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Pilot Study of the Safety and Tolerability of L-DLPFC iTBS rTMS for MDD in MS

Primary Purpose

Multiple Sclerosis, Major Depressive Disorder

Status

Recruiting

Phase

Not Applicable

Locations

Canada

Study Type

Interventional

Intervention

Repetitive transcranial magnetic stimulation

About this trial

This is an interventional treatment trial for Multiple Sclerosis focused on measuring MS, MDD

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion criteria

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.

Exclusion criteria

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
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.

Sites / Locations

Sunnybrook Health Sciences CentreRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Left DLPFC iTBS rTMS

Arm Description

Outcomes

Primary Outcome Measures

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).

Secondary Outcome Measures

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.

Change in fatigue, severity and impact

Change in fatigue, severity and impact, measured by the self-report Fatigue Severity Scale (FSS)

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

Change in fatigue, severity and impact

Change in fatigue, severity and impact, measured by the Modified Fatigue Impact Scale (MFIS), respectively

Change in Neuropsychological function

Change in Neuropsychological function, measured objectively by the computerized CANTAB neuropsychological tasks

Full Information

NCT ID

NCT04621708

First Posted

October 21, 2020

Last Updated

March 13, 2023

Sponsor

Sunnybrook Health Sciences Centre

1. Study Identification

Unique Protocol Identification Number

NCT04621708

Brief Title

Pilot Study of the Safety and Tolerability of L-DLPFC iTBS rTMS for MDD in MS

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

Study Type

Interventional

2. Study Status

Record Verification Date

March 2023

Overall Recruitment Status

Recruiting

Study Start Date

April 30, 2020 (Actual)

Primary Completion Date

April 30, 2024 (Anticipated)

Study Completion Date

April 30, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Sunnybrook Health Sciences Centre

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

5. Study Description

Brief 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. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Multiple Sclerosis, Major Depressive Disorder

Keywords

MS, MDD

7. Study Design

Primary Purpose

Treatment

Study Phase

Not Applicable

Interventional Study Model

Single Group Assignment

Model Description

This study is designed as an open-label pilot study

Masking

None (Open Label)

Allocation

N/A

Enrollment

20 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Left DLPFC iTBS rTMS

Arm Type

Experimental

Intervention Type

Device

Intervention Name(s)

Repetitive transcranial magnetic stimulation

Intervention Description

Left DLPFC iTBS rTMS

Primary Outcome Measure Information:

Title

Change in depressive symptoms

Description

Time Frame

Baseline and 4 weeks post-treatment

Secondary Outcome Measure Information:

Title

Change in anxiety and depressive symptoms

Description

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.

Time Frame

Baseline and 4 weeks post-treatment

Title

Change in fatigue, severity and impact

Description

Change in fatigue, severity and impact, measured by the self-report Fatigue Severity Scale (FSS)

Time Frame

Baseline and 4 weeks post-treatment

Title

Change in Neuropsychological function

Description

Change in Neuropsychological function, measured subjectively through the Perceived Deficits Questionnaire (PDQ-5) and objectively by the SDMT and computerized CANTAB neuropsychological tasks

Time Frame

Baseline and 4 weeks post-treatment

Title

Change in fatigue, severity and impact

Description

Change in fatigue, severity and impact, measured by the Modified Fatigue Impact Scale (MFIS), respectively

Time Frame

Baseline and 4 weeks post-treatment

Title

Change in Neuropsychological function

Description

Change in Neuropsychological function, measured objectively by the computerized CANTAB neuropsychological tasks

Time Frame

Baseline and 4 weeks post-treatment

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

70 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion criteria 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. Exclusion criteria 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 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.

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Anusha Baskaran, PhD

Phone

416-480-6100

Ext

1650

anusha.baskaran@sunnybrook.ca

Facility Information:

Facility Name

Sunnybrook Health Sciences Centre

City

Toronto

State/Province

Ontario

ZIP/Postal Code

M4N 3M5

Country

Canada

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Anusha Baskarna, PhD

Phone

416-480-6100

Ext

1650

anusha.baskaran@sunnybrook.ca

12. IPD Sharing Statement

Learn more about this trial

Pilot Study of the Safety and Tolerability of L-DLPFC iTBS rTMS for MDD in MS

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