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Accelerated High-dose Sequential Bilateral Theta Burst Stimulation for Treatment Resistant Depression

U

University of Calgary

Status

Not yet enrolling

Conditions

Treatment Resistant Depression

Treatments

Device: Sequential bilateral theta burst stimulation

Study type

Interventional

Funder types

Other

Identifiers

NCT05811104
10021798

Details and patient eligibility

About

Repetitive transcranial magnetic stimulation (rTMS) and Theta burst stimulation (TBS) are approved by the US. Food and Drug administration (FDA) for the treatment of refractory major depression. TBS is more efficient than rTMS as it requires shorter stimulation time.Studies suggest that the efficacy of TBS could be enhanced and expedited by accelerated protocols (more than once daily sessions) with higher doses of stimulation (>600 TBS pulses up to 3600 pulses per session) and shorter duration of treatment (4-10days). The main objective of this study is to determine the clinical efficacy and safety of accelerated high dose bilateral TBS treatment for patients with treatment resistant depression in comparison to sham stimulation using a randomized double blind clinical trial design.

Full description

Major depressive disorder (MDD) accounts for the highest global burden of all mental health disorders, and approximately 50% of depressed patients meet criteria for treatment resistant of depression. Stimulation based therapies have recently become a promising alternative for patients with treatment resistant depression. Repetitive transcranial magnetic stimulation (rTMS) of the dorsolateral prefrontal cortex (DLPFC) is approved by the US. Food and Drug administration (FDA) and has been recommended as a viable treatment option for major depression. Recently, a newer form of rTMS called Theta burst stimulation (TBS) is approved by FDA as it has shown comparable clinical efficacy and safety to rTMS in the treatment of depression. TBS is more efficient than rTMS as it requires shorter stimulation time of ≤ 6min compared to 20-40 min required in conventional rTMS protocol and produces equivalent antidepressant responses.

Studies suggest that the efficacy of TBS could be enhanced and expedited by accelerated protocols (more than once daily sessions ranging from 2-10 sessions/day) higher doses of stimulation (>600 TBS pulses up to 3600 pulses per session) with shorter duration of treatment (4-10days). Recently, an accelerated Stanford Neuromodulation Therapy protocol (10 sessions of iTBS a day for 5 days) with high dose stimulation (90,000 pulses in total) was found to be more effective than sham for severe TRD. This protocol yielded robust results with 69.2% response rates compared to 13% in sham during the 4-week outcome period .

The main goal of this project is to determine the clinical efficacy and safety of accelerated high dose bilateral TBS treatment for TRD in comparison to sham stimulation using a randomized double blind clinical trial design. The second objective is to examine the durability of antidepressant effect of this treatment protocol. Our initial open label study of accelerated high dose bilateral TBS demonstrated efficacy in a small cohort of participants with TRD. This proposed study builds on our initial findings whether the antidepressant efficacy of accelerated high dose bilateral TBS would be significantly greater than an identical schedule of sham stimulation. This pilot study will help to examine the feasibility, acceptability, and tolerability of treatment protocol, and estimate the sample size for the next pivotal trial. Hypotheses: Accounting this is a pilot study using small sample size without power size calculations, it is not designed for hypothesis testing. However, it is predicted that the accelerated bilateral TBS would be clinically effective and safe in the treatment of patients with TRD compared to sham stimulation. Additionally, it is anticipated that the antidepressant effects of this treatment may be durable.

Enrollment

40 estimated patients

Sex

All

Ages

18 to 65 years old

Volunteers

No Healthy Volunteers

Inclusion criteria

  • Diagnosis of MDD (DSM-V)
  • Adults in the age range of 18 - 65
  • Both sex
  • HAMD-17 score of ≥20
  • TRD - failure to two antidepressant trial Stage II (Thase and Rush classification)

Exclusion criteria

  • Post traumatic stress disorder,
  • Obsessive compulsive disorder,
  • Psychosis
  • Bipolar disorder,
  • substance abuse disorder,
  • autistic spectrum disorder,
  • active suicidal behavior
  • Epilepsy
  • Dementia,
  • Movement disorders
  • severe head injury
  • Brain metallic implants, cardiac pacemakers
  • Pregnancy .
  • Non-response to prior rTMS, Electroconvulsive treatment, Vagal nerve or Deep brain stimulation or a history of psychosurgery.
  • Borderline personality disorder,
  • Schizotypal, schizoid & paranoid personality disorder
  • Current treatment with anticonvulsants or benzodiazepines

Trial design

Primary purpose

Treatment

Allocation

Randomized

Interventional model

Parallel Assignment

Masking

Triple Blind

40 participants in 2 patient groups

Active stimulation
Experimental group
Description:
Bilateral real TBS
Treatment:
Device: Sequential bilateral theta burst stimulation
Sham stimulation
Sham Comparator group
Description:
Bilateral Sham stimulation
Treatment:
Device: Sequential bilateral theta burst stimulation

Trial contacts and locations

0

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Central trial contact

Rajamannar Ramasubbu, MD

Data sourced from clinicaltrials.gov

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