Investigating Predictors of Treatment Response in Treatment-Resistant Depression (TRD) With Interleaved TMS/fMRI

NCT03642522 | Completed

• 1 other identifier: H14-02819
• Study Type: interventional
• Target: 72
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this trial is identify biomarkers of response to repetitive transcranial magnetic stimulation (rTMS) in individuals with first episode or treatment resistant depression. These biomarkers include simultaneous TMS-fMRI (functional magnetic resonance imaging), a blood smear, cognitive and behavioural assessments, questionnaires, and neurophysiology.

Conditions

Major Depressive Disorder; Depression

Keywords

repetitive transcranial magnetic stimulation; rTMS; neurostimulation; biomarker; treatment-resistant

Outcome Measures

Primary Outcomes (1)

• Inventory of Depressive Symptomatology (IDS-30)

  The inventory of depressive symptomatology is a clinician-rated depression scale. Outcome will be total score. Minimum score is 0 and maximum score is 84. Higher scores indicate worse severity.

  4 weeks

Secondary Outcomes (1)

• Quick Inventory of Depressive Symptomatology (QIDS-SR)

  4 weeks

Other Outcomes (4)

• Quick Inventory of Depressive Symptomatology (QIDS-SR)

  16 weeks

• Inventory of Depressive Symptomatology (IDS-30)

  16 weeks

• The Montgomery-Åsberg Depression Rating Scale (MADRS)

  4 weeks

Study Arms (1)

1 Hz rTMS

EXPERIMENTAL

30 minutes of 1 Hz rTMS to the right dorsolateral prefrontal cortex (R\_DLPFC)

Device: repetitive transcranial magnetic stimulation

Interventions

repetitive transcranial magnetic stimulation DEVICE

rTMS is a Health-Canada- and FDA-approved treatment for treatment-resistant depression (TRD), using focused magnetic field pulses to stimulate brain regions involved in emotion regulation, safely and non-invasively. rTMS can be applied at varying discharge frequencies which have differential effects on cortical excitability. At a low frequency (≤ 1Hz), rTMS reduces cortical excitability, while at frequencies greater than 1 Hz, rTMS facilitates cortical excitability3. In MDD, either high- frequency rTMS (HF-rTMS) applied over the left dorsolateral prefrontal cortex (DLPFC) or low- frequency rTMS (LF-rTMS) applied over the right DLPFC have similar efficacy. This study utilizes low frequency rTMS to the right DLPFC.

Also known as: rTMS

1 Hz rTMS

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients will be included if they:
• are outpatients
• are voluntary and competent to consent to treatment
• have a Mini-International Neuropsychiatric Interview (MINI) confirmed diagnosis of MDD, single or recurrent
• are between the ages of 18 and 80 years
• have failed to achieve a clinical response to at least one adequate dose of an antidepressant based on an Antidepressant Treatment History Form (ATHF) score of score ≥ 3 in the current episode OR have been unable to tolerate at least 2 separate trials of antidepressants of inadequate dose and duration (ATHF 1 or 2)
• have a score ≥ 22 on the IDS item
• have had no increase or initiation of any psychotropic medication in the 4 weeks prior to initiation of rTMS
• able to adhere to the treatment schedule
• pass the TMS adult safety screening (TASS) questionnaire
• Patients will be included if they:
• are outpatients
• are voluntary and competent to consent to treatment
• have a Mini-International Neuropsychiatric Interview (MINI) confirmed diagnosis of MDD, single or recurrent
• are between the ages of 18 and 80 years

You may not qualify if:

• Patients are excluded if they:
• have a history of substance dependence or abuse within the last 3 months
• have a concomitant major unstable medical illness, cardiac pacemaker or implanted medication pump
• have active suicidal intent
• are pregnant
• have a lifetime Mini-International Neuropsychiatric Interview (MINI) diagnosis of bipolar I or II disorder, schizophrenia, schizoaffective disorder, schizophreniform disorder, delusional disorder, or current psychotic symptoms
• have a MINI diagnosis of obsessive compulsive disorder, post-traumatic stress disorder (current or within the last year), anxiety disorder (generalized anxiety disorder, social anxiety disorder, panic disorder), or dysthymia, assessed by a study investigator to be primary and causing greater impairment than MDD
• have a diagnosis of any personality disorder, and assessed by a study investigator to be primary and causing greater impairment than MDD
• have failed a course of ECT in the current episode or previous episode
• have received rTMS for any previous indication due to the potential compromise of expectancy effects
• have any significant neurological disorder or insult including, but not limited to: any condition likely to be associated with increased intracranial pressure, space occupying brain lesion, any history of seizure except those therapeutically induced by ECT, cerebral aneurysm, Parkinson's disease, Huntington's chorea, multiple sclerosis, significant head trauma with loss of consciousness for greater than 5 minutes
• have an intracranial implant (e.g., aneurysm clips, shunts, stimulators, cochlear implants, or electrodes) or any other metal object within or near the head, excluding the mouth, that cannot be safely removed
• 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
• have a clinically significant laboratory abnormality, in the opinion of the one of the principal investigators
• are currently (or in the last 4 weeks) taking lorazepam greater than 2 mg daily (or equivalent) or any dose of an anticonvulsant, due to the potential to limit rTMS efficacy

Sponsors & Collaborators

• University of British Columbia: lead
• University of Victoria: collaborator

Study Sites (1)

Non-Invasive Neurostimulation Therapies lab, University of British Columbia

Vancouver, British Columbia, V6T2A1, Canada

Location

Related Publications (1)

• Ge R, Humaira A, Gregory E, Alamian G, MacMillan EL, Barlow L, Todd R, Nestor S, Frangou S, Vila-Rodriguez F. Predictive Value of Acute Neuroplastic Response to rTMS in Treatment Outcome in Depression: A Concurrent TMS-fMRI Trial. Am J Psychiatry. 2022 Jul;179(7):500-508. doi: 10.1176/appi.ajp.21050541. Epub 2022 May 18.

  PMID: 35582784 DERIVED

MeSH Terms

Conditions

Depressive Disorder, Major; Depression

Interventions

Transcranial Magnetic Stimulation

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders; Behavioral Symptoms; Behavior

Intervention Hierarchy (Ancestors)

Magnetic Field Therapy; Therapeutics

Study Officials

• Fidel Vila-Rodriguez, MD

  University of British Columbia

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: August 9, 2018
• First Posted: August 22, 2018
• Study Start: November 1, 2018
• Primary Completion: March 30, 2020
• Study Completion: August 1, 2020
• Last Updated: January 12, 2021

Record last verified: 2021-01

Locations

CA (1)