Examining the Efficacy of Orbitofrontal Cortex rTMS for Depression (OFC-rTMS)

Efficacy of Orbital Frontal Cortex Repetitive Transcranial Magnetic Stimulation Magnetic Stimulation in the Treatment of Refractory Depression

This trial will compare the efficacy of active inhibitory OFC-rTMS to sham OFC-rTMS in major depression. The trial will include structural and functional MRI, EEG, and behavioral measures obtained before, during, and after treatment.

Study Overview

• Status: Completed
• Conditions: Depression
• Intervention / Treatment: Device: Continuous theta-burst stimulation

• Study Type: Interventional
• Enrollment (Actual): 32
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5T 2S8
      • UHN MRI-Guided rTMS Clinic, Toronto Western Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. are outpatients
2. are voluntary and competent to consent to treatment
3. have a Mini-International Neuropsychiatric Interview (MINI) confirmed diagnosis of major depressive disorder (MDD), single or recurrent
4. are between the ages of 18 and 65
5. have failed to achieve a clinical response to an adequate dose of an antidepressant based on an Antidepressant Treatment History Form (ATHF) score of > 3 in the current
6. have a score > 18 on the HAMD-17
7. have had no increase or initiation of any psychotropic medication in the 4 weeks prior to screening
8. able to adhere to the treatment schedule
9. Pass the TMS adult safety-screening (TASS) questionnaire
10. have normal thyroid functioning based on pre-study blood work.

Exclusion Criteria:

1. have a MINI-International Neuropsychiatric (MINI) confirmed diagnosis of substance dependence or abuse within the last 3 months
2. have a concomitant major unstable medical illness, cardiac pacemaker or implanted medication pump
3. have active suicidal intent
4. are pregnant
5. 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
6. 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
7. have a diagnosis of any personality disorder, and assessed by a study investigator to be primary and causing greater impairment than MDD
8. have failed a course of electroconvulsive therapy (ECT) in the current episode or previous episode
9. 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 or equal to 5 minutes
10. 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
11. 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
12. clinically significant laboratory abnormality, in the opinion of the study investigator
13. currently (or in the last 4 weeks) take more than lorazepam 2 mg daily (or equivalent) or any dose of an anticonvulsant due to the potential to limit rTMS efficacy
14. non-correctable clinically significant sensory impairment (i.e., cannot hear well enough to cooperate with interview).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Sham then Active Stimulation; Sham repetitive transcranial magnetic stimulation (rTMS) to right orbitofrontal cortex, twice daily, 5 days per week for 3 weeks, then active rTMS to right orbitofrontal cortex, twice daily, 5 days per week for 3 weeks	Device: Continuous theta-burst stimulation
Experimental: Active then Sham Stimulation; Active repetitive transcranial magnetic stimulation (rTMS) to right orbitofrontal cortex, twice daily, 5 days per week for 3 weeks, then sham rTMS to right orbitofrontal cortex, twice daily, 5 days per week for 3 weeks	Device: Continuous theta-burst stimulation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
17-Item Hamilton Rating Scale for Depression (HAMD-17)	Outcome measured by a change in HAMD-17 score from baseline to 2 weeks post-treatment. A 50% improvement in the score is considered a response to rTMS. A final score of <8 is categorized as remission.	Baseline, after each week of treatment (i.e. after 5 days of treatment) and at 1, 4, and 12 weeks post-treatment.

Secondary Outcome Measures

Outcome Measure	Time Frame
Beck Depression Inventory-II (BDI-II)	Daily for 6 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Magnetic Resonance Imaging (MRI)	10 min resting-state functional MRI (rs-fMRI) at 3 Tesla (3T)	1 week pre- and 1 week post-treatment
Electroencephalography (EEG)	10 min resting-state and task-based (response inhibition, reward sensitivity) acquisitions	Day 1 (First day of treatment), Day 15, and Day 30 (Final day of treatment)]

Collaborators and Investigators

• Sponsor: University Health Network, Toronto
• Collaborators: Canadian Institutes of Health Research (CIHR)

Study record dates

Study Major Dates

• Study Start: June 1, 2016
• Primary Completion (Actual): July 1, 2017
• Study Completion (Actual): July 1, 2017

Study Registration Dates

• First Submitted: June 8, 2016
• First Submitted That Met QC Criteria: June 8, 2016
• First Posted (Estimate): June 13, 2016

Study Record Updates

• Last Update Posted (Actual): May 3, 2018
• Last Update Submitted That Met QC Criteria: May 1, 2018
• Last Verified: June 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Behavioral Symptoms; Mental Disorders; Mood Disorders; Depression; Depressive Disorder
• Other Study ID Numbers: 16-5094

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO