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TBS Treatment for Treatment-Resistant Depression (TTT)

Primary Purpose

Major Depressive Disorder, Unipolar Depression

Status
Recruiting
Phase
Not Applicable
Locations
Brazil
Study Type
Interventional
Intervention
Theta Burst Stimulation
Sham Stimulation
Sponsored by
University of Sao Paulo
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Major Depressive Disorder focused on measuring Unipolar Depression, Major Depressive Disorder, Transcranial Magnetic Stimulation, Neuromodulation, Theta Burst Stimulation, Accelerated Theta Burst Stimulation, Intermittent Theta Burst Stimulation

Eligibility Criteria

18 Years - 59 Years (Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Institute of Psychiatry - University of Sao PauloRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

Active Group - protocol of Theta Burst Stimulation

Placebo Group - Sham Stimulation

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

Hamilton Depression Rating Scale (17 Items)
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.

Secondary Outcome Measures

Montgomery-Asberg Depression Rating Scale
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.
Collateral Effects Rating Scale
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.

Full Information

First Posted
May 13, 2022
Last Updated
August 11, 2022
Sponsor
University of Sao Paulo
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1. Study Identification

Unique Protocol Identification Number
NCT05388539
Brief Title
TBS Treatment for Treatment-Resistant Depression
Acronym
TTT
Official Title
TBS Treatment for Treatment-Resistant Depression: a Randomized, Sham-Controlled Trial
Study Type
Interventional

2. Study Status

Record Verification Date
August 2022
Overall Recruitment Status
Recruiting
Study Start Date
June 6, 2022 (Actual)
Primary Completion Date
January 2024 (Anticipated)
Study Completion Date
June 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Sao Paulo

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Major Depressive Disorder, Unipolar Depression
Keywords
Unipolar Depression, Major Depressive Disorder, Transcranial Magnetic Stimulation, Neuromodulation, Theta Burst Stimulation, Accelerated Theta Burst Stimulation, Intermittent Theta Burst Stimulation

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
100 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Active Group - protocol of Theta Burst Stimulation
Arm Type
Active Comparator
Arm Description
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.
Arm Title
Placebo Group - Sham Stimulation
Arm Type
Placebo Comparator
Arm Description
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.
Intervention Type
Procedure
Intervention Name(s)
Theta Burst Stimulation
Other Intervention Name(s)
Transcranial Magnetic Stimulation, Magventure - MagPro R30
Intervention Description
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.
Intervention Type
Procedure
Intervention Name(s)
Sham Stimulation
Other Intervention Name(s)
Placebo/Sham Stimulation
Intervention Description
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.
Primary Outcome Measure Information:
Title
Hamilton Depression Rating Scale (17 Items)
Description
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.
Time Frame
5 weeks
Secondary Outcome Measure Information:
Title
Montgomery-Asberg Depression Rating Scale
Description
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.
Time Frame
5 weeks
Title
Collateral Effects Rating Scale
Description
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.
Time Frame
5 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
59 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Andre R Brunoni, M, PhD
Phone
+551126617585
Ext
7585
Email
brunoni@usp.br
First Name & Middle Initial & Last Name or Official Title & Degree
Matheus Rassi, MD
Email
matheusrassi10@gmail.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Andre R Brunoni, MD, PhD
Organizational Affiliation
University of Sao Paulo
Official's Role
Study Director
Facility Information:
Facility Name
Institute of Psychiatry - University of Sao Paulo
City
Sao Paulo
ZIP/Postal Code
05403903
Country
Brazil
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Andre R Brunoni, MD, PhD
Phone
551126618159
Ext
8159
Email
brunoni@usp.br

12. IPD Sharing Statement

Plan to Share IPD
No
IPD Sharing 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.
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TBS Treatment for Treatment-Resistant Depression

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