A Randomized Sham-Controlled Study of H-Coil Repetitive Transcranial Magnetic Stimulation for Treatment-Resistant Late-Life Depression

Study Overview
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Brief Summary
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The purpose of the study is to explore the efficacy and safety of H-Coil rTMS in comparison to a sham H-Coil rTMS in older patients with treatment-resistant major depressive disorder.Subjects will be randomized to receive H1-Coil rTMS or sham H1-Coil rTMS. The acute treatment phase will last four weeks. Treatment is administered daily, 5 days per week (i.e., 20 treatments). Depressive symptoms will be assessed using the HDRS-24. If subjects achieve the pre-defined primary outcome criteria of remission (HDRS-24 score < 10 and 60% reduction in symptoms) they will continue with twice weekly treatment for two more weeks to ensure the durability of the remission. Subjects who do not achieve remission will exit the study after the acute treatment phase of four weeks. The blind will not be broken to subjects until the completion of the study

Conditions
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Depression

Intervention / Treatment
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* Device: H- Coil DTMS
* Device: Sham


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: are outpatients are voluntary and competent to consent to treatment have a Structured Clinical Interview for DSM-IV (SCID)103 confirmedn DSM-IV diagnosis of MDD, single or recurrent are between the ages of 60 and 85 have failed to achieve a clinical response to an adequate dose of an antidepressant based on an Antidepressant Treatment History Form (ATHF) score of > 3 in the current episode 104, 105 OR have been unable to tolerate at least 2 separate trials of antidepressants of inadequate dose and duration (ATHF 1 or 2) have a score > 22 on the HDRS-24 have had no increase or initiation of any psychotropic medication in the 4 weeks prior to screening able to adhere to the treatment schedule Pass the TMS safety screening questionnaire have normal thyroid functioning based on pre-study blood work. Exclusion Criteria: have a history of DSM-IV substance dependence or abuse within the last 3 months have a concomitant major unstable medical illness, cardiac pacemaker or implanted medication pump are acutely suicidal are pregnant have a lifetime SCID diagnosis of bipolar I or II disorder, schizophrenia, schizoaffective disorder, schizophreniform disorder, delusional disorder, or current psychotic symptoms have a SCID diagnosis of obsessive compulsive disorder, post-traumatic stress disorder (current or within the last year), anxiety disorder (generalized anxiety disorder, social anxiety disorder, panic disorder) assessed by a study investigator to be primary and causing greater impairment than MDD have a SCID diagnosis of any personality disorder and assessed by a study investigator to be primary and causing greater impairment than MDD have presumed or probable dementia, as defined by Mini Mental Status Exam (MMSE) < 26 and clinical evidence of dementia. Patients screened out due to possible dementia will be referred to the local memory clinic for evaluation to clarify the presence or absence of dementia have failed a course of ECT within the current depressive episode have received rTMS for any previous indication due to the potential compromise of subject blinding have any significant neurological disorder or insult including, but not limited to: any condition likely to be associated with increased intracranial pressure, space occupying brain lesion, any history of seizure except those therapeutically induced by ECT, cerebral aneurysm, Parkinson's disease, Huntington's chorea, multiple sclerosis, significant head trauma with loss of consciousness for greater than or equal to 5 minutes on a dose of Buproprion greater than 300mg per day have an intracranial implant (e.g., aneurysm clips, shunts, stimulators, cochlear implants, or electrodes) or any other metal object within or near the head, excluding the mouth, that cannot be safely removed if participating in psychotherapy, must have been in stable treatment for at least 3 months prior to entry into the study, with no anticipation of change in the frequency of therapeutic sessions, or the therapeutic focus over the duration of the study clinically significant laboratory abnormality, in the opinion of the investigator currently (or in the last 4 weeks) take more than lorazepam 2 mg daily (or equivalent) or any dose of an anticonvulsant due to the potential to limit rTMS efficacy inability to communicate non-correctable clinically significant sensory impairment (i.e., cannot hear well enough to cooperate with interview).

Ages Eligible for Study
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Minimum Age: 60 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
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: H coil DTMS<br>20 daily deep TMS treatments | Device: H- Coil DTMS<br>* 20 daily deep rTMS treatments<br>* Other names: H1 coil DTMS;|
| Sham Comparator: inactive stimulation<br>20 daily sham deep TMS treatments | Device: Sham<br> <br> * Other names: inactive treatment;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Improvement in depression symptoms, evaluated by HDRS | Clinical antidepressant response at the end of the treatment, define as a decline in Hamilton depression rating scale (HDRS-24) from the baseline rating by 50%. | 6-8 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 1. Remission in depression | 1. Clinical antidepressant remission at the end of the treatment, define as exit HDRS-24 <10 and 60% reduction in total score. | 6-8 weeks |