Investigation of the Effects of Repetitive Transcranial Magnetic Stimulation on Cognition in Depression

NCT03977038 | Completed FDA Device

• 1 other identifier: 096-2019
• Study Type: observational
• Target: 25
• Locations: 1 country
• Sites: 1

Brief Summary

According to the World Health Organization, MDD is attributed as the leading cause of disability worldwide, leaving 300 million individuals affected. Despite the efficacy of pharmacotherapy, a subset of MDD patients, classified as TRD, exhibit suboptimal response and thus require alternative treatment options such as rTMS. Emotional-laden "hot"and Neutral "cold" cognitions are shown to be dysfunctional in depression. Potential pro-cognitive effects remain inconclusive. In this study the investigators seek to investigate whether visual scanning patterns of emotionally laden images may be a biological marker and predictor of rTMS antidepressant efficacy. If so, then changes in visual scanning patterns are expected to precede clinical symptom improvement. Furthermore, changes in visual scanning patterns (which characterizes the state of hot cognition) are compared simultaneously to changes in cold cognition in order to elucidate the neural mechanisms underlying rTMS-induced changes in cognition. It is hypothesized that participants who are responders to rTMS will exhibit a decrease in the amount of time spent looking at dysphoric images will precede clinically detectable changes in mood as measured by a reduction in the scores on the 17-item Hamilton Depression Rating Scale (HDRS-17). The hypothesis for this study corresponds to the alleviation of the dysfunction within the hot cognitive system as a result of rTMS and a potential compensatory effect of cold cognition as a natural reaction of resetting the allocation of cognitive resources.

Conditions

Major Depressive Disorder; Treatment Resistant Depression

Keywords

Repetitive Transcranial Magnetic Stimulation; Hot Cognition; Cold Cognition; Attentional Imaging; Eye tracking; Cognitive impairment; Cognition

Outcome Measures

Primary Outcomes (2)

• Change in cold cognition

  Also known as neutral or "non-emotional" cognition, it will be measured by the Cambridge Neuropsychological Test Automated Battery (CANTAB) utilized in the domains of attention, executive function, memory and social/emotional cognition

  Participants will be tested once every two weeks for six weeks. To follow up on investigating lasting results, this cognitive battery will be conducted at follow-up at one-month mark (Week 10) from the last visit at Week 6

• Change in hot cognition

  Also known as "emotional" cognition, it will be measured through attentional imaging by an eye tracking task where participants will view image slides presenting images of different valences (emotional, neutral) and the participant's eye gaze estimates will be recorded

  Participants will be tested once every two weeks for six weeks. To follow up on investigating lasting results, visual stimuli test will be conducted at one-month mark (Week 10) from the last visit at Week 6

Secondary Outcomes (2)

• depressive symptoms (physician-rated)

  TRD participants are assessed for their depressive symptom severity in response to rTMS treatment by the study psychiatrist every two weeks for six weeks, followed by a follow-up visit at one-month mark (Week 10).

• depressive symptoms (self-report)

  TRD participants are asked to self-report their depressive symptom severity in response to rTMS treatment every two weeks for six weeks, followed by a follow-up visit at one-month mark (Week 10).

Study Arms (2)

TRD sample

Individuals in the treatment resistant depression (TRD) sample suffer from the condition called TRD. The intervention that will be administered to this group is the standardized rTMS treatment using High Frequency dTMS (HF-dTMS) stimulation over L-DLPFC, at the frequency of 18Hz, at 120% value of the individual's motor threshold, in 5 daily sessions per week, taking place each weekday, over the course of 6 weeks.

Device: repetitive transcranial magnetic stimulation

Healthy Controls (HC) sample

Individuals in the HC sample are age-, sex-, education-matched to the individuals in the TRD sample. HC sample does not receive any therapeutic treatment and are solely examined as a comparative measure of normal cognitive capabilities.

Interventions

repetitive transcranial magnetic stimulation DEVICE

Repetitive transcranial magnetic stimulation (rTMS) is prescribed as first-line treatment for TRD patients (4). rTMS is safe, tolerable and non-invasive neurostimulation procedure where powerful magnetic pulses are transmitted through the skull into the underlying cortical cortex with the aim of electrical current induction within the neural tissue. This study administers a standard dose of rTMS treatment to the TRD patient sample consisting of high frequency deep TMS (HF-dTMS) stimulation over left dorsolateral prefrontal cortex (L-DLPFC), at the frequency of 18Hz, at 120% value of the individual's motor threshold, in 5 daily sessions per week, taking place each weekday, over the course of 6 weeks. The technology of dTMS, which will be used in this study, is an adaptation of the therapeutic intervention of rTMS with the advancement of possessing higher efficacy in targeting deeper brain regions of interest.

TRD sample

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Potential TRD participants in this study will be individuals referred by their family doctor or community psychiatrist for diagnostic clarification and/or the provision of treatment options for their mood symptoms. Additionally, individuals who respond to the study advertisement and based on the telephone screening performed by the study physicians, are deemed to meet the study's inclusion and exclusion criteria will be the provision of treatment options for their mood symptoms as well as the opportunity to participate in this study. Healthy Control participants will be age-,sex- and education- matched to the TRD participants and will be representative of the community sample, consisting of healthy individuals with no psychiatric illness.

You may qualify if:

• For the patient group, subjects are required to meet DSM-5 criteria for a diagnosis of Major Depressive Disorder.
• For the healthy control group, subjects should be matched to the patient group in domains of age, sex and education; as well as being devoid of any current or previous history of neuropsychiatric illness.
• Patient group subjects must have a score of at least 20 on the HDRS-17 at time of assessment.
• All subjects (patients and healthy controls) should be between the ages of 18 and 65.
• All subjects (patients and healthy controls) must be capable of providing their informed written consent.
• For the patient group, it is essential that subjects who are taking antidepressant medications maintain a stable dose of medication for at least 4 weeks prior to start of treatment and also continue maintaining this stability throughout the course of treatment.

You may not qualify if:

• Subjects suffering from unstable medical conditions
• Subjects with current and past history of epilepsy
• Recent history of substance abuse/dependence (excluding nicotine and caffeine) within the past 6 months as defined by DSM-5
• History of suicide attempts or self-harm within the past 12 months
• Current or previous diagnosis of Bipolar Disorder, Schizophrenia or other psychotic disorders (including psychotic disorder due to general medical condition, substance-induced psychotic, psychotic disorder not otherwise specified) as defined by the MINI
• Previous lack of response to rTMS
• Electroconvulsive therapy (ECT) within the 3 months prior to beginning of study
• Inability to communicate in English language

Sponsors & Collaborators

• Sunnybrook Health Sciences Centre: lead

Study Sites (1)

Sunnybrook Health Sciences Centre

Toronto, Ontario, M4N 3M5, Canada

Location

Related Publications (20)

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• World Health Organization. Depression: Fact Sheet. World Health Organization website. http://www.who.int/mediacentre/factsheets/fs369/en/. Updated February 2017.

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• Gupta M, Holshausen K, Best MW, Jokic R, Milev R, Bernard T, Gou L, Bowie CR. Relationships among neurocognition, symptoms, and functioning in treatment-resistant depression. Arch Clin Neuropsychol. 2013 May;28(3):272-81. doi: 10.1093/arclin/act002. Epub 2013 Jan 22.

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  PMID: 23481353 BACKGROUND

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  BACKGROUND

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  PMID: 28072659 BACKGROUND

• Berlim MT, Van den Eynde F, Daskalakis ZJ. High-frequency repetitive transcranial magnetic stimulation accelerates and enhances the clinical response to antidepressants in major depression: a meta-analysis of randomized, double-blind, and sham-controlled trials. J Clin Psychiatry. 2013 Feb;74(2):e122-9. doi: 10.4088/JCP.12r07996.

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• Serafini G, Pompili M, Belvederi Murri M, Respino M, Ghio L, Girardi P, Fitzgerald PB, Amore M. The effects of repetitive transcranial magnetic stimulation on cognitive performance in treatment-resistant depression. A systematic review. Neuropsychobiology. 2015;71(3):125-39. doi: 10.1159/000381351. Epub 2015 Apr 25.

  PMID: 25925699 BACKGROUND

• Cambridge Neuropsychological Test Automated Battery (CANTAB). Cambridge Cognition Ltd Website. https://www.cambridgecognition.com/cantab/

  BACKGROUND

• Dowlati Y, Herrmann N, Swardfager W, Liu H, Sham L, Reim EK, Lanctot KL. A meta-analysis of cytokines in major depression. Biol Psychiatry. 2010 Mar 1;67(5):446-57. doi: 10.1016/j.biopsych.2009.09.033. Epub 2009 Dec 16.

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• Howren MB, Lamkin DM, Suls J. Associations of depression with C-reactive protein, IL-1, and IL-6: a meta-analysis. Psychosom Med. 2009 Feb;71(2):171-86. doi: 10.1097/PSY.0b013e3181907c1b. Epub 2009 Feb 2.

  PMID: 19188531 BACKGROUND

• Strawbridge R, Arnone D, Danese A, Papadopoulos A, Herane Vives A, Cleare AJ. Inflammation and clinical response to treatment in depression: A meta-analysis. Eur Neuropsychopharmacol. 2015 Oct;25(10):1532-43. doi: 10.1016/j.euroneuro.2015.06.007. Epub 2015 Jun 20.

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• Daniele A, Divella R, Paradiso A, Mattioli V, Romito F, Giotta F, Casamassima P, Quaranta M. Serotonin transporter polymorphism in major depressive disorder (MDD), psychiatric disorders, and in MDD in response to stressful life events: causes and treatment with antidepressant. In Vivo. 2011 Nov-Dec;25(6):895-901.

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• Lee BH, Kim YK. The roles of BDNF in the pathophysiology of major depression and in antidepressant treatment. Psychiatry Investig. 2010 Dec;7(4):231-5. doi: 10.4306/pi.2010.7.4.231. Epub 2010 Nov 23.

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  PMID: 25300442 BACKGROUND

Biospecimen

Retention: SAMPLES WITH DNA

Whole blood specimen will be retained from all participants at 4 time points in the study (Week 0 (baseline), Week 2, Week 6 (last visit) and Week 10 (follow-up)). Bloodwork is obtained in order to monitor for genotype of serotonin transporter polymorphism (5-HTTLPR) , BDNF and potential alterations in the present levels of inflammatory markers of TNF-⍺ and IL-6 involved in the pathophysiological inflammation profile of depression.

MeSH Terms

Conditions

Depressive Disorder, Major; Depressive Disorder, Treatment-Resistant; Cognitive Dysfunction

Interventions

Transcranial Magnetic Stimulation

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders; Cognition Disorders; Neurocognitive Disorders

Intervention Hierarchy (Ancestors)

Magnetic Field Therapy; Therapeutics

Study Officials

• Peter Giacobbe, MD, FRCPC

  Harquail Centre For Neuromodulation, Sunnybrook Health Sciences Centre

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Target Duration: 1 Month
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Clinical Head, Harquail Centre for Neuromodulation

Study Record Dates

• First Submitted: May 23, 2019
• First Posted: June 6, 2019
• Study Start: May 30, 2020
• Primary Completion: June 6, 2022
• Study Completion: June 6, 2022
• Last Updated: March 15, 2023

Record last verified: 2023-03

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)