Stanford Accelerated Intelligent Neuromodulation Therapy for Treatment-Resistant Depression: OL Cohort

Study Overview
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Brief Summary
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This study evaluates an accelerated schedule of theta-burst stimulation using a transcranial magnetic stimulation device for treatment-resistant depression. In this open label study, all participants will receive accelerated theta-burst stimulation.

Detailed Description
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Repetitive transcranial magnetic stimulation (rTMS) is an established technology as therapy for treatment-resistant depression. The approved method for treatment is 10Hz stimulation for 40 minutes over the left dorsolateral prefrontal cortex (L-DLPFC) for a 6 week treatment course. This methodology has been successful for many people with treatment-resistant depression. One of the limitations of this approach is the long duration of the treatment course (approximately a 6 weeks per treatment course). Recently, researchers have aggressively pursued modifying the treatment parameters to reduce treatment course time with some preliminary success. This study intends to further modify the parameters to create a more rapid form of the treatment. This study will also look at the change in neuroimaging biomarkers associated with this treatment.

Official Title
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Stanford Accelerated Intelligent Neuromodulation Therapy for Treatment-Resistant Depression (SAINT-TRD)

Conditions
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Treatment Resistant Depression

Intervention / Treatment
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* Device: Accelerated theta-burst stimulation treatment


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female, 22 to 80 years of age. Able to provide informed consent. Diagnosed with Major Depressive Disorder (MDD) and currently experiencing a Major Depressive Episode (MDE). Participants may currently be on a stable and adequate dose of an antidepressant therapy but the medication must remain stable throughout study enrollment. Participants may also have a history of intolerance to antidepressant medications. These patients with the intolerance history will not be required to be currently taking an antidepressant medication. Meet the threshold on the total HAMD17 score of >/=20 at both screening and baseline visits (Day -5/-14 and Day 0). Meet the threshold on the total MADRS score of >/=20 at both screening and baseline visits (Day -5/-14 and Day 0). Meet the threshold on the total BDI-II score of >/=20 at both screening and baseline visits (Day -5/-14 and Day 0). In good general health, as ascertained by medical history. If female, a status of non-childbearing potential or use of an acceptable form of birth control. Concurrent hypnotic therapy (e.g., with zolpidem, zaleplon, melatonin, or trazodone) will be allowed if the therapy has been stable for at least 4 weeks prior to screening and if it is expected to remain stable. History of ECT intolerance is permitted. Exclusion Criteria: Female of childbearing potential who is not willing to use one of the specified forms of birth control during the study. Female that is pregnant or breastfeeding. Total HAMD score of < 20 at the screen or baseline visits. Total MADRS score of < 20 at the screen or baseline visits. Total BDI-II score of < 20 at the screen or baseline visits. Current diagnosis of a Substance Use Disorder (Abuse or Dependence, as defined by DSM-IV-TR), with the exception of nicotine dependence. Current diagnosis of Axis I disorders other than Dysthymic Disorder, Generalized Anxiety Disorder, Social Anxiety Disorder, Panic Disorder, Agoraphobia, or Specific Phobia (unless one of these is comorbid and clinically unstable, and/or the focus of the participant's treatment for the past six months or more). History of schizophrenia or schizoaffective disorders, or any history of psychotic symptoms in the current or previous depressive episodes. Any Axis I or Axis II Disorder, which at screening is clinically predominant to their MDD or has been predominant to their MDD at any time within six months prior to screening. Has a clinically significant abnormality on the screening examination that might affect safety, study participation, or confound interpretation of study results. Participation in any clinical trial with an investigational drug or device within the past month or concurrent to study participation. Any current or past history of any physical condition which in the investigator's opinion might put the subject at risk or interfere with study results interpretation. Positive screening on the urine test for drugs of abuse at screening: cocaine, amphetamines, barbiturates, opiates. Current (or chronic) use of opiates. History of epilepsy. History of shrapnel or metal in the head or skull. History of cardiovascular disease or cardiac event. History of OCD. History of autism spectrum disorder. History of rTMS exposure

Ages Eligible for Study
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Minimum Age: 22 Years
Maximum Age: 80 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Accelerated theta burst treatment<br>All participants will receive theta-burst TMS. | Device: Accelerated theta-burst stimulation treatment<br>* All participants will receive intermittent theta-burst stimulation (iTBS) to the left dorsal lateral prefrontal cortex (L-DLPFC). The L-DLPFC will be targeted utilizing the Localite neuronavigation system. Stimulation intensity will be standardized at 90% of resting motor threshold (adjusted for cortical depth). Stimulation will be delivered to L-DLPFC using the Magventure Magpro X100 and/or the NextStim TMS system.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Change in the Montgomery Asberg Depression Rating Scale (MADRS) Score From Pre-treatment to 1-month | A ten item diagnostic questionnaire used to measure the severity of depressive symptoms in patients with mood disorders. Scale range - 0 to 60 with higher score indicative of greater depressive symptomology. | Pre-treatment and 1-month post treatment. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Change in the Columbia Suicide Severity Rating Scale (C-SSRS) | A suicidal ideation rating scale created by researchers at Columbia University. The score was calculated by summing the answers to 5 questions. Score range - 0 to 5. Higher score indicate higher suicidal ideation. | Pre-treatment to immediately post-treatment (on day 5) and 4 weeks post-treatment | 
| Percent Change in the Hamilton Rating Scale for Depression (HAM-6) | A 6 item questionnaire used to score the severity of depression. Scale range - 0 to 22 with higher score indicative of greater depressive symptomology. Additional collection time points were pre-specified; only those time points for which data were collected are reported. | Pre-treatment to immediately post-treatment (on day 5) and 2 weeks,4 weeks and 6 weeks post-treatment | 
| Percent Change in the Hamilton Rating Scale for Depression (HAM-17) | A provider administered questionnaire used to assess remission and recovery from depression. Scale range - 0 to 52 with higher score indicative of greater depressive symptomology. Additional collection time points were pre-specified; only those time points for which data were collected are reported. | Pre-treatment to immediately post-treatment (on day 5) and 2 weeks, 4 weeks, 6 weeks and 8 weeks post-treatment | 
| Change From Baseline Functional Connectivity to 1-month Post-treatment | We will assess change in resting state fMRI functional connectivity of the subcallosal cingulate to the default mode network and within the default mode network. | Pre-treatment, immediately post-treatment (on day 5), 1-month post-treatment | 
| Percent Change in the Beck Depression Inventory (BDI-II) | A 21 item Self-report measure of depressive symptoms. Scale range - 0 to 63 with higher score indicative of greater depressive symptomology. Additional collection time points were pre-specified; only those time points for which data were collected are reported. | Pretreatment to immediately post-treatment (on day 5) and 2 weeks, 4 weeks, 6 weeks and 8 weeks post treatment. | 
| Percent Change in the Montgomery Asberg Depression Rating Scale (MADRS) | A ten item diagnostic questionnaire used to measure the severity of depressive symptoms in patients with mood disorders. Scale range - 0 to 60 with higher score indicative of greater depressive symptomology. Additional collection time points were pre-specified; only those time points for which data were collected are reported. | Pre-treatment to immediately post treatment (on day 5) and 2 weeks, 4 weeks and 8 weeks post-treatment | 
| Change From Baseline Functional Connectivity to Immediately Post-treatment | Within subject changes in resting state functional connectivity of subgenual anterior cingulate cortex (sgACC) to default mode network (DMN). frontal (f)DMN (medial prefrontal cortex), median (m)DMN (posterior cingulate cortex and precuneus), left (l)DMN (left angular gyrus), right (r)DMN (right angular gyrus). T-statistic (T-score): ratio of departure of estimated value from its hypothesized value to its standard error used in a t-test to determine whether to support or reject the null hypothesis. A T-score of ≥ 2.11 or ≤ -2.11 would be considered a statistically significant change if the accompanying p-value (subject to false discovery rate correction of multiple comparisons) was ≤ 0.05. Positive T-score = increased connectivity, negative T-score = decreased connectivity. No established reference range or clinically meaningful threshold exists for this patient population. Higher connectivity between all DMN nodes to sgACC has been found in depressed vs healthy population. | Pre-treatment to immediately post treatment (on day 5). | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Major Depressive Disorder, Treatment-Resistant Depression, Transcranial Magnetic Stimulation (TMS), Theta-Burst Stimulation