Accelerated Intermittent Theta Burst Stimulation for Depressive Symptoms (aTBS)
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| ClinicalTrials.gov Identifier: NCT03601117 |
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Recruitment Status :
Completed
First Posted : July 26, 2018
Results First Posted : August 10, 2021
Last Update Posted : August 10, 2021
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This study evaluates an accelerated schedule of theta-burst stimulation for depressive symptoms in psychiatric inpatients.
A small pilot study (n=22) will be carried out to demonstrate feasibility, using the FDA-approved stimulation site for depression treatment (L-DLPFC). Participants will be offered stimulation at the anterior cingulate cortex (ACC).
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Depression and Suicide | Device: Dorsolateral Prefrontal Cortex Accelerated Theta Burst Stimulation Device: Anterior Cingulate Cortex Accelerated Theta Burst Stimulation | Not Applicable |
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 23 participants |
| Allocation: | Non-Randomized |
| Intervention Model: | Parallel Assignment |
| Intervention Model Description: | A small pilot study (n=22) will be an open-label study in which all participants receive stimulation to the L-DLPFC to demonstrate feasibility of delivering this accelerated protocol on an inpatient unit. For participants who do not respond to L-DLPFC stimulation, we will offer an alternative site, the ACC. If patients are enrolled that have a psychiatric diagnosis other than MDD, scales measuring symptoms related to their other diagnosis/(es) will also be collected in addition to measuring change in depressive symptoms (see 'other pre-specified outcome measures' for a list of measures used to measure symptoms related to psychiatric diagnoses other than depression). |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| Official Title: | Accelerated Intermittent Theta Burst Stimulation for Depressive Symptoms |
| Actual Study Start Date : | July 1, 2018 |
| Actual Primary Completion Date : | June 1, 2020 |
| Actual Study Completion Date : | June 1, 2020 |
| Arm | Intervention/treatment |
|---|---|
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Experimental: Dorsolateral Prefrontal Cortex
The accelerated theta burst stimulation protocol will be applied to the left dorsolateral prefrontal cortex (L-DLPFC), for 10 sessions per day for up to 5 days.
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Device: Dorsolateral Prefrontal Cortex Accelerated Theta Burst Stimulation
Participants will receive iTBS (intermittent theta burst stimulation) to the left DLPFC. Stimulation intensity will be standardized at 80% of resting motor threshold (adjusted for cortical depth). Stimulation will be delivered using the Brainsway TMS system. |
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Experimental: Anterior Cingulate Cortex
The accelerated theta burst stimulation protocol will be applied to the left anterior cingulate cortex (ACC), for 10 sessions per day for up to 5 days.
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Device: Anterior Cingulate Cortex Accelerated Theta Burst Stimulation
Participants will receive iTBS (intermittent theta burst stimulation) to the anterior cingulate cortex (ACC). Stimulation intensity will be standardized at 80% of resting motor threshold (adjusted for cortical depth). Stimulation will be delivered using the Brainsway TMS system. |
- 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 (higher scores are more symptomatic).
Response is defined as a 50% reduction or greater in MADRS score compared to baseline. Remission is defined as a MADRS score of <10.
Data are presented as a raw score point change.
- 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. Higher scores indicate more suicidality.
Data are presented as a raw score point change.
- 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 (higher scores are more symptomatic).
Data are presented as a raw score point change.
- Change in Young Mania Rating Scale (YMRS) [ Time Frame: After all stimulation sessions have been completed (approximately 48 hours after the final session) ]
The Young Mania Rating Scale (YMRS) is one of the most frequently utilized rating scales to assess manic symptoms. The scale has 11 items and is based on the patient's subjective report of his or her clinical condition.
There are four items that are graded on a 0 to 8 scale (irritability, speech, thought content, and disruptive/aggressive behavior), while the remaining seven items are graded on a 0 to 4 scale. These four items are given twice the weight of the others to compensate for poor cooperation from severely ill patients.
Typical YMRS baseline scores can vary a lot. They depend on the patients' clinical features such as mania (YMRS = 12), depression (YMRS = 3), or euthymia (YMRS = 2).
Data are presented as a raw score point change.
- Change in Beck Depression Inventory II (BDI-II) [ Time Frame: After all stimulation sessions have been completed (approximately 48 hours after the final session) ]
The Beck Depression Inventory (BDI-II) is a 21-item, self-report rating inventory that measures characteristic attitudes and symptoms of depression. BDI-II items are rated on a 4-point scale ranging from 0 to 3 based on severity of each item. The maximum total score is 63.
Scores: 0-13= minimal depression, 14-19=mild depression, 20-28=moderate depression, 29-63=severe depression.
Data are presented as a raw score point change.
- 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).
Data are presented as a raw score point change.
- 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).
Data are presented as a raw score point change.
- 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.
- 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 th Quality of Life Enjoyment and Satisfaction Questionnaire-short Form Score [ 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 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
- Change in Immediate Mood Scaler (Ims-12) Depression Subscale 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 with overall score, and depression and anxiety subscales. Individual item scores range from 1-7, with a total overall score range from 12-84.
Data are presented as a raw score point change in depression subscale score. The depression subscale scores range from 7-49 (higher score indicating worse depression).
- Change in Heart Rate Variability [ 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.
Data is reported as a ratio of low frequency (LF) and high frequency (HF) (LF/HF FFT).
FFT: fast Fourier transform.
- Change in Alcohol Craving Questionnaire Score (Adapted for All Drug Use) [ Time Frame: After all stimulation sessions have been completed (approximately 48 hours after the final session) ]If participants have a co-morbid diagnosis of drug abuse this self-report questionnaire will be used to monitor craving of their particular drug of abuse.
- Change in Borderline Evaluation Of Severity Over Time (BEST) Score [ Time Frame: After all stimulation sessions have been completed (approximately 48 hours after the final session) ]If participants have a co-morbid diagnosis of borderline personality disorder this self-report questionnaire will be used to monitor symptoms.
- Change in Obsessive Compulsive Drinking Scale Score (Adapted for Use of Any Drug) [ Time Frame: After all stimulation sessions have been completed (approximately 48 hours after the final session) ]If participants have a co-morbid diagnosis of drug abuse this self-report questionnaire will be used.
- Change in Average Weekly Substance Use [ Time Frame: After all stimulation sessions have been completed (approximately 48 hours after the final session) ]If participants have a co-morbid diagnosis of drug abuse their reported average weekly substance use will be recorded.
- Change in Eating Disorder Examination Questionnaire (EDE-Q) Score [ Time Frame: After all stimulation sessions have been completed (approximately 48 hours after the final session) ]If participants have a co-morbid diagnosis of an eating disorder, this self-report questionnaire will be used to monitor symptoms.
- Change in Generalized Anxiety Disorder 7-item (GAD-7) Score [ Time Frame: After all stimulation sessions have been completed (approximately 48 hours after the final session) ]If participants have a co-morbid diagnosis of Anxiety, this self-report scale will be used to monitor anxiety symptoms.
- Change in Yale Brown Cornell Eating Disorder Scale (YBC-EDS) Score [ Time Frame: After all stimulation sessions have been completed (approximately 48 hours after the final session) ]If participants have a co-morbid diagnosis of an eating disorder, this clinician-rated assessment will be used to monitor symptoms.
- Change in Massachusetts General Hospital (MGH) Hairpulling Scale Score (Edited so Can be Used With Any Impulse Disorder) [ Time Frame: After all stimulation sessions have been completed (approximately 48 hours after the final session) ]If participants have a co-morbid diagnosis of an impulse disorder, this self-report questionnaire will be used to monitor symptoms.
- Change in Obsessive Compulsive Inventory (OCI) Score [ Time Frame: After all stimulation sessions have been completed (approximately 48 hours after the final session) ]If participants have a co-morbid diagnosis of OCD, this self-report questionnaire will be used to monitor symptoms.
- Change in Yalebrown Obsessive Compulsive Scale (YBOCS) Score [ Time Frame: After all stimulation sessions have been completed (approximately 48 hours after the final session) ]If participants have a co-morbid diagnosis of OCD, this clinician-rated scale will be used to monitor symptoms.
- Change in Numeric Rating Scale For Pain Score [ Time Frame: After all stimulation sessions have been completed (approximately 48 hours after the final session) ]If participants have a co-morbid diagnosis of a pain disorder, this rating scale will be used to monitor symptoms.
- Change in Panic Disorder Severity Scale (PDSS) Score [ Time Frame: Pre-treatment, after each day of stimulation and immediate post-treatmentAfter all stimulation sessions have been completed (approximately 48 hours after the final session) ]If participants have a co-morbid diagnosis of a panic disorder, this rating scale will be used to monitor symptoms.
- PTSD Checklist Civilian Version (PCL-C) [ Time Frame: After all stimulation sessions have been completed (approximately 48 hours after the final session) ]If participants have a co-morbid diagnosis of PTSD, this self-report questionnaire will be used to monitor symptoms.
- Change in Calgary Depression Scale For Schizophrenia (CDSS) Score [ Time Frame: After all stimulation sessions have been completed (approximately 48 hours after the final session) ]If participants have a co-morbid diagnosis of Schizophrenia, this assessment will be used to monitor symptoms.
- Change in the Positive And Negative Syndrome Scale (PANSS) Score [ Time Frame: After all stimulation sessions have been completed (approximately 48 hours after the final session) ]If participants have a co-morbid diagnosis of Schizophrenia, this clinician-rated assessment will be used to monitor symptoms.
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
| Ages Eligible for Study: | 18 Years to 85 Years (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- Over 18 years old
- Able to read, understand, and provide written, dated informed consent prior to screening. Participants will be deemed likely to comply with study protocol and communicate with study personnel about adverse events and other clinically important information.
- Currently diagnosed with Major Depressive Disorder (MDD) and/or in a current major depressive episode, according to the criteria defined in the Diagnosis and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR)
- Currently an inpatient at Stanford Hospital
- Meet the threshold on the total HAMD17 score of >/=20 at screening/baseline.
- Qualifies and has access to outpatient rTMS treatment
Exclusion Criteria:
- Any structural lesion e.g. structural neurological condition, more subcortical lesions than would be expected for age, stroke effecting stimulated area or connected areas or any other clinically significant abnormality that might affect safety, study participation, or confound interpretation of study results.
- Metal implant in brain (e.g. deep brain stimulation), cardiac pacemaker, or cochlear
- History of epilepsy/ seizures (including history of withdrawal/ provoked seizures)
- Shrapnel or any ferromagnetic item in the head
- Pregnancy
- Autism Spectrum disorder
- Active substance use (<1 week) or intoxication verified by toxicology screen--of cocaine, amphetamines, benzodiazepines
- 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
- Cognitive impairment (including dementia)
- Current severe insomnia (must sleep a minimum of 4 hours the night before stimulation)
- Current mania
- Current unmanageable psychosis
- IQ <70
- Showing symptoms of withdrawal from alcohol or benzodiazepines
- Parkinsonism or other movement d/o determined by PI to interfere with treatment
- More subcortical lesions than would be expected for age or a stroke effecting stimulated area or connected areas.
- Any other indication the PI feels would comprise data.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03601117
| United States, California | |
| Stanford Hospital | |
| Palo Alto, California, United States, 94305 | |
| Principal Investigator: | Nolan Williams, MD | Stanford University |
Documents provided by Nolan R, Stanford University:
| Responsible Party: | Nolan R, Assistant Professor, Director, Interventional Psychiatry Clinical Research, Director, Brain Stimulation Laboratory, Department of Psychiatry and Behavioral Sciences, Stanford School of Medicine, Stanford University |
| ClinicalTrials.gov Identifier: | NCT03601117 |
| Other Study ID Numbers: |
41071 |
| First Posted: | July 26, 2018 Key Record Dates |
| Results First Posted: | August 10, 2021 |
| Last Update Posted: | August 10, 2021 |
| Last Verified: | August 2021 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | No |
| Studies a U.S. FDA-regulated Drug Product: | No |
| Studies a U.S. FDA-regulated Device Product: | Yes |
| Product Manufactured in and Exported from the U.S.: | No |
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Depression Suicide Behavioral Symptoms Self-Injurious Behavior |