Low Field Magnetic Stimulation for Treatment Resistant Depression

This is a double-blind, randomized, sham-controlled phase II study of the effects of Low Field Magnetic Stimulation (LFMS) on brain circuitry of adults with treatment-resistant Major Depressive Disorder (MDD). Eligible subjects will be randomly assigned to double-blind treatment with three 20 minute sessions of either (1) active LFMS or (2) sham LFMS. Resting state fMRI will be performed at baseline and following the third and final treatment session.

A minimum of 60 subjects will enter the double-blind treatment phase of the study. This trial will be conducted according to the U.S. Food and Drug Administration guidelines and the Declaration of Helsinki. Written informed consent will be obtained from all patients before protocol-specified procedures are carried out. The subjects will be drawn from an outpatient sample of patients with current Major Depressive Disorder (MDD) diagnosed with the use of the Mini International Neuropsychiatric Interview (MINI). LFMS will follow a previously published protocol for the treatment of a Major Depressive Episode (Rohan et al. 2004). LFMS treatments will be delivered with a prototype LFMS device manufactured by Tal Medical. LFMS sessions consist of proton echo-planar magnetic resonance spectroscopic imaging (EP-MRSI) and will be 20min in duration. LFMS exposes subjects to magnetic fields of the same magnitude and frequency used in clinical MR-Spectroscopic imaging of the brain. Sham LFMS will consist of a three-dimensional spoiled gradient echo sequence of the same duration as active LFMS and which provides auditory stimulation indistinguishable from active treatment. At the beginning of a treatment session, the subject will sit in front of and position his head within the open bore of the Tal Medical LFMS device. The device will be pre-programmed to deliver active or sham treatment so that the subject, operator, and all investigators are blinded to active treatment vs. sham. Immediately before and after each treatment session, the PANAS, Ham-D-6, and Visual Analog Mood Scale will be administered and the patient will be monitored for any adverse events. All participants will undergo two sessions of neuroimaging: On the Friday prior to the first treatment session (Day 0) and on the day of the third and final treatment session (Day 7). Each session of neuroimaging will be 50 minutes in duration and include three imaging modalities: Resting State fMRI (rsfMRI), Arterial Spin Labeling MRI (ASL), and Diffusion Tensor Imaging (DTI). In addition, we will obtain high-resolution anatomical volumes (SPGR) for each subject for the purpose of transforming each individual's imaging data into a common space for group comparisons. Subjects will lie still in the scanner and will be instructed to let their mind "wander freely" during the acquisition of the resting state fMRI scan, which will last 6 minutes (Anon 2001). They will also be instructed to lie still during the ASL and DTI scans (each lasting 8 minutes). In addition, we will obtain a high-resolution T1-weighted (MP-RAGE) anatomical scan for co-registration of each individual's imaging data into a common space for group statistics.. Resting state fMRI will be used to measure the functional connectivity within the default mode network (DMN) and other circuits that are known to function abnormally in MDD (Greicius et al. 2007). ASL will be used to measure the regional blood flow within individual nodes of this circuitry, while DTI will measure the structural integrity of the connections between nodes. Measurements at baseline will be compared to measurements post-LFMS in both active treatment and sham groups.