Multiple Treatment Study Using Low Field Magnetic Stimulation for Bipolar Depression

Study Overview
=================
Brief Summary
-----------------
Objectives: To demonstrate the duration of the antidepressant effect of Low Field Magnetic Stimulation (LFMS)in subjects with bipolar depression. Hypotheses: Investigators expect subjects who receive LFMS to show significant mood improvement one week after the start of a three day course of daily stimulation as compared to subjects who receive sham LFMS. Investigators expect subjects who receive LFMS to show immediate mood improvement over the first treatment as measured by the difference in pre and post-treatment PANAS+ ratings. Investigators expect to show that LFMS will be well tolerated in a three-treatment protocol.

Detailed Description
-----------------
Low Field Magnetic Stimulation is an electromagnetic intervention being investigated at McLean Hospital because of its effect on symptoms of depression. It consists of pulsed electric fields that are induced remotely in the head by a portable coil. It has been observed to have mood elevating effects in depressed patients with Bipolar Disorder (BPD). These effects are immediate, occurring upon completion of a 20 minute treatment. LFMS is unique because of its low electric field strength, and because of its high frequency operation, compared to other electromagnetic treatments. While other treatments such as Electroconvulsive Therapy (ECT) use electric fields equivalent to > 100-200 Volts/meter to affect the brain, LFMS uses <1 V/m. Such a low electric field strength indicates that another mechanism is activated by LFMS, and this provides a possibility for a new treatment. It may also give insight into causes of depression. LFMS is also unique because it has an immediate effect. This immediate effect may have implications for emergency treatment. The purpose of this study is to observe the response to LFMS in depressed BPD subjects with the aim of assessing the effects of multiple treatments, and of observing the duration of the mood improvement.To do so, the investigators propose to study 72 subjects in a protocol of three treatments in three days. Subjects will be rated before and after each treatment, and will return for mood ratings at one week after treatment. Investigators hope that this characterization of LFMS will allow clinical research groups to perform large trials and to evaluate its clinical effectiveness in patient populations.

Official Title
-----------------
Low Field Magnetic Stimulation in Mood Disorders: Three Daily Visits

Conditions
-----------------
Bipolar Depression

Intervention / Treatment
-----------------
* Device: Low Field Magnetic Stimulation


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Subjects will be men or women between the ages of 21-65. Subjects must not have serious physical illnesses, neurological diseases or dementias. Subjects will meet DSM-IV criteria for Bipolar Disorder Type I or II and meet criteria for current depression (DSM-IV major depressive episode, current). Subject must have a MADRS >= 20, Young Mania Rating Score (YMRS score) < 7. Subjects must be capable of providing informed consent. Subjects must have an established residence and phone. Subjects may be medicated or unmedicated. Exclusion Criteria: Dangerous or active suicidal ideation. Pregnant or planning on becoming pregnant. Substance abuse (cannot meet DSM criteria for substance abuse, no significant drug abuse within last 3 months, no major polysubstance abuse history, no history of dependence in last year, no drug use within last month). Mania, hypomania or mixed mood state. Significant medical or neurological illness that might pose a risk to study enrollment or interfere with interpretation of study data. Changes in psychiatric medication (e.g. dose or drug) within 6 weeks prior to enrollment. History of schizophrenia, schizoaffective, obsessive-compulsive or post-traumatic stress disorders. Treatment resistant depression (as determined by the study psychiatrist; consistently and substantially symptomatic over several years despite electroconvulsive therapy, 2 or more adequate trials of a primary mood stabilizer with antidepressant effects (e.g., lithium, valproate or lamotrigine) or antidepressant medications (e.g., bupropion, Selective Serotonin Reuptake Inhibitors (SSRI) or Serotonin Norepinephrine Reuptake Inhibitor (SNRI).) Contraindications for Magnetic Resonance Imaging (MRI): Presence of a pacemaker, neurostimulator, or metal in head or neck.

Ages Eligible for Study
-----------------
Minimum Age: 21 Years
Maximum Age: 65 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: LFMS - active treatment<br>Low Field Magnetic Stimulation (LFMS) active treatment Active low field magnetic stimulation treatment applied with the LFMS Device; the device is on and magnetic field stimulation is present. | Device: Low Field Magnetic Stimulation<br>* Low Field Magnetic Stimulation is an electromagnetic technique. It uses low strength electric fields operating at a high frequency.<br>* Other names: LFMS;|
| Sham Comparator: LFMS - sham treatment<br>Low Field Magnetic Stimulation - sham treatment Inactive low field magnetic stimulation (no stimulation) treatment applied with the LFMS Device; the device is on, however no magnetic field stimulation is present. | Device: Low Field Magnetic Stimulation<br>* Low Field Magnetic Stimulation is an electromagnetic technique. It uses low strength electric fields operating at a high frequency.<br>* Other names: LFMS;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Long Term Change: Montgomery-Åsberg Depression Rating Scale (MADRS) | The Montgomery-Asberg Depression Rating scale assesses 10 symptom areas of depression during an interview. Each of the 10 items received a score ranging from 0 to 6. The scale has a range of 0-60 for the reported total. A higher score indicates increased depression for all items and for the total. This outcome measure is the change from pretreatment baseline acquired at the screening visit to a follow-up visit 7 days after the first treatment. | Variable based on screening visit schedule, > 2 weeks. | 
| Change Over First Treatment: Positive and Negative Affect Schedule (PANAS) Positive Items Subscale | PANAS consists of 10 positive and 10 negative valence word items. Items are rated by the participant to indicate their assessment of how they are feeling about this item right now on a scale of 1(slightly) or not at all through 5 (extremely). 10 of of the items form a positive affect subscale, in which a higher score indicates increased positive affect, with a subscale range of 10 to 50. 10 of the items form a negative affect subscale, in which a higher score indicates more negative affect, with a subscale range of 10 to 50. This outcome measure is change in the 10 item positive affect subscale. This outcome measure is the difference between the scale administered immediately (<30min) prior to the first treatment and immediately after (<30min) the first treatment. | 90 minutes; change immediately (<30min) prior to the first treatment and immediately after (<30min) the first treatment. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of of Change in Daily Improvement Over 3 Treatments: Positive and Negative Affect Schedule (PANAS) Positive Items Subscale | PANAS consists of 10 positive and 10 negative valence word items. Items are rated by the participant to indicate their assessment of how they are feeling about this item right now on a scale of 1(slightly) or not at all through 5 (extremely). 10 of of the items form a positive affect subscale, in which a higher score indicates increased positive affect, with a subscale range of 10 to 50. 10 of the items form a negative affect subscale, in which a higher score indicates more negative affect, with a subscale range of 10 to 50. This outcome measure uses the 10 item positive affect subscale. This outcome measure is the least squares fit of a linear coefficient to the three post (<30min oost treatment) minus pre (<30min pre treatment) score differences for the three treatment days | Over 3 days of treatment | 
| Rate of Change Over 3 Treatments: Montgomery-Asberg Depression Rating Scale (MADRS) | The Montgomery-Asberg Depression Rating scale assesses 10 symptom areas of depression during an interview. Each of the 10 items received a score ranging from 0 to 6. The scale has a range of 0-60 for the reported total. A higher score indicates increased depression for all items and for the total. This outcome measure is the least squares fit of a linear coefficient to the three pretreatment scores for the three treatment days | Over 3 days of treatment | 
| Rate of Change Over 3 Treatments: Positive and Negative Affect Schedule (PANAS) Positive Items Subscale | PANAS consists of 10 positive and 10 negative valence word items. Items are rated by the participant to indicate their assessment of how they are feeling about this item right now on a scale of 1(slightly) or not at all through 5 (extremely). 10 of of the items form a positive affect subscale, in which a higher score indicates increased positive affect, with a subscale range of 10 to 50. 10 of the items form a negative affect subscale, in which a higher score indicates more negative affect, with a subscale range of 10 to 50. This outcome measure uses the 10 item positive affect subscale. This outcome measure is the least squares fit of a linear coefficient to the three pretreatment scores for the three treatment days | Over 3 days of treatment | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Low Field Magnetic Stimulation, bipolar, depression, alternative treatment