Biomarkers of Theta Burst Stimulation in Major Depressive Disorder

NCT ID: NCT03626181

Last Updated: 2018-08-10

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: NA
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-07-06
• Study Completion Date: 2019-07-01

Brief Summary

This study investigates the brain-based biomarkers of treatment response to accelerated theta burst stimulation (aTBS) in patients with Major Depressive Disorder resistant to pharmacological treatment(MDD) in an open label design.

Detailed Description

Theta burst stimulation (TBS) is a newer form of rTMS which requires less stimulation time and produces longer lasting post-stimulation effects in the cerebral cortex (4). It has been shown to be effective in inducing synaptic plasticity and has similar or better efficacy in treating depression compared to rTMS (4).Newer accelerated TBS (aTBS) protocols that condense stimulation sessions down to several days rather than weeks have shown similar response rates when compared to prolonged TBS protocols, also with similar tolerability and safety. In order to develop aTBS as an effective treatment for MDD, future research should focus on identification of reliable predictors for better outcome to TBS. The main objectives were: 1) To directly compare multiple different brain-based measures (neuroimaging and electrophysiology) to identify which has the most power in accurately predicting response to TBS compared to sham. 2) To track both short and long-term longitudinal electrophysiological (EEG) changes related to the therapeutic effects of TBS.

Conditions

Depressive Disorder, Treatment-Resistant

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Active TBS-DLPFC

There is only one arm. All participants will receive Theta Burst Stimulation (transcranial magnetic stimulation) of the dorsolateral prefrontal cortex.

Group Type: EXPERIMENTAL

Theta Burst Stimulation ( Transcranial Magnetic Stimulation)

Intervention Type: DEVICE

Participants will receive bilateral TBS, 5 times daily (15 minutes between), over 5 consecutive days (25 sessions total). In each session they will receive intermittent TBS (iTBS) over left dorsolateral prefrontal cortex (DLPFC), followed by continuous TBS (cTBS) over right DLPFC. Stimulation sites will be targeted with the Localite neuronavigation system and Visor2 software, and according to Talairach coordinates in relation to individual MRIs. Intensity will be standardized at 120% of RMT.

The MagPro stimulator will deliver iTBS over left DLPFC with 1620 pulses in 54 triplet bursts (5Hz) with train duration of 2 seconds, and intertrain interval of 8 seconds. cTBS over right DLPFC will consist of 1620 pulses in 54 triplet bursts, train duration of 2 seconds, with no intertrain interval.

Interventions

Theta Burst Stimulation ( Transcranial Magnetic Stimulation)

Participants will receive bilateral TBS, 5 times daily (15 minutes between), over 5 consecutive days (25 sessions total). In each session they will receive intermittent TBS (iTBS) over left dorsolateral prefrontal cortex (DLPFC), followed by continuous TBS (cTBS) over right DLPFC. Stimulation sites will be targeted with the Localite neuronavigation system and Visor2 software, and according to Talairach coordinates in relation to individual MRIs. Intensity will be standardized at 120% of RMT.

The MagPro stimulator will deliver iTBS over left DLPFC with 1620 pulses in 54 triplet bursts (5Hz) with train duration of 2 seconds, and intertrain interval of 8 seconds. cTBS over right DLPFC will consist of 1620 pulses in 54 triplet bursts, train duration of 2 seconds, with no intertrain interval.

Intervention Type: DEVICE

Eligibility Criteria

Inclusion Criteria

1. Participant must meet the DSM-5 diagnostic criteria for single-episode Major Depressive Disorder (MDD).

2. Participant must have failed to respond to >1 but <4 classes of oral antidepressant treatments in the current episode of depression.

3. Participant must have a HAMD total score of at least 18

Exclusion Criteria

1. The participant's depressive symptoms have previously demonstrated nonresponse to:

• An adequate course of rTMS/TBS over DLPFC in the current major depressive episode, defined as at least 3 weeks of treatment, 5 times weekly
• An adequate course of treatment with electroconvulsive therapy (ECT) in the current major depressive episode, defined as at least 7 treatments with unilateral/bilateral ECT.

2. Participant has received vagal nerve stimulation (VNS) or has received deep brain stimulation (DBS) in the current episode of depression.

3. Participant has a current or prior DSM-5 diagnosis of Axis I comorbidities, including psychosis, bipolar disorder, obsessive compulsive disorder, based upon clinical assessment and confirmed by the MINI.

4. Participant has a current or prior DSM-5 diagnosis of Axis II comorbidities, including severe borderline personality disorders, antisocial, schizotypal, schizoid personality disorders based upon clinical assessment and confirmed by the MINI.

5. Participant has severe suicidal ideation/plan/ intent.

6. Participant has a history of moderate or severe substance or alcohol use disorder according to DSM-5 criteria.

7. Participant has a current or past history of seizures and neurological problems, e.g. head injury, stroke, progressive neurological disorder and complicated and unstable medical disorders, e.g. cardiovascular-related conditions, diabetes.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Calgary

OTHER

Sponsor Role: lead

Responsible Party

Rajamannar Ramasubbu

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Rajamannar Ramasubbu, MD,FRCPC,MSc

Role: PRINCIPAL_INVESTIGATOR

University of Calgary, Department of Psychiatry

Locations

University of Calgary

Calgary, Alberta, Canada

Site Status: RECRUITING

Countries

Canada

Central Contacts

Rajamannar Ramasubbu, MD,FRCPC,MSc

Role: CONTACT

rramasub@ucalgary.ca

403-210-6890

Laina B McAusland, RN,MSc

Role: CONTACT

lbsorens@ucalgary.ca

403-210-6905

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Other Identifiers

RT # 10016954

Identifier Type: OTHER

Identifier Source: secondary_id

10001858

Identifier Type: -

Identifier Source: org_study_id