High Dose Accelerated iTBS for Depression

NCT04255784 | Completed

• 1 other identifier: 109-2019
• Study Type: interventional
• Target: 228
• Locations: 1 country
• Sites: 2

Brief Summary

This trial will compare active intermittent theta burst stimulation (iTBS) rTMS in an accelerated treatment schedule (8 treatment sessions per day for 5 days) to a placebo control. Depression symptom severity will be measured before, during, at end of treatment, 1-week post and 4-weeks post treatment.

Conditions

Major Depressive Disorder

Keywords

depression; transcranial magnetic stimulation; treatment resistance; theta burst stimulation

Outcome Measures

Primary Outcomes (1)

• Change on the 17-item Hamilton Rating Scale for Depression (HRSD-17)

  ITT

  After 5 treatment days

Secondary Outcomes (4)

• Change on the 17-item Hamilton Rating Scale for Depression (HRSD-17)

  one week and four weeks post treatment

• Proportion of participants achieving response (50% reduction in HRSD-17) and remission (HRSD-17 <8)

  After 5 treatment days and at 1-week and 4 weeks post-treatment

• Change on the Beck Depression Inventory-II (BDI-II)

  After 5 treatment days and at 1-week and 4 weeks post-treatment

• Change on the Generalized Anxiety Disorder 7-Item (GAD-7)

  After 5 treatment days and at 1-week and 4 weeks post-treatment

Study Arms (2)

Active iTBS

EXPERIMENTAL

Administered 8 times daily at approximately 50 minutes intervals (between session end and start) for 5 days. Each session will deliver 1800 pulses of active iTBS (bursts of 3 pulses at 50 Hz, bursts repeated at 5 Hz, with a duty cycle of 2 seconds on, 8 seconds off, over 60 cycles / \~10 minutes) at a target intensity of 110% of the subject's resting motor threshold.

Device: Active iTBS

Sham iTBS

SHAM COMPARATOR

Administered 8 times daily at approximately 50 minutes intervals (between session end and start) for 5 days, using a sham coil that reproduces auditory and tactile sensations of stimulation and has an identical external appearance. Each session will deliver 1800 pulses of sham iTBS (bursts of 3 pulses at 50 Hz, bursts repeated at 5 Hz, with a duty cycle of 2 seconds on, 8 seconds off, over 60 cycles / \~10 minutes) at a target intensity of 110% of the subject's resting motor threshold.

Device: Sham iTBS

Interventions

Active iTBS DEVICE

Fluid-Cooled B70 A/P Coil with either Magventure X100 or R30

Active iTBS

Sham iTBS DEVICE

Fluid-Cooled B70 A/P Coil with either Magventure X100 or R30

Sham iTBS

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 65
• have failed to achieve a clinical response to an adequate dose of an antidepressant based on an Antidepressant Treatment History Form (ATHF) score for that antidepressant trial of \> 3 in the current episode OR have been unable to tolerate at least 2 separate trials of antidepressants of inadequate dose and duration (ATHF score of 1 or 2 on those 2 separate antidepressants)
• have a score \> 18 on the HRSD-17 item
• have had no increase or initiation of any psychotropic medication in the 4 weeks prior to screening
• able to adhere to the treatment schedule
• Pass the TMS adult safety screening (TASS) questionnaire
• have normal thyroid functioning based on pre-study blood work.

You may not qualify if:

• have a Mini-International Neuropsychiatric Interview (MINI) confirmed diagnosis 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, that is 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 subject blinding
• 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 or a febrile seizure of infancy, 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
• clinically significant laboratory abnormality, in the opinion of the one of the principal investigators or study physicians
• currently take more than lorazepam 2 mg daily (or equivalent) or any dose of an anticonvulsant due to the potential to limit rTMS efficacy
• non-correctable clinically significant sensory impairment (i.e., cannot hear well enough to cooperate with interview).

Sponsors & Collaborators

• Centre for Addiction and Mental Health: lead
• University Health Network, Toronto: collaborator
• University of British Columbia: collaborator

Study Sites (2)

University of British Columbia

Vancouver, British Columbia, V6T2A1, Canada

Location

CAMH

Toronto, Ontario, M6J1H4, Canada

Location

Related Publications (1)

• Goodman MS, Vila-Rodriguez F, Barwick M, Burke MJ, Downar J, Hunter J, Kaster TS, Knyahnytska Y, Kurdyak P, Maunder R, Thorpe K, Trevizol AP, Voineskos D, Zhang W, Blumberger DM. A randomized sham-controlled trial of high-dosage accelerated intermittent theta burst rTMS in major depression: study protocol. BMC Psychiatry. 2024 Jan 8;24(1):28. doi: 10.1186/s12888-023-05470-9.

  PMID: 38191370 DERIVED

MeSH Terms

Conditions

Depressive Disorder, Major; Depression

Condition Hierarchy (Ancestors)

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

Study Officials

• Daniel Blumberger, MD

  CAMH

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Medical Head and Co-Director, Temerty Centre for Therapeutic Brain Intervention

Study Record Dates

• First Submitted: February 3, 2020
• First Posted: February 5, 2020
• Study Start: February 6, 2020
• Primary Completion: January 24, 2025
• Study Completion: January 24, 2025
• Last Updated: January 29, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will not share

Locations

CA (2)