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

NCT01962350 | Completed DMC

• 1 other identifier: 150.067/12
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Bipolar Depression

Keywords

Deep Brain Transcranial Magnetic Stimulation;; H1-Coil deep brain rTMS;; H1-Coil;; Bipolar Depression;; Cognition.

Outcome Measures

Primary Outcomes (1)

• Hamilton Rating Scale for Depression, 17 items (HAMD17)

  Reduction of depressive symptoms as assessed by HAMD17

  Weeks 0, 4 and 8

Secondary Outcomes (1)

• Young Mania Rating Scale (11 items)

  During the eight weeks

Other Outcomes (1)

• Neuropsychologic Battery Tasks

  week 0, 4 and 8

Study Arms (2)

Active H1-Coil deep brain rTMS

EXPERIMENTAL

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

Sham H1-Coil deep brain rTMS

EXPERIMENTAL

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

Interventions

Deep Brain Transcranial Magnetic Stimulation DEVICE

H1-Coil deep brain rTMS at cortex prefrontal.

Also known as: H1-Coil deep brain rTMS;, H1-Coil.

Active H1-Coil deep brain rTMS; Sham H1-Coil deep brain rTMS

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Sao Paulo: lead
• Brainsway: collaborator

Study Sites (1)

Department of Psychiatry - University of Sao Paulo Medical School

São Paulo, São Paulo, 05403-010, Brazil

Location

Related Publications (12)

• Rosenberg O, Isserles M, Levkovitz Y, Kotler M, Zangen A, Dannon PN. Effectiveness of a second deep TMS in depression: a brief report. Prog Neuropsychopharmacol Biol Psychiatry. 2011 Jun 1;35(4):1041-4. doi: 10.1016/j.pnpbp.2011.02.015. Epub 2011 Feb 24.

  PMID: 21354242 BACKGROUND

• Rosenberg O, Roth Y, Kotler M, Zangen A, Dannon P. Deep transcranial magnetic stimulation for the treatment of auditory hallucinations: a preliminary open-label study. Ann Gen Psychiatry. 2011 Feb 9;10(1):3. doi: 10.1186/1744-859X-10-3.

  PMID: 21303566 BACKGROUND

• Rosenberg O, Zangen A, Stryjer R, Kotler M, Dannon PN. Response to deep TMS in depressive patients with previous electroconvulsive treatment. Brain Stimul. 2010 Oct;3(4):211-7. doi: 10.1016/j.brs.2009.12.001. Epub 2009 Dec 30.

  PMID: 20965450 BACKGROUND

• Rosenberg O, Shoenfeld N, Zangen A, Kotler M, Dannon PN. Deep TMS in a resistant major depressive disorder: a brief report. Depress Anxiety. 2010 May;27(5):465-9. doi: 10.1002/da.20689.

  PMID: 20455247 BACKGROUND

• Levkovitz Y, Roth Y, Harel EV, Braw Y, Sheer A, Zangen A. A randomized controlled feasibility and safety study of deep transcranial magnetic stimulation. Clin Neurophysiol. 2007 Dec;118(12):2730-44. doi: 10.1016/j.clinph.2007.09.061. Epub 2007 Oct 30.

  PMID: 17977787 BACKGROUND

• Roth Y, Amir A, Levkovitz Y, Zangen A. Three-dimensional distribution of the electric field induced in the brain by transcranial magnetic stimulation using figure-8 and deep H-coils. J Clin Neurophysiol. 2007 Feb;24(1):31-8. doi: 10.1097/WNP.0b013e31802fa393.

  PMID: 17277575 BACKGROUND

• Poon SH, Sim K, Sum MY, Kuswanto CN, Baldessarini RJ. Evidence-based options for treatment-resistant adult bipolar disorder patients. Bipolar Disord. 2012 Sep;14(6):573-84. doi: 10.1111/j.1399-5618.2012.01042.x.

  PMID: 22938165 BACKGROUND

• Bersani FS, Minichino A, Enticott PG, Mazzarini L, Khan N, Antonacci G, Raccah RN, Salviati M, Delle Chiaie R, Bersani G, Fitzgerald PB, Biondi M. Deep transcranial magnetic stimulation as a treatment for psychiatric disorders: a comprehensive review. Eur Psychiatry. 2013 Jan;28(1):30-9. doi: 10.1016/j.eurpsy.2012.02.006. Epub 2012 May 3.

  PMID: 22559998 BACKGROUND

• Loo C, Katalinic N, Mitchell PB, Greenberg B. Physical treatments for bipolar disorder: a review of electroconvulsive therapy, stereotactic surgery and other brain stimulation techniques. J Affect Disord. 2011 Jul;132(1-2):1-13. doi: 10.1016/j.jad.2010.08.017. Epub 2010 Sep 21.

  PMID: 20858566 BACKGROUND

• Richieri R, Adida M, Dumas R, Fakra E, Azorin JM, Pringuey D, Lancon C. [Affective disorders and repetitive transcranial magnetic stimulation: Therapeutic innovations]. Encephale. 2010 Dec;36 Suppl 6:S197-201. doi: 10.1016/S0013-7006(10)70057-9. French.

  PMID: 21237356 BACKGROUND

• Bersani FS, Girardi N, Sanna L, Mazzarini L, Santucci C, Kotzalidis GD, Sani G, De Rossi P, Raccah RN, Caltagirone SS, Battipaglia M, Capezzuto S, Bersani G, Girardi P. Deep transcranial magnetic stimulation for treatment-resistant bipolar depression: a case report of acute and maintenance efficacy. Neurocase. 2013;19(5):451-7. doi: 10.1080/13554794.2012.690429. Epub 2012 Jul 24.

  PMID: 22827578 RESULT

• Harel EV, Zangen A, Roth Y, Reti I, Braw Y, Levkovitz Y. H-coil repetitive transcranial magnetic stimulation for the treatment of bipolar depression: an add-on, safety and feasibility study. World J Biol Psychiatry. 2011 Mar;12(2):119-26. doi: 10.3109/15622975.2010.510893. Epub 2010 Sep 21.

  PMID: 20854181 RESULT

MeSH Terms

Conditions

Bipolar Disorder

Condition Hierarchy (Ancestors)

Bipolar and Related Disorders; Mood Disorders; Mental Disorders

Study Officials

• Andre B Brunoni, Phd

  Department and Institute of Psychiatry, General Hospital, University of Sao Paulo Medical School

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD, PhD

Study Record Dates

• First Submitted: October 10, 2013
• First Posted: October 14, 2013
• Study Start: February 1, 2014
• Primary Completion: July 1, 2016
• Study Completion: November 1, 2016
• Last Updated: November 22, 2016

Record last verified: 2016-11

Locations

BR (1)