Trial Outcomes & Findings for Stanford Accelerated Intelligent Neuromodulation Therapy for Treatment-Resistant Depression: OL Cohort (NCT NCT03240692)

Results Overview

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.

Recruitment status

COMPLETED

Study phase

NA

Target enrollment

23 participants

Primary outcome timeframe

Pre-treatment and 1-month post treatment.

Results posted on

2022-04-21

Participant Flow

Participant milestones

Participant milestones
Measure	Accelerated Theta Burst Treatment All participants will receive theta-burst TMS. Accelerated theta-burst stimulation treatment: 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.
Overall Study STARTED	23
Overall Study COMPLETED	21
Overall Study NOT COMPLETED	2

Reasons for withdrawal

Reasons for withdrawal
Measure	Accelerated Theta Burst Treatment All participants will receive theta-burst TMS. Accelerated theta-burst stimulation treatment: 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.
Overall Study Physician Decision	1
Overall Study Withdrawal by Subject	1

Baseline Characteristics

Race and Ethnicity were not collected from any participant.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Accelerated Theta Burst Treatment n=21 Participants All participants will receive theta-burst TMS. Accelerated theta-burst stimulation treatment: 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.
Age, Categorical <=18 years	0 Participants n=21 Participants
Age, Categorical Between 18 and 65 years	17 Participants n=21 Participants
Age, Categorical >=65 years	4 Participants n=21 Participants
Age, Continuous	44.86 years STANDARD_DEVIATION 17.21 • n=21 Participants
Sex: Female, Male Female	12 Participants n=21 Participants
Sex: Female, Male Male	9 Participants n=21 Participants
Region of Enrollment United States	21 Participants n=21 Participants
Montgomery Asberg Depression Rating Scale (MADRS) Score	34.86 Scores on a scale. STANDARD_DEVIATION 5.29 • n=21 Participants
Columbia Suicide Severity Rating Scale (C-SSRS)	1.42 Scores on a scale. STANDARD_DEVIATION 0.96 • n=19 Participants • Participants who provided data are included in the analysis.
Hamilton Rating Scale for Depression (HAM-6)	13.90 Scores on a scale. STANDARD_DEVIATION 2.45 • n=21 Participants
Hamilton Rating Scale for Depression (HAM-17)	25.90 Scores on a scale. STANDARD_DEVIATION 4.79 • n=21 Participants
Beck Depression Inventory (BDI-II)	28.78 Scores on a scale. STANDARD_DEVIATION 11.68 • n=18 Participants • Participants who provided data are included in the analysis.

PRIMARY outcome

Timeframe: Pre-treatment and 1-month post treatment.

Population: Participants who completed the protocol are included in the analysis.

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.

Outcome measures

Outcome measures
Measure	Accelerated Theta Burst Treatment n=21 Participants All participants will receive theta-burst TMS. Accelerated theta-burst stimulation treatment: 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.
Percent Change in the Montgomery Asberg Depression Rating Scale (MADRS) Score From Pre-treatment to 1-month	-67.07 Percentage of change in score Standard Deviation 34.71

SECONDARY outcome

Timeframe: Pre-treatment to immediately post-treatment (on day 5) and 4 weeks post-treatment

Population: Participants who provided data for the respective time point are included in the analysis.

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.

Outcome measures

Outcome measures
Measure	Accelerated Theta Burst Treatment n=19 Participants All participants will receive theta-burst TMS. Accelerated theta-burst stimulation treatment: 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.
Percent Change in the Columbia Suicide Severity Rating Scale (C-SSRS) Immediately post-treatment	-100 Percentage of change in score Standard Deviation 0
Percent Change in the Columbia Suicide Severity Rating Scale (C-SSRS) 4 weeks post-treatment	-100 Percentage of change in score Standard Deviation 0

SECONDARY outcome

Timeframe: Pre-treatment to immediately post-treatment (on day 5) and 2 weeks,4 weeks and 6 weeks post-treatment

Population: Participants who provided data for the respective time point are included in the analysis.

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.

Outcome measures

Outcome measures
Measure	Accelerated Theta Burst Treatment n=21 Participants All participants will receive theta-burst TMS. Accelerated theta-burst stimulation treatment: 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.
Percent Change in the Hamilton Rating Scale for Depression (HAM-6) immediately post-treatment	-81.96 Percentage of change in score Standard Deviation 25.98
Percent Change in the Hamilton Rating Scale for Depression (HAM-6) Week 2	-71.94 Percentage of change in score Standard Deviation 37.96
Percent Change in the Hamilton Rating Scale for Depression (HAM-6) Week 4	-65.54 Percentage of change in score Standard Deviation 39.40
Percent Change in the Hamilton Rating Scale for Depression (HAM-6) Week 6	-87.5 Percentage of change in score Standard Deviation 0

SECONDARY outcome

Timeframe: Pre-treatment to immediately post-treatment (on day 5) and 2 weeks, 4 weeks, 6 weeks and 8 weeks post-treatment

Population: Participants who provided data for the respective time point are included in the analysis.

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.

Outcome measures

Outcome measures
Measure	Accelerated Theta Burst Treatment n=21 Participants All participants will receive theta-burst TMS. Accelerated theta-burst stimulation treatment: 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.
Percent Change in the Hamilton Rating Scale for Depression (HAM-17) immediately post-treatment	-81.12 Percentage of change in score Standard Deviation 23.04
Percent Change in the Hamilton Rating Scale for Depression (HAM-17) Week 2	-74.58 Percentage of change in score Standard Deviation 27.97
Percent Change in the Hamilton Rating Scale for Depression (HAM-17) Week 4	-68.25 Percentage of change in score Standard Deviation 32.54
Percent Change in the Hamilton Rating Scale for Depression (HAM-17) Week 6	-88.89 Percentage of change in score Standard Deviation 0
Percent Change in the Hamilton Rating Scale for Depression (HAM-17) Week 8	-93.52 Percentage of change in score Standard Deviation 4.1

SECONDARY outcome

Timeframe: Pre-treatment, immediately post-treatment (on day 5), 1-month post-treatment

Population: Data analysis was not possible due to missing data and poor image quality (unable to read)

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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Pretreatment to immediately post-treatment (on day 5) and 2 weeks, 4 weeks, 6 weeks and 8 weeks post treatment.

Population: Participants who provided data for the respective time point are included in the analysis.

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.

Outcome measures

Outcome measures
Measure	Accelerated Theta Burst Treatment n=18 Participants All participants will receive theta-burst TMS. Accelerated theta-burst stimulation treatment: 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.
Percent Change in the Beck Depression Inventory (BDI-II) Immediately post-treatment	-84.89 Percentage of change in score. Standard Deviation 15.36
Percent Change in the Beck Depression Inventory (BDI-II) Week 2	-65.32 Percentage of change in score. Standard Deviation 49.57
Percent Change in the Beck Depression Inventory (BDI-II) Week 4	-54.84 Percentage of change in score. Standard Deviation 46.85
Percent Change in the Beck Depression Inventory (BDI-II) Week 6	-90.74 Percentage of change in score. Standard Deviation 13.09
Percent Change in the Beck Depression Inventory (BDI-II) Week 8	-100 Percentage of change in score. Standard Deviation 0

SECONDARY outcome

Timeframe: Pre-treatment to immediately post treatment (on day 5) and 2 weeks, 4 weeks and 8 weeks post-treatment

Population: Participants who provided data for the respective time point are included in the analysis.

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.

Outcome measures

Outcome measures
Measure	Accelerated Theta Burst Treatment n=21 Participants All participants will receive theta-burst TMS. Accelerated theta-burst stimulation treatment: 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.
Percent Change in the Montgomery Asberg Depression Rating Scale (MADRS) Week 2	-78.17 Percentage of change in score. Standard Deviation 25.46
Percent Change in the Montgomery Asberg Depression Rating Scale (MADRS) immediately post treatment	-85.06 Percentage of change in score. Standard Deviation 19.98
Percent Change in the Montgomery Asberg Depression Rating Scale (MADRS) Week 4	-67.07 Percentage of change in score. Standard Deviation 37.74
Percent Change in the Montgomery Asberg Depression Rating Scale (MADRS) Week 8	-96.30 Percentage of change in score. Standard Deviation 5.24

SECONDARY outcome

Timeframe: Pre-treatment to immediately post treatment (on day 5).

Population: Participants who provided data for the respective time point are included in the analysis

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.

Outcome measures

Outcome measures
Measure	Accelerated Theta Burst Treatment n=18 Participants All participants will receive theta-burst TMS. Accelerated theta-burst stimulation treatment: 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.
Change From Baseline Functional Connectivity to Immediately Post-treatment sgACC-rDMN	-2.660 T-score
Change From Baseline Functional Connectivity to Immediately Post-treatment sgACC-fDMN	-2.335 T-score
Change From Baseline Functional Connectivity to Immediately Post-treatment sgACC-mDMN	-3.027 T-score
Change From Baseline Functional Connectivity to Immediately Post-treatment sgACC-lDMN	-2.106 T-score

OTHER_PRE_SPECIFIED outcome

Timeframe: Pre-treatment, immediately post-treatment (on day 5) and 4 weeks post-treatment

Population: Participants who provided data for the respective time point are included in the analysis.

The Hopkins Verbal Learning Test - Revised (HVLT-DR). Score range 0 to 72, higher score indicates better verbal learning. The Brief Visuospatial Memory Test - Revised (BVMT-DR). Score range 0 to 84, higher score indicates better visuospatial memory. Digit Span test and various tests from the Delis Kaplan Executive Function System (DKEFS) will be used to assess possible cognitive side-effects. Score range 0-36, higher score indicates better executive functions.

Outcome measures

Outcome measures
Measure	Accelerated Theta Burst Treatment n=17 Participants All participants will receive theta-burst TMS. Accelerated theta-burst stimulation treatment: 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.
A Neuropsychological Test Battery Testing Cognitive Abilities HVLT-DR_Pre-treatment	48.81 score on a scale Standard Deviation 6.94
A Neuropsychological Test Battery Testing Cognitive Abilities HVLT-DR_ immediately post-treatment	48.18 score on a scale Standard Deviation 9.23
A Neuropsychological Test Battery Testing Cognitive Abilities HVLT-DR_Week 4	49.77 score on a scale Standard Deviation 10.38
A Neuropsychological Test Battery Testing Cognitive Abilities BVMT-DR_Pre-treatment	51.06 score on a scale Standard Deviation 9.44
A Neuropsychological Test Battery Testing Cognitive Abilities BVMT-DR_ immediately post-treatment	54.35 score on a scale Standard Deviation 8.14
A Neuropsychological Test Battery Testing Cognitive Abilities BVMT-DR_Week 4	56.23 score on a scale Standard Deviation 11.02
A Neuropsychological Test Battery Testing Cognitive Abilities DKEFS_Pre-treatment	17.35 score on a scale Standard Deviation 4.20
A Neuropsychological Test Battery Testing Cognitive Abilities DKEFS_ immediately post-treatment	19.06 score on a scale Standard Deviation 4.13
A Neuropsychological Test Battery Testing Cognitive Abilities DKEFS_Week 4	19.15 score on a scale Standard Deviation 3.67

Adverse Events

Accelerated Theta Burst Treatment

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Dr. Nolan Williams

Stanford University

Phone: 650-800-6920

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place