iTBS Study for Depression in Patients With Multiple Sclerosis
Primary Purpose
Multiple Sclerosis, Depression, Anxiety
Status
Unknown status
Phase
Not Applicable
Locations
Study Type
Interventional
Intervention
intermittent theta burst stimulation using a MagPro X100
sham intermittent theta burst stimulation using a MagPro X100
Sponsored by
About this trial
This is an interventional treatment trial for Multiple Sclerosis focused on measuring Multiple Sclerosis, Depression, Transcranial Magnetic Stimulation
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
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Sham Comparator
Arm Label
iTBS stimulation
sham iTBS stimulation
Arm Description
iTBS stimulation to left dorsolateral prefrontal cortex (DLPFC), twice daily, 10 days
sham iTBS stimulation to left dorsolateral prefrontal cortex (DLPFC), twice daily, 10 days
Outcomes
Primary Outcome Measures
Change in Montgomery-Asberg Depression Rating Scale (MADRS)
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
Presence and changes in severity of side effects
Adverse events will be assessed by the physician from Department of Neurology weekly.
Change in Beck Depressive Inventory (BDI)
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)
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 Fatigue Severity Scale (FSS)
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 Pittsburgh Sleep Quality Index (PSQI)
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 Expand Disability Status Scale (EDSS)
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.
Change in Cortical silent period (CSP) duration
CSP duration will be measured by Magventure X100 + option.
Change in short-interval intracortical inhibition (SICI)
SICI will be measured by Magventure X100 + option.
Change in intracortical facilitation (ICF)
ICF will be measured by Magventure X100 + option.
Changes in long-interval intracortical inhibition (LICI)
LICI will be measured by Magventure X100 + option.
Change in slow-wave/fast-wave (theta/beta) ratio from resting-state electroencephalograph (EEG) recording
Resting-state EEG will be recorded by Nicolet EEG system.
Serum biomarker
Serum biomarker such as BDNF, TNF-alpha, IL-1 beta, S100 beta will be examined before and after TMS treatment.
Full Information
NCT ID
NCT04524039
First Posted
August 2, 2020
Last Updated
November 21, 2020
Sponsor
Third Affiliated Hospital, Sun Yat-Sen University
1. Study Identification
Unique Protocol Identification Number
NCT04524039
Brief Title
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
2. Study Status
Record Verification Date
November 2020
Overall Recruitment Status
Unknown status
Study Start Date
December 1, 2020 (Anticipated)
Primary Completion Date
September 1, 2022 (Anticipated)
Study Completion Date
December 31, 2022 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Third Affiliated Hospital, Sun Yat-Sen University
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Multiple Sclerosis, Depression, Anxiety
Keywords
Multiple Sclerosis, Depression, Transcranial Magnetic Stimulation
7. Study Design
Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
ParticipantOutcomes Assessor
Allocation
Randomized
Enrollment
30 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
iTBS stimulation
Arm Type
Experimental
Arm Description
iTBS stimulation to left dorsolateral prefrontal cortex (DLPFC), twice daily, 10 days
Arm Title
sham iTBS stimulation
Arm Type
Sham Comparator
Arm Description
sham iTBS stimulation to left dorsolateral prefrontal cortex (DLPFC), twice daily, 10 days
Intervention Type
Device
Intervention Name(s)
intermittent theta burst stimulation using a MagPro X100
Intervention Description
Patients randomized to receive iTBS in left dorsolateral prefrontal cortex, each treatment will consist of 600 stimuli (triplet 50 Hz bursts, repeated at 5 Hz; 2 s on and 8 s off; total duration of 3 min 12 s). Simulated iTBS will be administered using Magventure static cooling MCF-B65 coil.
Intervention Type
Device
Intervention Name(s)
sham intermittent theta burst stimulation using a MagPro X100
Intervention Description
Patients randomized to receive sham iTBS will undergo the same procedure to patients receiving real iTBS. Sham iTBS will be administered using Magventure static cooling MCF-P-B65 coil that shares the same mechanical outline and produces identical sound level to MCF-B65 coil without stimulating the cerebral cortex.
Primary Outcome Measure Information:
Title
Change in Montgomery-Asberg Depression Rating Scale (MADRS)
Description
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.
Time Frame
0 (baseline), 10 days and 4 weeks
Secondary Outcome Measure Information:
Title
Presence and changes in severity of side effects
Description
Adverse events will be assessed by the physician from Department of Neurology weekly.
Time Frame
0 (baseline), 10 days and 4 weeks
Title
Change in Beck Depressive Inventory (BDI)
Description
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.
Time Frame
0 (baseline), 10 days and 4 weeks
Title
Change in 21-item Beck's Anxiety Inventory (BAI)
Description
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.
Time Frame
0 (baseline), 10 days and 4 weeks
Title
Change in Fatigue Severity Scale (FSS)
Description
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.
Time Frame
0 (baseline), 10 days and 4 weeks
Title
Change in Pittsburgh Sleep Quality Index (PSQI)
Description
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.
Time Frame
0 (baseline), 10 days and 4 weeks
Title
Change in Expand Disability Status Scale (EDSS)
Description
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.
Time Frame
0 (baseline), 10 days and 4 weeks
Title
Change in Cortical silent period (CSP) duration
Description
CSP duration will be measured by Magventure X100 + option.
Time Frame
0 (baseline), 10 days and 4 weeks
Title
Change in short-interval intracortical inhibition (SICI)
Description
SICI will be measured by Magventure X100 + option.
Time Frame
0 (baseline), 10 days and 4 weeks
Title
Change in intracortical facilitation (ICF)
Description
ICF will be measured by Magventure X100 + option.
Time Frame
0 (baseline), 10 days and 4 weeks
Title
Changes in long-interval intracortical inhibition (LICI)
Description
LICI will be measured by Magventure X100 + option.
Time Frame
0 (baseline), 10 days and 4 weeks
Title
Change in slow-wave/fast-wave (theta/beta) ratio from resting-state electroencephalograph (EEG) recording
Description
Resting-state EEG will be recorded by Nicolet EEG system.
Time Frame
0 (baseline), 10 days and 4 weeks
Title
Serum biomarker
Description
Serum biomarker such as BDNF, TNF-alpha, IL-1 beta, S100 beta will be examined before and after TMS treatment.
Time Frame
0 (baseline), 10 days
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Wei Qiu, MD/Ph.D
Phone
+8615899968330
Email
qiuwei120@vip.163.com
First Name & Middle Initial & Last Name or Official Title & Degree
Liqing Wang, MD/Ph.D
Phone
+86(20)85253088
Email
wanglq5@mail.sysu.edu.cn
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Wei Qiu, MD/Ph.D
Organizational Affiliation
Third Affiliated Hospital, Sun Yat-Sen University
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Liqing Wang, MD/Ph.D
Organizational Affiliation
Third Affiliated Hospital, Sun Yat-Sen University
Official's Role
Principal Investigator
12. IPD Sharing Statement
Plan to Share IPD
No
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iTBS Study for Depression in Patients With Multiple Sclerosis
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