Theta-Burst Stimulation in Major Depressive Episodes With Mixed Characteristics.

October 9, 2019 updated by: Ricardo Alberto Moreno, M.D., Ph.D., University of Sao Paulo

Theta-Burst Stimulation (TBS) in Major Depressive Episodes With Mixed Characteristics in Bipolar and Major Depressive Disorder: a Randomized, Controlled, Double-blind, Parallel-group Clinical Trial of Efficacy, Safety, and Tolerability.

The investigators will perform a double-blind, randomized, sham-controlled clinical trial of theta-burst stimulation (TBS) in mixed depressive episodes of both bipolar and major depressive disorders. Will be selected 90 patients aged 18-65 years with diagnosis of TB (I or II) or MDD in moderate or severe major depressive episode with mixed features. The primary endpoint of efficacy will be a continuous outcome of change in Montgomery-Asberg Depression Rating Scale (MADRS) from baseline to week 3.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Unknown

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

INTRODUCTION: Mixed-specifier mood disorders are probably a different subgroup in terms of response to treatment, socio-demographic parameters, course and family history. The investigators will perform a clinical trial of theta-burst stimulation (TBS) in mixed depressive episodes of both bipolar (I and II) and major depressive disorders. METHODS: The study is designed as a randomized, sham-controlled, double-blinded clinical trial evaluating TBS for the treatment of moderate or severe major depressive episodes with mixed features of patients receiving at least one first or second line pharmacological treatment for depressive episodes without adequate response. Ninety adult (18 to 65 yo) patients will be enrolled and submitted to 6-week (comprising 5 consecutive days a week sessions for the first 3 weeks and then 2 days a week for a further 3 week) of inhibitory followed by excitatory TBS in dorsolateral prefrontal cortex. Participants will be assessed using clinical and neuropsychological tests before and after the intervention. The primary outcome is change in Montgomery-Asberg Depression Scale (MADRS) score over time and across groups. Cognitive parameters will also be assessed with neuropsychological tests.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Anticipated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
90

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • 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 Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

Study Locations

  • Brazil
      • Sao Paulo, Brazil, 05403-010
        • Recruiting
        • Institute of Psychiatry, University of Sao Paulo
        • Contact:
        • Contact:
        • Sub-Investigator:
          • Diego F. Tavares, MD

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

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Current mixed depression in any mood disorder (bipolar I, bipolar II or major depressive disorder) assessed with Montgomery-Asberg Depression Rating Scale (MADRS) score ≥ 20 points AND Young Mania Rating Scale (YMRS) score ≥ 1 point in 3 or more items.
  • Any appropriate first or second line pharmacological regimen in accordance with CANMAT guidelines to treat a major depressive episode in major depressive disorder (Agomelatina 25-50 mg/dia; Bupropiona 150-300 mg/dia; Citalopram 20-40 mg/dia; Desvenlafaxina 50 - 100 mg/dia; Duloxetina 60 - 120mg/dia; Escitalopram 10 - 20 mg/dia; Fluoxetina 20 - 60 mg/dia; Fluvoxamina 100 - 300 mg/dia; Mirtazapina 15 - 45 mg/dia; Paroxetina 20 - 60 mg/dia; Sertralina 50 - 200 mg/dia; Venlafaxina 75 - 225 mg/dia; Vortioxetina 10 - 20 mg/dia; Amitriptilina 150 - 300 mg/dia; Imipramina 150 - 300 mg/dia; Clomipramina 150 - 200 mg/dia; Nortriptilina 75 - 150 mg/dia; Trazodona 150 - 300 mg/dia; Quetiapina 150 - 300mg/dia), bipolar I (Quetiapina 300 - 600 mg/dia; Lítio litemia 0,6 - 1,2 mEq/L; Lamotrigina 100 - 200 mg/dia; Lurasidona 40 - 80 mg/dia; Lítio/Divalproato + Lurasidona; Lítio/Divalproato + Lamotrigina; Olanzapina 5 - 20 mg/dia + Fluoxetina 20 - 60 mg/dia; Divalproato de sódio; Lítio/Divalproato + ISRS/Bupropiona) or bipolar II disorder (Quetiapina 300 - 600 mg/dia; Lítio; Lamotrigina; Bupropiona; Sertralina; Venlafaxina).

Exclusion Criteria:

  • Concomitant diagnosis of other neuropsychiatric disorders such as: schizophrenia, dementias, mental retardation, organic mental disorder, or epilepsy;
  • Acute suicide ideation (assessed by interview and clinical evaluation);
  • Suspected or confirmed pregnancy;
  • Women in breastfeeding;
  • Severe or unstable clinical disease;
  • Specific contraindications to TBS: previous epileptic seizures; change in electroencephalogram at some point in life; previous stroke; previous severe TBI (with neurosurgery); metallic object on head (except mouth) as projectile piece, surgical clip, welding fragments; any implanted device (cardiac pacemaker, intravenous catheter).

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: Triple

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Active Comparator: Active TBS Arm
Patients randomized to this arm will receive active TBS 5 consecutive days of the week (Monday to Friday) in the first 3 weeks and then 2 alternate days of the week (with interval of at least 1 day between sessions) for another 3 weeks.
Device: Active Theta Burst Stimulation (TBS)
Each session will be comprised of ACTIVE TBS: first, continuous inhibitory stimulation (cTBS) in the right dorsolateral prefrontal cortex followed by intermittent excitatory stimulation (iTBS) in the left dorsolateral prefrontal cortex.
Sham Comparator: Sham TBS Arm
Patients randomized to this arm will receive sham TBS 5 consecutive days of the week (Monday to Friday) in the first 3 weeks and then 2 alternate days of the week (with interval of at least 1 day between sessions) for another 3 weeks.
Device: Sham Theta Burst Stimulation (TBS)
The sham-TBS sessions will be performed using an identical coil that produces SHAM Stimulation: first, sham continuous inhibitory stimulation (cTBS) in the right dorsolateral prefrontal cortex followed by sham intermittent excitatory stimulation (iTBS) in the left dorsolateral prefrontal cortex.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Change in Montgomery-Asberg Depression Rating Scale (MADRS) at week 3.
Time Frame: From baseline until week 3.
Change in Montgomery-Asberg Depression Rating Scale (MADRS) in each patient in both interventional groups. The outcome will be assessed by a continuous change using a mixed models statistic. The scale range is: 0 to 6 - normal/symptom absent; 7 to 19 - mild depression; 20 to 34 - moderate depression; 35 - 60 - severe depression. Reduction is a better and increase is a worse outcome.
From baseline until week 3.

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Change in Montgomery-Asberg Depression Rating Scale (MADRS) at week 6.
Time Frame: From baseline until week 6.
Change in Montgomery-Asberg Depression Rating Scale (MADRS) in each patient in both interventional groups. The outcome will be assessed by a continuous change using a mixed models statistic. The scale range is: 0 to 6 - normal/symptom absent; 7 to 19 - mild depression; 20 to 34 - moderate depression; 35 - 60 - severe depression. Reduction is a better and increase is a worse outcome.
From baseline until week 6.
Change in Young Mania Rating Scale (YMRS) at week 3.
Time Frame: From baseline until week 3.
Change in Young Mania Rating Scale (YMRS) in each patient in both interventional groups. The outcome will be assessed by a continuous change using a mixed models statistic. The scale range is: 13-19 - hypomania; 20-25 - mild mania; 26-37 - moderate mania ; 38-60 - severe mania. Reduction is a better and increase is a worse outcome.
From baseline until week 3.
Change in Young Mania Rating Scale (YMRS) at week 6.
Time Frame: From baseline until week 6.
Change in Young Mania Rating Scale (YMRS) in each patient in both interventional groups. The outcome will be assessed by a continuous change using a mixed models statistic. The scale range is: 13-19 - hypomania; 20-25 - mild mania; 26-37 - moderate mania ; 38-60 - severe mania. Reduction is a better and increase is a worse outcome.
From baseline until week 6.
Response rate using Montgomery-Asberg Depression Rating Scale (MADRS) at week 3
Time Frame: From baseline until week 3.
Reduction of 50% or more of the Montgomery-Asberg Depression Rating Scale (MADRS) in each patient in both interventional groups. The scale range is: 0 to 6 - normal/symptom absent; 7 to 19 - mild depression; 20 to 34 - moderate depression; 35 - 60 - severe depression. Reduction is a better and increase is a worse outcome.
From baseline until week 3.
Response rate using Montgomery-Asberg Depression Rating Scale (MADRS) at week 6.
Time Frame: From baseline until week 6.
Reduction of 50% or more of the Montgomery-Asberg Depression Rating Scale (MADRS) in each patient in both interventional groups. The scale range is: 0 to 6 - normal/symptom absent; 7 to 19 - mild depression; 20 to 34 - moderate depression; 35 - 60 - severe depression. Reduction is a better and increase is a worse outcome.
From baseline until week 6.
Remission rate using Montgomery-Asberg Depression Rating Scale (MADRS) at week 3
Time Frame: From baseline until week 3.
Montgomery-Asberg Depression Rating Scale (MADRS) < 11 points in each patient in both interventional groups. The scale range is: 0 to 6 - normal/symptom absent; 7 to 19 - mild depression; 20 to 34 - moderate depression; 35 - 60 - severe depression. Reduction is a better and increase is a worse outcome.
From baseline until week 3.
Remission rate using Montgomery-Asberg Depression Rating Scale (MADRS) at week 6.
Time Frame: From baseline until week 6.
Montgomery-Asberg Depression Rating Scale (MADRS) < 11 points in each patient in both interventional groups. The scale range is: 0 to 6 - normal/symptom absent; 7 to 19 - mild depression; 20 to 34 - moderate depression; 35 - 60 - severe depression. Reduction is a better and increase is a worse outcome.
From baseline until week 6.
Change in Hamilton Anxiety Scale (HAM-A scale) at week 3.
Time Frame: From baseline until week 3.
Change in Hamilton Anxiety Scale (HAM-A scale) in each patient in both interventional groups. The outcome will be assessed by a continuous change using a mixed models statistic. The scale range is: 0-17 - mild anxiety; 18-24 moderate anxiety; 25-30 - severe anxiety. Reduction is a better and increase is a worse outcome.
From baseline until week 3.
Change in Hamilton Anxiety Scale (HAM-A scale) at week 6.
Time Frame: From baseline until week 6.
Change in Hamilton Anxiety Scale (HAM-A scale) in each patient in both interventional groups. The outcome will be assessed by a continuous change using a mixed models statistic. The scale range is: 0-17 - mild anxiety; 18-24 moderate anxiety; 25-30 - severe anxiety. Reduction is a better and increase is a worse outcome.
From baseline until week 6.
Change in Global Clinical Impression Scale of Severity (GCI-S) at week 3.
Time Frame: From baseline until week 3.
Change in Global Clinical Impression Scale of Severity (GCI-S) in each patient in both interventional groups. The outcome will be assessed by a continuous change using a mixed models statistic. The scale range is: 1- not sick; 2- very mild disease; 3- mild disease; 4- moderate disease; 5- intense disease; 6- severe disease; 7- extremely severe disease. Reduction is a better and increase is a worse outcome.
From baseline until week 3.
Change in Global Clinical Impression Scale of Severity (GCI-S) at week 6.
Time Frame: From baseline until week 6.
Change in Global Clinical Impression Scale of Severity (GCI-S) in each patient in both interventional groups. The outcome will be assessed by a continuous change using a mixed models statistic. The scale range is: 1- not sick; 2- very mild disease; 3- mild disease; 4- moderate disease; 5- intense disease; 6- severe disease; 7- extremely severe disease. Reduction is a better and increase is a worse outcome.
From baseline until week 6.
Change in the brief version of the World Health Organization Quality of Life Questionnaire (WHOQOL-brief scale) at week 3.
Time Frame: From baseline until week 3.
Change in the brief version of the World Health Organization Quality of Life Questionnaire (WHOQOL-brief scale) in both interventional groups.The scale range is: 26 to 130 points. Increase is a better and reduction is a worse outcome.
From baseline until week 3.
Change in the brief version of the World Health Organization Quality of Life Questionnaire (WHOQOL-brief scale) at week 6.
Time Frame: From baseline until week 6.
Change in the brief version of the World Health Organization Quality of Life Questionnaire (WHOQOL-brief scale) in both interventional groups.The scale range is: 26 to 130 points. Increase is a better and reduction is a worse outcome.
From baseline until week 6.
Change in Global Assessment of Functioning (GAF) Scale at week 3.
Time Frame: From baseline until week 3.
Change in Global Assessment of Functioning (GAF) Scale in both interventional groups. The scale range is: 1 to 100 points. Increase is a better and reduction is a worse outcome.
From baseline until week 3.
Change in Global Assessment of Functioning (GAF) Scale at week 6.
Time Frame: From baseline until week 6.
Change in Global Assessment of Functioning (GAF) Scale in both interventional groups. The scale range is: 1 to 100 points. Increase is a better and reduction is a worse outcome.
From baseline until week 6.
Change in Biological Rhythm Interview of Assessment in Neuropsychiatry (BRIAN) at week 3.
Time Frame: From baseline until week 3.
Change in Biological Rhythm Interview of Assessment in Neuropsychiatry (BRIAN) in both interventional groups. The scale range is: 18 to 72 points. Reduction is a better and increase is a worse outcome.
From baseline until week 3.
Change in Biological Rhythm Interview of Assessment in Neuropsychiatry (BRIAN) at week 6.
Time Frame: From baseline until week 6.
Change in Biological Rhythm Interview of Assessment in Neuropsychiatry (BRIAN) in both interventional groups. The scale range is: 18 to 72 points. Reduction is a better and increase is a worse outcome.
From baseline until week 6.
Change in Barratt Impulsivity Scale of 11 items (BIS-11) at week 3.
Time Frame: From baseline until week 3.
Change in Barratt Impulsivity Scale of 11 items (BIS-11) in both interventional groups. The scale range is: 30 to 120 points. Reduction is a better and increase is a worse outcome.
From baseline until week 3.
Change in Barratt Impulsivity Scale of 11 items (BIS-11) at week 6.
Time Frame: From baseline until week 6.
Change in Barratt Impulsivity Scale of 11 items (BIS-11) in both interventional groups. The scale range is: 30 to 120 points. Reduction is a better and increase is a worse outcome.
From baseline until week 6.
Frequency of adverse events in UKU-SERS Scale at week 6.
Time Frame: From baseline until week 6.
Frequency of adverse events in UKU-SERS Scale in both interventional groups.The scale range is: 0 to 57 points. Reduction is a better and increase is a worse outcome.
From baseline until week 6.

Collaborators and Investigators

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

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
University of Sao Paulo

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Ricardo Moreno, 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

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)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
March 8, 2019

Primary Completion (Anticipated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
March 1, 2021

Study Completion (Anticipated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
May 1, 2021

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
October 2, 2019

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 9, 2019

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
October 10, 2019

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
October 10, 2019

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 9, 2019

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
October 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • MORENO-2019

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

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.

Cookie Settings

We use cookies to ensure that we give you the best experience on our website. For more details carefully read our Privacy and Cookies Policy. ...>>>You can change your preferences or withdraw your consent at any time by deleting the cookies from your website or computer as described in the policy. Please accept it and choose your preferences by ticking the corresponding boxes in the "Manage Settings" section below. Please carefully read our Terms of Service before you proceed with using any part of this website.
«Manage Settings