Accelerated Intermittent Theta Burst Stimulation for Inpatients With Major Depressive Disorder (aiTBS)

Sponsor:

Collaborators:

Information provided by (Responsible Party):

Nolan R，Stanford University

Tracking Information

First Submitted Date ^ICMJE

September 27, 2018

First Posted Date ^ICMJE

October 2, 2018

Last Update Posted Date

October 2, 2018

Actual Study Start Date ^ICMJE

October 2018

Estimated Primary Completion Date

October 2019 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures ^ICMJE

Change in Hamilton Rating Scale for Depression Six Item (HAMD-6) score[ Time Frame: After all stimulation sessions have been completed (approximately 48 hours after the final session) ]

Clinical assessment measuring depressive symptoms. Scores range from 0-24 with scores >5 indicating clinical levels of depressive symptoms.

Original Primary Outcome Measures ^ICMJE

Same as current

Current Secondary Outcome Measures ^ICMJE

Change in Montgomery Asberg Depression Rating Scale (MADRS) score[ Time Frame: After all stimulation sessions have been completed (approximately 48 hours after the final session) ]
A 10-item clinician-administered scale, designed to be particularly sensitive to antidepressant treatment effects in patients with major depression. Severity gradations for the MADRS have been proposed: 9-17 = mild depression, 18-34 = moderate depression, and ≥ 35 = severe depression. Scores range from 0-60.
Change in Scale of Suicidal Ideation (SSI) score[ Time Frame: After all stimulation sessions have been completed (approximately 48 hours after the final session) ]
19-item clinician administered assessment to measure the intensity, pervasiveness, and characteristics of suicidal ideation in adults. Scores range from 0-38.
Change in resting-state recordings and TMS-evoked potentials in EEG data.[ Time Frame: After all stimulation sessions have been completed (approximately 48 hours after the final session) ]
For the first and last stimulation session, EEG recording will be made before (resting-state EEG) and during (TMS-evoked potentials) the stimulation.
Change in Quick Inventory Depressive Scale-Self Reported (QIDS) score[ Time Frame: After all stimulation sessions have been completed (approximately 48 hours after the final session) ]
Self-report measure of depressive symptoms. The questionnaire consists of 16 questions. Each question can score between 0 to 4 points. Severity of depression is determined as follows: 0=None, 1=Mild, 2=Moderate, 3=Severe, 4=Very Severe. Total scores range from 0-27. Total scores: 0-5= no depression, 6-10= mild depression, 11-15= moderate depression, 16-20= severe depression, 21-27= very severe depression. The total score is obtained by adding the scores for each of the nine symptom domains of the DSM-IV MDD criteria: depressed mood, loss of interest or pleasure, concentration/decision making, self-outlook, suicidal ideation, energy/fatigability, sleep, weight/appetite change, and psychomotor changes (Rush et al. 2003).
Change in Pittsburgh Insomnia Rating Scale-20 Item Version (PIRS-20) score[ Time Frame: After all stimulation sessions have been completed (approximately 48 hours after the final session) ]
Self-report, 20 item scale to determine patient's insomnia level. Each question can be scored between 0-3. 0=not bothered at all slightly bothered moderately bothered severely bothered Total score is calculated by adding up all questions (i.e. Q1+Q2+...Q20). One missing item is allowed, pro-rate if missing one item....i.e. (sum/count)*20. Minimum Score = 0 (good); Maximum Score = 60 (bad)
Change in performance on the NIH toolbox[ Time Frame: After all stimulation sessions have been completed (approximately 48 hours after the final session) ]
Neurocognitive assessments delivered through an iPad app
Biomarker analysis in patient blood (plasma) samples[ Time Frame: After all stimulation sessions have been completed (approximately 48 hours after the final session) ]
Blood (plasma) samples will be collected before and one month after stimulation. Blood collection is conducted by the registered hospital phlebotomist (following same protocol of a routine blood test). Blood samples will be analyzed by our collaborators at the Open Medicine Institute. Specifically, samples will be used for DNA/RNA extraction and analyses will be done to determine potential gene targets. Presence of inflammatory markers (cytokines) will also be determined. All analyses of blood samples will be conducted in the Open Medicine Institute.
Biomarker analysis in patient stool samples[ Time Frame: After all stimulation sessions have been completed (approximately 48 hours after the final session) ]
Stool samples will be collected before and one month after stimulation. Stool collection is performed by registered hospital nurses. Stool samples will be analyzed by our collaborators at the Open Medicine Institute. Specifically, stool samples will be analyzed for potential biomarkers in the gut microbiome. All analyses of stool samples will be conducted in the Open Medicine Institute.
Biomarker analysis in patient saliva samples[ Time Frame: After all stimulation sessions have been completed (approximately 48 hours after the final session) ]
Saliva samples will be collected before and one month after stimulation. Saliva collection is performed by registered study personnel. Saliva samples will be analyzed by our collaborators at the Open Medicine Institute. Specifically, saliva samples will be analyzed for cortisol levels. All analyses of stool samples will be conducted in the Open Medicine Institute.
Change in Bush-Francis Catatonia Rating Scale (BFCRS).[ Time Frame: After all stimulation sessions have been completed (approximately 48 hours after the final session) ]
A clinician administered assessment of catatonia. The Bush-Francis Catatonia Rating Scale (BFCRS) is a standardized, quantifiable examination of catatonia designed to screen and diagnose the possibility of catatonia. The BFCRS consists of a 23-item rating scale with the first 14 items comprising the Bush Francis Catatonia Screening Instrument (BFCSI). For screening, items 1-14 are marked as absent (0) or present (3). The presence of two or more of the screening items for 24 hours or longer meets the diagnosis for catatonia proposed by Bush et al. For severity, items 1-23 are rated using a scale of 0-3. The total BFCRS score is the sum of responses to all 23 items.
Change in the Quality of Life Enjoyment and Satisfaction Questionnaire-short form score (Q-LES-Q-SF)[ Time Frame: After all stimulation sessions have been completed (approximately 48 hours after the final session) ]
15-item self-report questionnaire where each item is scored from very poor=1 to very good=5. The scoring of the Q-LES-Q-SF involves summing only the first 14 items to yield a raw total score. The last two items are not included in the total score but are stand-alone items. The raw total score ranges from 14 (min) to 70 (max).
Change in Immediate Mood Scaler (Ims-12) score[ Time Frame: After all stimulation sessions have been completed (approximately 48 hours after the final session) ]
Immediate Mood Scaler (IMS) is a newly developed, iPad-deliverable 12-item self-report tool designed to capture current mood states. Scores range from bad=0 to good=7, for each item.
Change in Columbia Suicide Severity Rating Scale (C-CSSRS)[ Time Frame: After all stimulation sessions have been completed (approximately 48 hours after the final session) ]
A trained rater will administer the Columbia Suicide Severity Rating Scale (C-CSSRS). This questionnaire was developed to rate suicidal ideation and behavior. It rates a person's degree of suicidal ideation on a scale, ranging from "wish to be dead" to "active suicidal ideation with specific plan and intent and behaviors. The scale identifies specific behaviors which may be indicative of a person's intent to complete suicide. An person exhibiting even a single behavior identified by the scale was 8 to 10 times more likely to complete suicide.
Change in heart rate[ Time Frame: After all stimulation sessions have been completed (approximately 48 hours after the final session) ]
Measure presence of any change in heart rate variability
Change in Temporal Experience of Pleasure Scale (TEPS)[ Time Frame: After all stimulation sessions have been completed (approximately 48 hours after the final session) ]
The Temporal Experience of Pleasure Scale (TEPS) is a measure specifically designed to capture the anticipatory and consummatory facets of pleasure. TEPS is an 18-item questionnaire. Each item is scored from 0 "very false for me" to 6 "very true for me". Total score ranges from 0 to 108.

Descriptive Information

Brief Title ^ICMJE

Accelerated Intermittent Theta Burst Stimulation for Inpatients With Major Depressive Disorder (aiTBS)

Official Title ^ICMJE

Accelerated Intermittent Theta Burst Stimulation for Inpatients With Major Depressive Disorder

Brief Summary

This study evaluates an accelerated schedule of theta-burst stimulation for inpatients with major depressive disorder

Detailed Description

This study intends to investigate whether modifying stimulation parameters enables typical 6-8 week long rTMS protocols to be compressed to only five days. The influence of this accelerated protocol on the length of patient stay in the hospital and the direct total cost will be investigated.

Study Type ^ICMJE

Interventional

Study Phase

N/A

Study Design ^ICMJE

Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Patients will receive stimulation to one of two brain areas. Patients will be randomized to either stimulation site.
Masking: Interventional
Masking Description:
Primary Purpose: Treatment

Condition ^ICMJE

Intervention ^ICMJE

Device: Accelerated theta burst stimulation
All participants will receive iTBS (intermittent theta burst stimulation), either to the left DLPFC or ACC. Stimulation intensity will be individualized according to the individual's resting motor threshold.

Study Arms

Active Comparator: Dorsolateral prefrontal cortex
The accelerated theta burst stimulation protocol will be applied to the dorsolateral prefrontal cortex (dlPFC)
Active Comparator: Anterior cingulate cortex
The accelerated theta burst stimulation protocol will be applied to the anterior cingulate cortex (ACC)

Recruitment Information

Recruitment Status ^ICMJE

Not yet recruiting

Estimated Enrollment ^ICMJE

100

Original Estimated Enrollment ^ICMJE

Same as current

Estimated Study Completion Date

October 2020

Estimated Primary Completion Date

October 2019 (Final data collection date for primary outcome measure)

Eligibility Criteria ^ICMJE

Inclusion Criteria: - Admitted to the psychiatric inpatient unit with a diagnosis of MDD and displaying suicidal ideation [elevated scores on the scale of suicidal ideation (SSI; scores of 5 or more)] - Motor threshold value which enables treatment. - Qualifies and has access to outpatient rTMS treatment - If older than 70, MRI needs to be analyzed to confirm eligibility-no atrophy or lesions etc Exclusion Criteria: - Primary diagnosis other than MDD. - Any structural neurological condition - Metal implant in brain (e.g. deep brain stimulation), cardiac pacemaker, or cochlear - History of epilepsy/ seizures (including history of withdrawal/ provoked seizures) - Pregnancy - Autism Spectrum disorder - Active substance use (<1 week) or intoxication verified by toxicology screen--of cocaine, amphetamines, benzodiazepines - Cognitive impairment (including dementia) - Current severe insomnia (must sleep a minimum of 5 hours the night before stimulation) - Current mania - Current unmanageable psychosis - IQ <70 - Any other indication the PI feels would comprise data. - Undetermined parkinsonism or Parkinson's patients who are not taking levodopa. - More subcortical lesions than would be expected for age or a stroke effecting stimulated area or connected areas.

Sex/Gender

Sexes Eligible for Study:

All

Ages

18 Years and older (Adult, Older Adult)

Accepts Healthy Volunteers

Listed Location Countries ^ICMJE

United States

Removed Location Countries

Administrative Information

Has Data Monitoring Committee

U.S. FDA-regulated Product

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: Yes

IPD Sharing Statement

Plan to Share IPD:

Responsible Party

Nolan R，Stanford University

Study Sponsor ^ICMJE

Stanford University

Collaborators ^ICMJE

Investigators ^ICMJE

Principal Investigator: Nolan Williams, MD Stanford University
Study Director: Eleanor Cole, PhD Stanford University

PRS Account

Stanford University

Verification Date

October 2018

^ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP

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