TBS Treatment for Treatment-Resistant Depression (TTT)

April 1, 2024 updated by: Andre R Brunoni, University of Sao Paulo

TBS Treatment for Treatment-Resistant Depression: a Randomized, Sham-Controlled Trial

Depression is a highly disabling disease that is prevalent throughout the world. The treatments proposed and studied to date have shown to be partially effective in treating this condition. Neuromodulation strategies have been used as an alternative, especially for refractory and challenging cases. In this context, studies investigating the effectiveness of transcranial magnetic stimulation, including the theta burst stimulation (TBS) modality, have been increasing in number. However, there is still a lack of information seeking to explore the maximum effectiveness in the TBS modality. Therefore, the investigators developed a new stimulation protocol consisting of 3 TBS sessions per day, with an offer of 1200 pulses per session and a 30-minute interval between sessions. The protocol will be performed for 15 days, totalizing 45 stimulation sessions. The stimulations will be directed to the left dorsolateral prefrontal cortex (F3) and will be performed in a Magventure MagPro R30 device. The investigators will select 100 patients with unipolar major depression, following previously established inclusion and exclusion criteria, and will apply the protocol randomly, dividing the patients into an active and placebo group. The research team hypothesized that the active group patients will have greater improvement in symptoms of depression assessed by the 17-item hamilton depression scale over patients of the placebo group. In addition, other scales will be used for secondary outcomes. The researchers also hypothesized that there will be no difference between patients placed in the active or placebo groups in terms of side effects.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Depression is a highly disabling disease that is prevalent throughout the world. The treatments proposed and studied to date have shown to be partially effective in treating this condition. Neuromodulation strategies have been used as an alternative, especially for refractory and challenging cases. In this context, studies investigating the effectiveness of transcranial magnetic stimulation, including the theta burst stimulation (TBS) modality, have been increasing in number. However, there is still a lack of information seeking to explore the maximum effectiveness in the TBS modality. Therefore, the investigators developed a stimulation protocol consisting of 3 TBS sessions per day, with an offer of 1200 pulses per session and a 30-minute interval between sessions. This protocol will be applied to patients for 15 days, totaling 45 stimulation sessions. The stimulations will be directed to the left dorsolateral prefrontal cortex (F3 obtained by the Beam method) and will be performed in a Magventure MagPro R30 device.

The stimulation will be delivered at 100% of the motor threshold and will last for 6 minutes. The placebo will consist of a noise generator, which makes the same noise as active stimulation, and a surface electrode placed over the patient's eyebrow, mimicking the tactile sensory effects of TBS. The researchers will select 100 patients with unipolar major depression, following previously established inclusion and exclusion criteria, and the protocol will be applied randomly, dividing the patients into an active and placebo group. Inclusion criteria are: patients with a diagnosis of unipolar major depression confirmed by the Mini International Neuropsychiatric Interview (MINI), between 18 and 59 years of age, with a Hamilton score equal to or greater than 17. In addition, patients must have undergone at least 1 first-line treatment for depression and a maximum of 3 previous unsuccessful treatments. Exclusion criteria are: other mental disorders (bipolar affective disorder, obsessive-compulsive disorder, attention deficit hyperactivity disorder, personality disorders, substance use disorder, psychotic disorders), history of suicide attempts or severe suicidal ideation in the last 6 months. In addition, patients who have a history of epilepsy, decompensated medical conditions, metallic implants in the skull or previous experience with transcranial magnetic stimulation will be excluded.

The investigators hypothesized greater improvement in the symptoms of depression in patients of the active group compared with the placebo group, assessed by the 17-item hamilton depression scale. In addition, other scales for secondary outcomes wil be used, such as the Montgomery-Asberg Depression Scale. The research team also hypothesized that there will be no difference between patients in the different groups in terms of side effects. In the patient selection process, individuals will be evaluated and submitted to questionnaires in consultations by video call with a medical doctor of the research team. During the study, patients will be evaluated weekly and in person, by professionals who are not part of the stimulation application group. The service's waiting room will be organized in a certain way, so that patients do not meet or communicate during the study. After the end of the stimulations, the patients will be followed up for another 2 weeks in order to evaluate the support of the response obtained during the investigation. All data will be stored in a secure database with an external hard drive. All ethical considerations will be discussed with patients and followed during the study. The project has already been approved by the ethics committee of the Hospital of Clinics of the University of Sao Paulo. A pilot study will be conducted to assess the feasibility of the protocol.

Study Type

Interventional

Enrollment (Actual)

100

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Brazil
      • Sao Paulo, Brazil, 05403903
        • Institute of Psychiatry - University of Sao Paulo

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 59 years (Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Inclusion criteria are: patients with a diagnosis of unipolar major depression confirmed by the MINI interview, between 18 and 59 years of age, with a Hamilton score equal to or greater than 17. In addition, patients must have undergone at least 1 first-line treatment for depression and a maximum of 3 previous unsuccessful treatments.

Exclusion Criteria:

  • Exclusion criteria are: other mental disorders (bipolar affective disorder, obsessive-compulsive disorder, attention deficit hyperactivity disorder, personality disorders, substance use disorder, psychotic disorders), history of suicide attempts or severe suicidal ideation in the last 6 months. In addition, patients who have a history of epilepsy, decompensated medical conditions, metallic implants in the skull or previous experience with transcranial magnetic stimulation will be excluded.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Active Group - protocol of Theta Burst Stimulation
3 sessions of theta burst stimulation, 1200 pulses per session of 6 minutes duration, 30-minute interval between sessions. Stimulation directed to the left dorsolateral pre-frontal cortex. The protocol will be applied for 15 days, totalizing 45 sessions of stimulation.
Procedure: Theta Burst Stimulation
3 TBS sessions per day, with an offer of 1200 pulses per session and a 30-minute interval between sessions. This protocol will be applied to patients for 15 days, totaling 45 stimulation sessions. The stimulations will be directed to the left dorsolateral prefrontal cortex (F3 obtained by the Beam method) and will be performed in a Magventure MagPro R30 device.The stimulation will be delivered at 100% of the motor threshold and will last for 6 minutes.
Other Names:
  • Transcranial Magnetic Stimulation
  • Magventure - MagPro R30
Placebo Comparator: Placebo Group - Sham Stimulation
The placebo will consist of a sham stimulation activity. A noise generator, which makes the same noise as active stimulation, and a surface electrode placed over the patient's eyebrow, mimicking the tactile sensory effects of TBS.
Procedure: Sham Stimulation
The placebo will consist of a sham stimulation activity. A noise generator, which makes the same noise as active stimulation, and a surface electrode placed over the patient's eyebrow, mimicking the tactile sensory effects of TBS. It will also occur three times a day, with a duration of 6 minutes. The interval time between procedures will be of 30 minutes. It will take place for the same 15 weekdays, totalizing 45 sham stimulations.
Other Names:
  • Placebo/Sham Stimulation

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Hamilton Depression Rating Scale (17 Items)
Time Frame: 5 weeks
Scale to assess depressive symptoms - The minimum scale score is 0 and the maximum scale score is 50 points. The standardized scores are: 7 to 17 points - mild depression; 18 to 25 points - moderate depression and 26 or more points - severe depression. Higher scores mean worse clinical condition or outcome.
5 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Montgomery-Asberg Depression Rating Scale
Time Frame: 5 weeks
Scale to assess depressive symptoms The minimum scale score is 0 and the maximum scale score is 60 points. The standardized scores are: 7 to 19 points - mild depression; 20 to 34 points - moderate depression and 35 or more points - severe depression. Higher scores mean worse clinical condition or outcome.
5 weeks
Collateral Effects Rating Scale
Time Frame: 5 weeks
Scale to assess side effects of the procedure - not a numeric scale. It consist of a scale to assess the severity of side effects between: absent, mild, moderate and severe. In addition, the investigators seek to correlate the possible side effect with the procedure in the face of the following alternatives: remotely related, possibly related, probably related, certainly related. For this, the patient's own report, will be taken into account.
5 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Sao Paulo

Investigators

  • Study Director: Andre R Brunoni, MD, PhD, University of Sao Paulo

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

June 6, 2022

Primary Completion (Actual)

January 1, 2024

Study Completion (Actual)

April 1, 2024

Study Registration Dates

First Submitted

May 13, 2022

First Submitted That Met QC Criteria

May 19, 2022

First Posted (Actual)

May 24, 2022

Study Record Updates

Last Update Posted (Actual)

April 3, 2024

Last Update Submitted That Met QC Criteria

April 1, 2024

Last Verified

April 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 52384921.6.0000.0068

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

Participant data can only be accessed by study members. Such data will be stored in a database with an external hard drive (HD). The only way to access this database is to be affiliated with the institution where the study will be conducted and to request authorization from the study director, who coordinates access for the other researchers.

During the study, each participant will be evaluated by a single professional and this professional from the research group will be the only one with conditions to add or change clinical data according to evaluation.

After data analysis and the end of the research, supplementary materials containing a database preserving the anonymity of the participants will be made available.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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