Virtual Neuro-Navigation System for Personalized Community Based TMS

Study Overview
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Brief Summary
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Phase I study of a virtual neuro-navigation package with built-in support for identifying specific surface-based targets to optimze TMS treatment.

Detailed Description
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Background: Personalized MR neuro-navigation-based targeting approaches have been developed that have the potential to greatly increase TMS efficacy. Nevertheless, these have yet to be incorporated into routine clinical practice because of issues related to 1) the feasibility of neuro-navigation when applied to routine clinical practice, and 2) lack of biomarker-based validation of the critical target across individuals. Recent research at CU has begun to address both feasibility and targeting issues. In the MR-guided neuro-navigation approach, either structural or functional brain scans are used to identify a specific region of interest and the neuro-navigation system is then used to position the TMS coil to target that specific region across individuals. While this approach can be applied within specialized treatment settings, use of these devices requires expertise in 3D brain reconstruction that the majority of TMS providers do not possess. At CU, an initiative is underway to develop a virtual neuro-navigation system in which MRI images of the head and brain are uploaded into a server and neuro-navigation is performed in silico rather than in person. Scalp coordinates are then relayed to the clinician. Study: Under this phase I study, Soterix Medical would develop an initial version of the software (TMSMap) and CU would perform feasibility testing on patients with treatment resistant depression

Official Title
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Virtual Neuro-Navigation System for Personalized Community Based TMS

Conditions
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Treatment Resistant Depression

Intervention / Treatment
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* Device: Neuro-navigated Transcranial Magnetic Stimulation (TMS)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: DSM-5 diagnosis of major depressive disorder confirmed using the Mini International Neuropsychiatric Interview (MINI30) Axis 1 and mood modules Met criteria for treatment-resistant MDD during the current major depressive episode documented in the MGH Antidepressant Treatment History Questionnaire (ATRQ31), which will be defined as being non-responders (less than 50% of symptom improvement) to two or more depression treatment trials of adequate dose and duration as defined by the MGH ATRQ, as well as an adequate course of TMS treatment using standard targeting approaches (e.g. 5-cm, 5.5-cm, F3) at least moderate depression severity, operationalized as Montgomery-Asberg Depression Rating Scale (MADRS) score ≥ 20 Exclusion Criteria: Ever met criteria for a psychotic disorder (Sz, SzAff, Bipolar disorder), anorexia nervosa or bulimia nervosa within the last year Unstable medical condition by history, physical exam or laboratory results Currently pregnant or breastfeeding women; fecund women not using adequate contraceptive methods or with plan to become pregnant Contraindications to MRI (based on metal screening form) Meets criteria for claustrophobia Recent drug or alcohol use disorder with DSM-5 specifier of moderate or severe within 6 months, or mild within 2 months; lifetime history of IV drug use Actively suicidal, as defined by expressive ideation with a plan or with suicidal ideation that requires immediate medical or treatment intervention. A neurological or neuromuscular disorder Requires medications for a general medical condition that contraindicate the TMS treatment Prior non-response to ECT, vagal nerve stimulation (VNS) or deep brain stimulation (DBS) History of ketamine treatment within 6 mo History of monoamine oxidase inhibitor (MAOI) within the past month Lacks capacity to consent Taking medications that increase the risk of seizures. For patients on permitted concomitant psychotropic agents (antidepressants, anticonvulsants, benzodiazepines, hypnotics, opiates, triiodothyronine (T3), modafinil, psychostimulants, buspirone, melatonin, omega-3 fatty acids, folate, l-methylfolate, s-adenosyl methionine, lithium) dosing must be stable for at least four weeks prior to study entry and patients must agree to continue at the same dose during the study

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 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: Non-Randomized
Intervention Model: Sequential Assignment
Interventional Model Description: Phase I open-label, 12 subjects
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: virtual neuro-navigation<br>The specific area within the L-DLPFC will be identified by a software using MR images. TMS will be administered to the identified area. | Device: Neuro-navigated Transcranial Magnetic Stimulation (TMS)<br>* TMS delivered to a target within the left- dorsolateral prefrontal cortex (L-DLPFC)<br>* Other names: Transcranial Magnetic Stimulation;|
| Experimental: on-line neuro-navigation<br>The specific area within the L-DLPFC will be identified by a person using MR images. TMS will be administered to the identified area. | Device: Neuro-navigated Transcranial Magnetic Stimulation (TMS)<br>* TMS delivered to a target within the left- dorsolateral prefrontal cortex (L-DLPFC)<br>* Other names: Transcranial Magnetic Stimulation;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Montgomery-Asberg Depression Rating Scale (MADRS) | Depression severity scale where higher score indicates greater severity of symptoms | 2 times per week from Baseline until Week 6 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hamilton Depression Rating Scale Anxiety Somatization Subscale (HAMD-AS)33 | six-item subscale of psychiatric disorder severity where higher score indicates greater severity of symptoms | Baseline and at Week 6 | 
| Side-effect form (SEF) | clinician-rated simple form to document the onset, course, severity, and causality of adverse events | 2 times per week from Baseline until Week 6 | 
| Columbia suicide severity rating scale (C-SSRS) | FDA approved scale for assessment of suicidality | 2 times per week from Baseline until Week 6 | 
| Concomitant Medication List (CML) | This instrument will collect information on all concomitant medications | 2 times per week from Baseline until Week 6 |