Treatment of Bipolar Depression With H1-Coil Deep Brain rTMS: Clinical-Cognitive and Safety Evaluation (rTMSH1Coil)

November 20, 2016 updated by: Andre Brunoni, University of Sao Paulo

Evaluation Clinical, Cognitive and Safety in the Treatment of Bipolar Depression With H1-Coil Deep Transcranial Magnetic Stimulation

The treatment of bipolar disorders is always a challenge in daily practice. Mood stabilizers are partially effective in the treatment of depressive phase of the illness, although there are some reports relating to the antidepressant properties of these drugs. Other conventional methods (pharmacological) and non- conventional treatment are not effective or involve risks and side effects. Several studies with Transcranial Magnetic Stimulation (TMS) showed that magnetic stimulation daily over the left prefrontal cortex may improve the mood of patients. TMS is a noninvasive method of stimulating the brain. The instrument used nowadays in local research and application Clinical is a metallic coil formed in figure 8 (coil format 8). This instrument was capable of stimulating only surface areas of the brain, primarily the cerebral cortex, at depths of up to 3 inches below the scalp. From this angle, there is clearly a need for a means of producing magnetic fields which can reach deeper brain areas, such as those involved in mood disorders. TMS has little, if any effect in these brain areas. To this end, new coils, calls "H", that promote the stimulation of deep brain areas were developed in collaboration with the National Institute of Health (NIH) in the USA. This new coil - H1 that will be evaluated in this study has been tested for safety in NIH in 2003 by Dr. Abraham Zangen. Yet there are very few prospective clinical, randomized and controlled trials, on the effects of early and late in clinical-cognitive condition and safety of TMS with H1 coils in treating episodes of bipolar depression. The application of EMT with H1 coils can reach deepest regions of the brain and improve the clinical and cognitive condition of subjects with episodes of bipolar depression, and may be confirmed as a safe and virtually free of side effects. By an absence of treatment actually effective for bipolar depression, this study will show whether there are clinical and cognitive benefits of deep TMS with H1 coil in patients with bipolar depression.

Study Overview

Status

Status

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

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

The present research protocol will evaluate clinical-cognitive and safety effects of H1-Coil Deep Brain Transcranial Magnetic Stimulation over prefrontal cortex in subjects with bipolar depression, currently treated with mood stabilizer and/or antipsychotics for stabilization and sleep regulation. Patients will be clinically evaluated with the Diagnostic and Statistical Manual of Mental Disorders 5th Edition (DSM-5) criteria for Bipolar Depressive Episode. Symptoms intensity will be rated according to The Hamilton Depression Scale (HAMD -17 items) - main outcome. Patients with scores higher than 18 will be included and the cognitives functions will be evaluated according with tasks of neuropsychologic battery chosen. Patients with active neurological or severe disorders (such as cancer, auto-imune and cardiologic disorders) will be excluded. The present study is a double-blinded, controlled, randomized trial with 50 patients in bipolar depression episode. The intervention protocol consist in 20 consecutive daily deep TMS sessions (skipping the weekend). After meeting eligibility criteria, patients will be randomized (computer generated list) to one of the two intervention groups: 25 patients in Active H1-Coil deep brain rTMS group and Sham H1-Coil deep brain rTMS group. H1-Coil deep brain rTMS sessions will follow the following steps: the first day of treatment, patients will be instructed to wear earplugs to minimize the risk of impaired hearing. Then, the threshold intensity of stimulation motor is determined by applying pulses only to the motor cortex. The stimulation threshold is determined pro gradually increase the stimulation intensity every 5 seconds. The stimulation threshold is defined as stimulation of lesser intensity that can evoked motor potential with at least 50μV amplitude of at least 5 tentativas.A coil is positioned to 5 centimeters below the hot spot (in the prefrontal area) intensity - 120% of the threshold engine. Each session will receive 55 groups of stimuli, duration - 2/2 , frequency - 18 Hz , area - left prefrontal , intervals - 20 seconds . Soon, 1,980 pulses of magnetic stimulation will be administered every day (per session), totaling 39,600 pulses throughout treatment. Patients will be clinically assessed at baseline, weekly during the four weeks of treatment and for four weeks after completion of treatment ending in 8 weeks. Main outcome will be based on HAMD-17 items at a endpoint of 4-weeks and follow up 4-weeks, with secondary outcomes assessing Young Mania Rating Scale (11 items) at 8 weeks. Other evaluation scales include, Hamilton Anxiety Scale, Global Assessment Scale and Clinical Global Impression at 8 weeks. The cognitive assessment will be performed with a neuropsychologic battery tests at baseline, endpoint of 4-weeks and endpoint of 8-weeks with a trained neuropsychologist. Also a Safety Deep rTMS Scale, adverse effects scales and clinical evaluation with a trained physician.

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 (Actual)

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.
50

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 Locations

  • Brazil
      • São Paulo, Brazil, 05403-010
        • Department of Psychiatry - University of Sao Paulo Medical School

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

14 years to 61 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria: Outpatients

  • Diagnosed by two senior psychiatrists as suffering from bipolar depression (BP1, BP2) episode according to DSM IV using the Structured Clinical Interview for DSM-4 (SCID), with additional requirement of duration for the current episode ≥ 4 weeks and CGI ≥ 4.
  • First Stimulation threshold: intensity ≤ 70% of the threshold engine.
  • Rating on HAM-D (17 items) >18 at the screening visit.
  • Age: 18-65 years.
  • Gave informed consent for participation in the study.
  • Negative answers on safety screening questionnaire for transcranial magnetic stimulation
  • Taking mood stabilizing medication (e.g., lithium) on an acceptable range of dosage according to recent blood examination or antipsychotic medication as mood stabilizers prescribed by their treating physician
  • According to the treating physician the patient is compliant in taking the mood-stabilizing medication.
  • Medication resistance to at least two different antidepressant treatments, defined as resistance to a minimum of 2 antidepressant drug trials of adequate dose and duration in the current episode or previous episodes defined as a minimum level of 3 on the ATHF per antidepressant drug-trial.
  • Patients who have not completed antidepressant trials of adequate dose and duration due to intolerance to therapy may be included if they have demonstrated intolerance to 3 or more anti-depressant medications in the current or a previous episodes.
  • If currently taking antidepressant pharmacotherapy, must be clinically appropriate to discontinue treatment with those agents.
  • Able to tolerate psychotropic medication washout and no psychotropics during the H-coil deep brain rTMS other than benzodiazepine at equivalent dose of up to 3 mg lorazepam every day.
  • Right hand dominance.

Exclusion Criteria: Diagnosis as suffering from other diagnosis on axis 1 (like: schizophrenia, geriatric depression).

  • Diagnosis as suffering from Severe Borderline Personality Disorder or hospitalized due to exacerbation related to of borderline personality disorder.
  • Substantial suicidal risk as judged by the treating psychiatrist.
  • Attempted suicide in the past year.
  • Patients with a bipolar cycle of less than 30 days.
  • History of epilepsy or seizure in first degree relatives.
  • History of head injury.
  • History of any metal in the head (outside the mouth).
  • Known history of any metallic particles in the eye, implanted cardiac pacemaker or any intracardiac lines, implanted neurostimulators, surgical clips or any medical pumps.
  • History of frequent or severe headaches.
  • History of migraine.
  • History of hearing loss.
  • Known history of cochlear implants.
  • History of substance abuse within the past 6 months (except nicotine and caffeine) or alcoholism.
  • Pregnancy or not using a reliable method of birth control.
  • Unstable Systemic and metabolic disorders.
  • Unstable neurological or medical disease.
  • Inadequate communication with the patient.
  • Under custodial care.
  • Participation in current clinical study or clinical study within 30 days prior to this study.
  • Participants who suffer from an unstable physical disease such as high blood pressure or acute, unstable cardiac disease
  • Use of fluoxetine within 6 weeks of the baseline visit
  • Use of a Monoamine Oxidase Inhibitor (MAOI) within 2 weeks of the baseline visit
  • Current use of antidepressant medications during the course of the trial.
  • Current use of Leponex (Clozapine).
  • Previous treatment with TMS
  • Women who are breast-feeding
  • Known or suspected pregnancy
  • Women of childbearing potential and not using a medically accepted form of contraception when engaging in sexual intercourse.

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: Double

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.
Experimental: Active H1-Coil deep brain rTMS

Deep Brain Transcranial Magnetic Stimulation

18Hz Active H1-Coil deep brain rTMS for 4-weeks over the cortex prefrontal. n=25
Device: Deep Brain Transcranial Magnetic Stimulation
H1-Coil deep brain rTMS at cortex prefrontal.
Other Names:
  • H1-Coil deep brain rTMS;
  • H1-Coil.
Experimental: Sham H1-Coil deep brain rTMS

Deep Brain Transcranial Magnetic Stimulation

Sham H1-Coil deep brain rTMS for 4-weeks over the cortex prefrontal. n=25
Device: Deep Brain Transcranial Magnetic Stimulation
H1-Coil deep brain rTMS at cortex prefrontal.
Other Names:
  • H1-Coil deep brain rTMS;
  • H1-Coil.

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
Hamilton Rating Scale for Depression, 17 items (HAMD17)
Time Frame: Weeks 0, 4 and 8
Reduction of depressive symptoms as assessed by HAMD17
Weeks 0, 4 and 8

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
Young Mania Rating Scale (11 items)
Time Frame: During the eight weeks
safety: to control manic symptoms.
During the eight weeks

Other Outcome Measures

Other Outcome Measures

For clinical trials, a planned measurement described in the protocol that is used to determine the effect of an intervention/treatment on participants. For observational studies, a measurement or observation that is used to describe patterns of diseases or traits, or associations with exposures, risk factors, or treatment. Types of outcome measures include primary outcome measure and secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Neuropsychologic Battery Tasks
Time Frame: week 0, 4 and 8
A set of tests for cognitive functions such as attention, memory, mental flexibility, processing speed, reaction time, visuo-spacial perception, executive functions and language that, often show deficits in patients with bipolar depression.
week 0, 4 and 8

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

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Brainsway

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.
  • Study Director: Andre B Brunoni, Phd, Department and Institute of Psychiatry, General Hospital, University of Sao Paulo medical school

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

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.
February 1, 2014

Primary Completion (Actual)

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.
July 1, 2016

Study Completion (Actual)

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.
November 1, 2016

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 10, 2013

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 11, 2013

First Posted (Estimate)

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 14, 2013

Study Record Updates

Last Update Posted (Estimate)

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.
November 22, 2016

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.
November 20, 2016

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.
November 1, 2016

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.
  • 150.067/12

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