Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

Accelerated Intermittent Theta Burst Stimulation for Depressive Symptoms (aTBS)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT03601117
Recruitment Status : Recruiting
First Posted : July 26, 2018
Last Update Posted : June 3, 2019
Sponsor:
Information provided by (Responsible Party):
Nolan R, Stanford University

Brief Summary:
This study evaluates an accelerated schedule of theta-burst stimulation for depressive symptoms in psychiatric inpatients.

Condition or disease Intervention/treatment Phase
Depression and Suicide Device: Accelerated theta burst stimulation Not Applicable

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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 200 participants
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: None (Open Label)
Primary Purpose: Treatment
Official Title: Accelerated Intermittent Theta Burst Stimulation for Depressive Symptoms
Actual Study Start Date : July 1, 2018
Estimated Primary Completion Date : July 1, 2020
Estimated Study Completion Date : July 1, 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Suicide

Arm Intervention/treatment
Active Comparator: Dorsolateral prefrontal cortex
The accelerated theta burst stimulation protocol will be applied to the dorsolateral prefrontal cortex (dlPFC)
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.

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




Primary Outcome Measures :
  1. 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.

    Response is defined as a 50% reduction or greater in MADRS score compared to baseline. Remission is defined as a MADRS score of <10.



Secondary Outcome Measures :
  1. 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.


  2. 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.

  3. 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).


  4. 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


  5. 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).


  6. 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)


  7. 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.


  8. 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.

  9. 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.


  10. 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.


  11. 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.


  12. 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.


  13. 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).


  14. 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

  15. 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.


  16. 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

  17. 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.



Other Outcome Measures:
  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. 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.



Information from the National Library of Medicine

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.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 99 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Admitted to the psychiatric inpatient unit with a diagnosis of depressive symptoms 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:

  • 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.

Information from the National Library of Medicine

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


Contacts
Layout table for location contacts
Contact: Eleanor Cole, PhD 4157247960 ecole@stanford.edu
Contact: Romina Nejad, MSc 650-497-3933 rnejad@stanford.edu

Locations
Layout table for location information
United States, California
Stanford Hospital Recruiting
Palo Alto, California, United States, 94305
Contact: Nolan Williams, MD         
Sub-Investigator: Eleanor Cole, PhD         
Sponsors and Collaborators
Stanford University
Investigators
Layout table for investigator information
Principal Investigator: Nolan Williams, MD Stanford University

Publications:
Layout table for additonal information
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     History of Changes
Other Study ID Numbers: 41071
First Posted: July 26, 2018    Key Record Dates
Last Update Posted: June 3, 2019
Last Verified: May 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: Yes
Device Product Not Approved or Cleared by U.S. FDA: No
Pediatric Postmarket Surveillance of a Device Product: No
Product Manufactured in and Exported from the U.S.: No

Additional relevant MeSH terms:
Layout table for MeSH terms
Suicide
Depression
Self-Injurious Behavior
Behavioral Symptoms