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

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ClinicalTrials.gov Identifier: NCT03977038
Recruitment Status : Recruiting
First Posted : June 6, 2019
Last Update Posted : July 25, 2019
Sponsor:
Information provided by (Responsible Party):
Dr. Peter Giacobbe, Sunnybrook Health Sciences Centre

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.

Condition or disease Intervention/treatment
Major Depressive Disorder Treatment Resistant Depression Device: repetitive transcranial magnetic stimulation

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Study Type : Observational [Patient Registry]
Estimated Enrollment : 40 participants
Observational Model: Case-Control
Time Perspective: Prospective
Target Follow-Up Duration: 1 Month
Official Title: Investigation of Effects of Repetitive Transcranial Magnetic Stimulation (rTMS) on "Hot" and "Cold" Cognitive Systems In Treatment Resistant Depression (TRD)
Estimated Study Start Date : July 2019
Estimated Primary Completion Date : April 2020
Estimated Study Completion Date : May 2020

Resource links provided by the National Library of Medicine


Group/Cohort Intervention/treatment
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
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.

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.



Primary Outcome Measures :
  1. Change in cold cognition [ Time Frame: 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 ]
    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

  2. Change in hot cognition [ Time Frame: 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 ]
    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


Secondary Outcome Measures :
  1. depressive symptoms (physician-rated) [ Time Frame: 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). ]
    To assess depressive symptom severity in TRD participants, Hamilton Depression Rating Scale (HDRS-17) will be used. HDRS-17 is a 17-item scale, with some items ranging from a score of 0 to 2 points, and some 0 to 4 points. Higher scores represent worse outcome. Total score ranges include: 0-7 considered as "normal", 8-16 categorized as "mild depression", 17-23 as "moderate depression" and above 24 as "severe depression". Minimum score on the scale is 0 and the maximum score on the scale is 52.

  2. depressive symptoms (self-report) [ Time Frame: 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). ]
    To assess depressive symptom severity in TRD participants, Quick Inventory of Depressive Symptomology (QIDS-SR16) will be used. QIDS-SR16 is a 16-item scale, with each item ranging from score of 0 to 3 points. Higher scores represent worse outcome. Total score ranges include: 0-5 considered as "no depression", 6-10 as "mild depression", 11-15 as "moderate depression", 16-20 categorized as "severe depression" and 21-27 as "very severe depression". Minimum score on the scale is 0 and the maximum score is 27.


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.


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
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.
Criteria

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03977038


Contacts
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Contact: Peter Giacobbe, MD, FRCPC 416-480-4085 peter.giacobbe@sunnybrook.ca
Contact: Dorsa Derakhshan, HBSc, MSc Candidate dorsa.derakhshan@mail.utoronto.ca

Locations
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Canada, Ontario
Sunnybrook Health Sciences Centre Recruiting
Toronto, Ontario, Canada, M4N 3M5
Contact: Dorsa Derakhshan, MSc Candidate       dorsa.derakhshan@mail.utoronto.ca   
Principal Investigator: Peter Giacobbe, MD, FRCPC         
Sponsors and Collaborators
Sunnybrook Health Sciences Centre
Investigators
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Principal Investigator: Peter Giacobbe, MD, FRCPC Harquail Centre For Neuromodulation, Sunnybrook Health Sciences Centre
Publications:
World Health Organization. Depression: Fact Sheet. World Health Organization website. http://www.who.int/mediacentre/factsheets/fs369/en/. Updated February 2017.
Robinson OJ, Roiser JP, Sahakian BJ. Hot and cold cognition in depression. In: McIntyre, R.S. (Ed.), Cognitive Impairment in Major Depressive Disorder.Cambridge University Press, Cambridge, UK; 2016.
Cambridge Neuropsychological Test Automated Battery (CANTAB). Cambridge Cognition Ltd Website. https://www.cambridgecognition.com/cantab/

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Responsible Party: Dr. Peter Giacobbe, Clinical Head, Harquail Centre for Neuromodulation, Sunnybrook Health Sciences Centre
ClinicalTrials.gov Identifier: NCT03977038    
Other Study ID Numbers: 096-2019
First Posted: June 6, 2019    Key Record Dates
Last Update Posted: July 25, 2019
Last Verified: July 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: Due to confidentiality, IPD will not be shared with other researchers

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: Yes
Product Manufactured in and Exported from the U.S.: No
Keywords provided by Dr. Peter Giacobbe, Sunnybrook Health Sciences Centre:
Repetitive Transcranial Magnetic Stimulation
Hot Cognition
Cold Cognition
Attentional Imaging
Eye tracking
Cognitive impairment
Cognition
Additional relevant MeSH terms:
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Depression
Depressive Disorder
Depressive Disorder, Major
Depressive Disorder, Treatment-Resistant
Behavioral Symptoms
Mood Disorders
Mental Disorders