Low Field Magnetic Stimulation for Treatment Resistant Depression

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.

Inclusion Criteria:

1. Subjects must be able to understand and read English and give written informed consent
prior to the protocol required procedures.

2. Men and women, ages 18 to 65 inclusive with a diagnosis of major depressive episode as
defined by DSM-IV-TR criteria.

3. History of an inadequate response to 1 or more adequate antidepressant treatments in
the current depressive episode.

4. Subjects must have a 17-item Hamilton Rating Scale for Depression (HAM-D-17) score ≥
18.

5. Subjects must have a Body Mass Index (BMI) of approximately 18-40 kg/m².

6. Women of childbearing potential (WOCBP) must be using an adequate method of
contraception to avoid pregnancy throughout the study and must have a negative urine
pregnancy test within 72 hours prior to the start of LFMS.

Exclusion Criteria:

1. WOCBP who are unwilling or unable to use an acceptable method to avoid pregnancy for
the entire study period.

2. Women who are pregnant or breastfeeding.

3. Subjects with other DSM-IV-TR Axis I disorders other than Generalized Anxiety Disorder
(GAD: 300.02), Social Anxiety Disorder (300.23), or Specific Phobia (300.29). Subjects
with co-morbid GAD, Social Anxiety Disorder, or Specific Phobia are ineligible if the
co-morbid condition is clinically unstable, requires treatment, or has been the
primary focus of treatment within the 6 month period prior to screening.

4. Delirium, dementia, or other cognitive disorder

5. Schizophrenia or other psychotic disorder, based on the MINI.

6. Patients with a clinically significant Axis II diagnosis of borderline, antisocial,
paranoid, schizoid, schizotypal or histrionic personality disorder.

7. Patients experiencing hallucinations, delusions, or any psychotic symptomatology in
the current or any previous depressive episode.

8. Patients who have met DSM-IV-TR criteria for any significant substance use disorder
within the past six months.

9. Patients receiving new-onset psychotherapy and/or somatic therapy (light therapy,
transcranial magnetic stimulation) within 6 weeks of screening, or at any time during
participation in the trial.

10. Patients who, in the opinion of the Investigator, are actively suicidal and at
significant risk for suicide.

11. Patients who have participated in any clinical trial with an investigational drug or
device within the past month.

12. Patients who have received ECT in the past 20 years or Vagal Nerve/Deep Brain
Stimulation during their lifetime.

13. Unstable medical illness including, cardiovascular, hepatic, renal, respiratory,
endocrine, neurological, or hematological disease.

14. Subjects with evidence or history of significant neurological disorder, including head
trauma with loss of consciousness, history of stroke, Parkinson's disease, epilepsy
disorder, conditions that lower seizure threshold, seizures of any etiology (including
substance or drug withdrawal), who are taking medications to control seizures, or who
have increased risk of seizures as evidenced by history of EEG with epileptiform
activity (with the exception of juvenile febrile seizures).

15. Patients with thyroid pathology (unless condition has been stabilized with medications
for at least the past three months).

16. Patients who have recently (within two weeks) begun any medications.

17. Monoamine oxidase inhibitors (e.g., Nardil, phenelzine, Parnate, tranylcypromine,
Marplan, isocarboxazide) treatment within the 2 weeks prior to enrollment.

18. Patients with a history of antidepressant-induced hypomania or dysphoria.

19. Participants with metal implants (Will use the NY Presbyterian Hospital MRI Checklist)

20. Any of the following exclusion criteria for MRI Cardiac pacemaker or pacing wires
Implanted cardioverter defibrillator (ICD) Cochlear, otologic, or other ear implant
Tissue expander (e.g., breast) Implanted drug infusion device Aneurysm clip(s) Deep
Brain Stimulator Other Neuro-stimulator Prosthesis (eye, penile, limb, etc.)
Artificial heart valve Eyelid spring or wire Stent, filter, or coil Programmable shunt
Catheter or feeding tube with metal tip Radiation seeds Medication patch (Nicotine,
Nitroglycerine) Any metallic fragment, foreign body or bullets Surgical staples,
clips, metallic sutures or wire mesh Bone/joint pin, screw, nail, wire, plate, etc.
IUD, diaphragm, or pessary Dentures or braces Tattoo, permanent makeup or body
piercing jewelry Hearing aid (Remove before entering the MR system room) Breathing
problem and motion disorder Claustrophobia Hair Extensions