LFMS: Initial Trial in Geriatric Bipolar Depression

Study Overview
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Brief Summary
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The primary aim of this study is to assess the efficacy of Low Field Magnetic Stimulation (LFMS) in treating symptoms of depression and anxiety in older adults suffering from bipolar depression. The investigators also aim to assess any cognitive benefits from regular LFMS treatments in older adults suffering from bipolar depression.

Detailed Description
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The investigators have previously observed mood improvement in participants with bipolar depression in a population aged 21-60. Here the investigators hope to extend these results to a similar but new population, geriatric bipolar depression (GPD). In addition to the evaluation of the effect of multiple treatments, as well as observation of the duration of the effect after a delay of one week in this population, the investigators will assess whether this population presents any noticeable difference in tolerance or effect. This study was completed in two phases; the design of the second phase was revised based on results from a related study (2012P002380). The first phase had a randomized, double-blind, sham-controlled crossover design. Subjects were distributed equally into two groups; one group received three active LFMS sessions during a first treatment week and three sham LFMS sessions during a second treatment week, while the second group received sham LFMS first and then active LFMS. Specifically, all subjects made a baseline visit during week 0 (visit 1, any day) where scales of depression (Montgomery-Asberg Rating Scale (MADRS)), anxiety (Hamilton Anxiety Rating Scale (HARS)), and positive affect (Positive and Negative Affect Schedule (PANAS)) were completed. Subjects returned during week 1 for three treatment visits (visits 2,3,4 any days) during which they received active or sham LFMS according to their order assignment. Subject returned for the same mood ratings during week 2 (visit 5, any day). Subjects returned during week 3 for three treatment visits and received the alternate treatment according to their order assignment (visits 6,7,8, any days). Finally, subjects returned week 4 for to receive the mood ratings (visit 9, any day). The MADRS, HARS, and PANAS scales completed during weeks 0, 2, and 4 were the outcome measures. Treatment order assignments were randomized and balanced within blocks of 10 via a random number generator. Following review of data from a different Low Field Magnetic Stimulation study (2012P002380), the study design was revised, and a second phase of this protocol resulted. This is a randomized, double-blind, sham-controlled study with a parallel design (subjects will either receive active treatment or sham treatment for all treatment sessions). Specifically, the MADRS, HARS, and PANAS were completed on baseline visit 1 (day 0, Friday); 5 treatment visits were made on days 3,4,5,6,7 (visits 2-6); a mood rating visit 7 was made on day 10. The MADRS, HARS, and PANAS scales completed during days 0 and 10 were the outcome measures. Treatment order assignments were randomized and balanced within blocks of 10 via a random number generator. The mechanisms of depression in a geriatric population may differ from those in a younger population. Brain structures and connectivity have changed, and there is the increased risk of comorbid diagnoses such as dementia that might confound treatment and assessment. In this study the investigators hope to extend the findings of LFMS in the general population to directly address the treatment of bipolar depression in a geriatric population.

Official Title
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Low Field Magnetic Stimulation: Initial Trial in Geriatric Bipolar Depression

Conditions
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Bipolar Depression Depressed Phase

Intervention / Treatment
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* Device: Active Low Field Magnetic Stimulation
* Device: Sham Low Field Magnetic Stimulation


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Subjects will be men or women aged 55 years or older. Subjects will have a diagnosis of Bipolar Disorder Type I or II, current episode depressed as measure by a MADRS ≥ 20. Subjects must have failed at least one FDA approved treatment for bipolar depression before enrolling in this study. Failed treatment is defined as 8 weeks of treatment at standard dose (Selective Serotonin Reuptake Inhibitors (SSRI) , Selective Norepinephrine Reuptake Inhibitors (SNRI), mood stabilizer, or typical or atypical antipsychotic). Subjects must be maintained on a stable dose of all psychotropic medications for a period of at least two weeks prior to screening. Subjects must be capable of providing informed consent. Exclusion criteria: Subjects meeting Diagnostic Statistical Manual-IV-TR (DSM-IV-TR) criteria for any Axis I disorder other than Bipolar Disorder or an anxiety disorder (eg. Major Depressive Disorder, dementia). Subject has an Mini Mental State Exam (MMSE) score ≤ 24. Subject is pregnant or plans on becoming pregnant. Subject has recent history (within 7 days of screening) of ECT or TMS treatment. Subject has recent history of substance abuse (cannot meet DSM-IV-TR criteria for substance abuse, no significant drug abuse within last 3 months, no history of dependence in last year, no drug use within last month, other than marijuana use). Subject has any contraindication for Magnetic Resonance Imaging (MRI) (i.e. Presence of a pacemaker, neurostimulator, or metal in head or neck).

Ages Eligible for Study
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Minimum Age: 55 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: There are two phases. The first, pilot phase was a randomized, double-blinded crossover design. Following review of data from a different Low Field Magnetic Stimulation study (2012P002380) that showed a large order effect from the crossover design, revision of study design was prompted. The study design for this second phase was a randomized, double-blinded sham-controlled parallel design.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Phase 1: Cross-Over, Active LFMS first<br>Phase 1 crossover: three 20 minute treatments of active low field magnetic stimulation, once per day for three consecutive days during week 1. Then repeat with three 20 minute treatments of sham LFMS, once per day for three consecutive days during week 3. | Device: Active Low Field Magnetic Stimulation<br>* Low Field Magnetic Stimulation is an electromagnetic treatment being investigated for its effects on mood. It uses magnetic fields that are a fraction of the strength but at a higher frequency than the electromagnetic fields used in transcranial magnetic stimulation (TMS) and electroconvulsive therapy (ECT)<br>* Other names: Active LFMS;|
| Sham Comparator: Phase 1: Cross-Over, Sham LFMS first<br>Phase 1 crossover: three 20 minute treatments of sham low field magnetic stimulation, once per day for three consecutive days during week 1. Then repeat with three 20 minute treatments of active LFMS, once per day for three consecutive days during week 3. | Device: Sham Low Field Magnetic Stimulation<br>* The sham treatment does not provide any electromagnetic stimulation. However, it is designed so that it cannot be differentiated from the active treatment by producing mimicking sounds.<br>* Other names: Sham LFMS;|
| Experimental: Phase 2: Parallel, Active LFMS<br>Phase 2 parallel: five 20-minute active low field magnetic stimulation treatments, once per day for five consecutive days during week 1. | Device: Active Low Field Magnetic Stimulation<br>* Low Field Magnetic Stimulation is an electromagnetic treatment being investigated for its effects on mood. It uses magnetic fields that are a fraction of the strength but at a higher frequency than the electromagnetic fields used in transcranial magnetic stimulation (TMS) and electroconvulsive therapy (ECT)<br>* Other names: Active LFMS;|
| Sham Comparator: Phase 2: Parallel, Sham LFMS<br>Phase 2 parallel: five 20-minute sham low field magnetic stimulation treatments, once per day for five consecutive days during week 1. | Device: Sham Low Field Magnetic Stimulation<br>* The sham treatment does not provide any electromagnetic stimulation. However, it is designed so that it cannot be differentiated from the active treatment by producing mimicking sounds.<br>* Other names: Sham LFMS;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Montgomery Asberg Depression Rating Scale (MADRS) | The Montgomery-Asberg Depression Rating Scale (MADRS) is a diagnostic assessment measuring the severity of depressive symptoms. It is a 10-item scale assessing all core symptoms of repression. Each item is scored on a 7-point scale, ranging from 0 (symptom not present) to 6 (symptom severely present). Thus, the total score range is 0-60, with higher scores indicating more depressive symptom endorsement. | Phase 1 cross-over: scores at base visit 1 (week 0), visit 5 (week 2), and visit 9 (week 4). Differences are between visits 5-1 and 9-5. Phase 2 parallel: scores at base visit 1 (day 0) and visit 7 (day 10). Differences are between visits 7-1. | 
| Change in Hamilton Anxiety Rating Scale (HARS) | The Hamilton Anxiety Rating Scale (HARS) assesses the severity of anxiety symptoms. It is a 14-item scale covering psychic and somatic anxiety. Each item is scored on a 5-point scale, ranging from 0 (not present) to 4 (severe). Thus, the total score range is 0-56, wither higher scores indicating higher anxiety severity. | Phase 1 cross-over: scores at base visit 1 (week 0), visit 5 (week 2), and visit 9 (week 4). Differences are between visits 5-1 and 9-5. Phase 2 parallel: scores at base visit 1 (day 0) and visit 7 (day 10). Differences are between visits 7-1. | 
| Change in Positive and Negative Affect Schedule (PANAS), Positive Sub Scale | The Positive and Negative Affect Schedule (PANAS) assesses the presence and severity of two factors: positive affect (PA), which indicates the extent that a person is experiencing high energy, enthusiastic, mood state, and negative affect (NA), which indicates the extent a person is experiencing an aversive mood state. The PANAS is a 20-item scale, with 10 items measured PA and 10 items measuring NA. Each item is scored on a 5-point scale ranging from 1 (very slightly or not at all) to 5 (extremely). Thus, the score range for PA is 10-50, and the score range for NA is 10-50, with higher scores indicated more endorsement of PA (more energy, concentration, and pleasure) or NA (more anger, disgust, contempt). This study reports data on the score ranges for the PA sub-scale. | Phase 1 cross-over: scores at base visit 1 (week 0), visit 5 (week 2), and visit 9 (week 4). Differences are between visits 5-1 and 9-5. Phase 2 parallel: scores at base visit 1 (day 0) and visit 7 (day 10). Differences are between visits 7-1. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Bipolar Depression, Geriatric, Low Field Magnetic Stimulation