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

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ClinicalTrials.gov Identifier: NCT04123301
Recruitment Status : Recruiting
First Posted : October 10, 2019
Last Update Posted : October 10, 2019
Sponsor:
Information provided by (Responsible Party):
Ricardo Alberto Moreno, M.D., Ph.D., University of Sao Paulo

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Depressive Episode Depressive Disorder Bipolar Disorder Device: Active Theta Burst Stimulation (TBS) Device: Sham Theta Burst Stimulation (TBS) Not Applicable

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 90 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Double-blind, randomized, parallel-group, 6-week, sham-controlled clinical trial.
Masking: Triple (Participant, Care Provider, Investigator)
Masking Description: Allocation masking will be done through sequentially numbered cards that will determine which group each patient will belong to. The card determines whether the coil to be used will produce actual or simulated stimulation. A secretary who does not participate directly in the research will be responsible for handling the numbered cards to the patient prior to each session. Participants and staff will not fully know the status of allocation groups.
Primary Purpose: Treatment
Official Title: 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.
Actual Study Start Date : March 8, 2019
Estimated Primary Completion Date : March 1, 2021
Estimated Study Completion Date : May 1, 2021

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
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.




Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. 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.

  2. 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.

  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.

  4. 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.

  5. 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.

  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.

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. 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.

  16. 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.

  17. 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.

  18. 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.

  19. 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.

  20. 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.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04123301


Contacts
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Contact: Diego Tavares, MD +5511941854053 diego.tavares@hc.fm.usp.br
Contact: Carla Garcia, MD +5511982732856 dracarlagarcia@gmail.com

Locations
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Brazil
Institute of Psychiatry, University of Sao Paulo Recruiting
Sao Paulo, Brazil, 05403-010
Contact: Ricardo A. Moreno, MD, PhD    +55 (11) 2661-6648    ricardoalbertomoreno@gmail.com   
Contact: Frederico N. Demetrio, MD, PhD    +55 (11) 2661-6648    frdemetr@uol.com.br   
Sub-Investigator: Diego F. Tavares, MD         
Sponsors and Collaborators
University of Sao Paulo
Investigators
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Principal Investigator: Ricardo Moreno, PHD University of Sao Paulo

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Responsible Party: Ricardo Alberto Moreno, M.D., Ph.D., Principal investigator, University of Sao Paulo
ClinicalTrials.gov Identifier: NCT04123301     History of Changes
Other Study ID Numbers: MORENO-2019
First Posted: October 10, 2019    Key Record Dates
Last Update Posted: October 10, 2019
Last Verified: October 2019

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Ricardo Alberto Moreno, M.D., Ph.D., University of Sao Paulo:
mixed depression
depressive disorder
bipolar disorder
transcranial magnetic stimulation
Additional relevant MeSH terms:
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Disease
Depressive Disorder
Depression
Bipolar Disorder
Pathologic Processes
Mood Disorders
Mental Disorders
Behavioral Symptoms
Bipolar and Related Disorders