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

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).

Study Overview

• Status: Recruiting
• Conditions: Multiple Sclerosis; Major Depressive Disorder
• Intervention / Treatment: Device: Repetitive transcranial magnetic stimulation

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 Type: Interventional
• Enrollment (Anticipated): 20
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Anusha Baskaran, PhD; Phone Number: 1650 416-480-6100; Email: anusha.baskaran@sunnybrook.ca

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M4N 3M5
      • Recruiting
      • Sunnybrook Health Sciences Centre
      • Contact: Anusha Baskarna, PhD; Phone Number: 1650 416-480-6100; Email: anusha.baskaran@sunnybrook.ca

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion criteria

1. Men and women ≥18 and ≤70 years of age, inclusive.
2. History of MS confirmed by a neurologist.
3. 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
4. DSM-V diagnosis of Major Depressive Disorder (MDD)
5. Moderate severity with a Hamilton Depression Rating Scale (HAMD) at least 16
6. Patients have had no increase or initiation of any psychotropic medication in the 4 weeks prior to screening
7. Pass the TMS safety screening questionnaire
8. Women of childbearing potential must agree to use a barrier contraception method throughout the study.

Exclusion criteria

1. Active substance abuse or dependence in the last three months, except nicotine
2. Active suicidal intent
3. Currently pregnant (as determined by history and serum HCG) or lactating.
4. A diagnosis of Bipolar Disorder
5. A history of past or current psychotic symptoms
6. 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
7. Having failed a course of ECT in the current episode or previous episode
8. Previous trial of rTMS
9. Personality disorder deemed to be primary pathology
10. 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
11. Clinically significant laboratory abnormality, in the opinion of the investigator
12. Unstable medical illness
13. Contraindication to rTMS, e.g. presence of cardiac pacemaker, intracranial implant, or metal in the cranium
14. Currently on more than 2 mg of lorazepam or equivalent
15. History of seizures, or currently on anticonvulsant for seizures
16. Concurrent use of a medication that may lower the seizure threshold, in the opinion of the investigator e.g. stimulant.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Left DLPFC iTBS rTMS	Device: Repetitive transcranial magnetic stimulation; Left DLPFC iTBS rTMS

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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).	Baseline and 4 weeks post-treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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)	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	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	Baseline and 4 weeks post-treatment
Change in Neuropsychological function	Change in Neuropsychological function, measured objectively by the computerized CANTAB neuropsychological tasks	Baseline and 4 weeks post-treatment

Collaborators and Investigators

• Sponsor: Sunnybrook Health Sciences Centre

Study record dates

Study Major Dates

• Study Start (Actual): April 30, 2020
• Primary Completion (Anticipated): April 30, 2024
• Study Completion (Anticipated): April 30, 2024

Study Registration Dates

• First Submitted: October 21, 2020
• First Submitted That Met QC Criteria: November 3, 2020
• First Posted (Actual): November 9, 2020

Study Record Updates

• Last Update Posted (Actual): March 15, 2023
• Last Update Submitted That Met QC Criteria: March 13, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Keywords: MS; MDD
• Additional Relevant MeSH Terms: Behavioral Symptoms; Mental Disorders; Pathologic Processes; Nervous System Diseases; Mood Disorders; Immune System Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Autoimmune Diseases; Depression; Depressive Disorder; Multiple Sclerosis; Sclerosis; Depressive Disorder, Major
• Other Study ID Numbers: 1563

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No