories: sleep quality, sleep latency, sleep duration, sleep efficiency, sleep disturbance, use of sleep medication, degree of daytime dysfunction.
Change in intracortical facilitation (ICF)	0 (baseline), 10 days and 4 weeks	ICF will be measured by Magventure X100 + option.
Changes in long-interval intracortical inhibition (LICI)	0 (baseline), 10 days and 4 weeks	LICI will be measured by Magventure X100 + option.
Change in slow-wave/fast-wave (theta/beta) ratio from resting-state electroencephalograph (EEG) recording	0 (baseline), 10 days and 4 weeks	Resting-state EEG will be recorded by Nicolet EEG system.
Serum biomarker	0 (baseline), 10 days	Serum biomarker such as BDNF, TNF-alpha, IL-1 beta, S100 beta will be examined before and after TMS treatment.